Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study.

BACKGROUND: The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD. METHODS: This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes. RESULTS: The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab. CONCLUSION: In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.

Spontaneous Regression of Glioma-Mimicking Brainstem Lesion in a Child: A Case Report.

Differential diagnosis of focal brainstem lesions detected on MRI is challenging, especially in young children. Formerly, brainstem gliomas were classified mainly based on MRI features and location. However, since 2016, the World Health Organization's brainstem lesion classification requires tissue biopsy to reveal molecular characteristics. Although modern techniques of stereotactic or navigation-guided biopsy ensure accurate biopsy of the lesion with safety, biopsy of brainstem lesions is still generally not performed. Here, we report a focal brainstem lesion mimicking brainstem glioma in a 9-year-old girl. Initial MRI, MR spectroscopy, and 11C-methionine positron emission tomography (PET) features suggested low-grade glioma or diffuse intrinsic pontine glioma. However, repeated MR spectroscopy, perfusion MRI, and 18fluorodeoxyglucose PET findings suggested that it was more likely a non-tumorous lesion. As the patient presented not with a neurological manifestation but with precocious puberty, the attending oncologist chose to observe with regular follow-up MRI. The pontine lesion with high signal intensity on T2-weighted MRI regressed from the 6-month follow-up and became invisible on the 1.5-year follow-up MRI. We reviewed brainstem glioma-mimicking lesions in the literature and discussed the key points of differential diagnosis.

Disseminating Necrotizing Leukoencephalopathy Associated With Intra-CSF Methotrexate Chemotherapy: A Retrospective Observational Study.

BACKGROUND AND OBJECTIVES: Leptomeningeal metastases (LMs) are neoplasms that proliferate to membranes lining the brain and spinal cord. Intra-CSF methotrexate (MTX) chemotherapy is a prevalent treatment option. However, resultant long-term neurotoxicity can lead to irreversible disseminated necrotizing leukoencephalopathy (DNL). This study aims to determine the incidence, characteristics, risk factors, and outcomes of DNL following intra-CSF MTX chemotherapy for LM. METHODS: We retrospectively reviewed patients with LM who received intra-CSF MTX between 2001 and 2021 at the National Cancer Center of Korea. Patients with a follow-up duration of <3 months and those without follow-up MRI after MTX administration were excluded. The primary outcome was the development of DNL, evaluated based on the clinical and radiologic definitions of DNL. Logistic and Cox proportional regression models were used to assess the risk of DNL in patients with LM receiving intra-CSF MTX chemotherapy. RESULTS: Of the 577 patients included in the DNL investigation, 13 (2.3%) were identified to have irreversible DNL. The MRI features of DNL typically include necrotic changes in the bilateral anterior temporal region, extensive white matter, and/or brainstem lesions. All patients with DNL experienced fatal clinical course despite MTX cessation. Logistic regression analysis revealed that a cumulative dose of MTX significantly affected DNL occurrence. Multivariable analysis showed that the factor of ≥10 MTX rounds was significant for DNL development after adjusting for route of MTX administration and prior brain radiotherapy (odds ratio 7.32, 95% CI 1.42-37.77 at MTX rounds ≥10 vs < 10). In the Cox proportional hazards model considering time to occurrence of DNL, ≥10 rounds of MTX were identified as an independent predictor of DNL (hazard ratio 12.57, 95% CI 1.62-97.28, p = 0.015), even after adjusting for the synergistic effect of brain radiotherapy. DISCUSSION: DNL is a rare but fatal complication of intra-CSF MTX chemotherapy, and its progression cannot be prevented despite early recognition. The cumulative dose of intra-CSF MTX was an independent risk factor for DNL occurrence. Thus, intra-CSF MTX treatment for patients with LM should be administered with caution considering the possibility of the cumulative irreversible neurotoxicity.

Latent tuberculosis infection in Korean patients with multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: Latent tuberculosis infection (LTBI) is defined as an immune response to Mycobacterium tuberculosis infection that does not manifest clinically as active tuberculosis (TB). Since some immunotherapies can alter cellular immunity, LTBI screening has been recommended for patients with multiple sclerosis (pwMS) before initiation of long-term immunotherapies. In this study, we investigated the frequency of LTBI in Korean pwMS and patients with neuromyelitis optica spectrum disorder (pwNMOSD) and reported the long-term observation of untreated LTBI under various immunotherapies. METHODS: We enrolled pwMS or pwNMOSD who visited the Neurology department of the National Cancer Center between 2017 and 2021. LTBI was determined based on positive results of interferon-gamma release assay (IGRA) using QuantiFERON Gold Plus test and no evidence of active TB. Annual chest X-ray and careful monitoring for TB symptoms were performed until April 2023 or the time of follow-up loss. RESULTS: Among 531 patients who underwent the IGRA test, 25 pwMS (10.5%) and 42 pwNMOSD (14.3%) were diagnosed with LTBI. Of the 67 patients with LTBI, 59 patients (24 pwMS and 35 pwNMOSD) declined to receive preventive anti-TB drugs. None of the 59 with untreated LTBI demonstrated TB reactivation during 74.8 person-years in pwMS and 166.1 person-years in pwNMOSD. In addition, eight patients who completed the treatment for LTBI experienced no TB reactivation for a median of 5.5 years. CONCLUSION: The LTBI prevalence in Korean pw MS and pwNMOSD was 10.5% and 14.3%, respectively, which was much higher than that in pwMS from Western countries. Notably, none of the 59 patients with untreated LTBI showed TB reactivation over 240 person-years even under long-term immunotherapies, indicating the need for additional research to stratify the risk of LTBI-reactivation.

Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder in a paraneoplastic context.

OBJECTIVE: The association between aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and cancer via a plausible immunological response has been reported. Here, we investigated the frequency of cancer in a large cohort of patients with AQP4-IgG-NMOSD. METHODS: Between May 2005 and January 2023, patients with AQP4-IgG-NMOSD and a history of cancer were included by searching for diagnostic codes of both NMOSD and cancer in the electronic medical records and/or reviewing the database of the National Cancer Center registry of inflammatory diseases of the central nervous system. Probable paraneoplastic AQP4-IgG-NMOSD was defined according to the 2021 Criteria for Paraneoplastic Neurological Syndrome. RESULTS: Of 371 patients with AQP4-IgG-NMOSD, 23 (6.2%) had a history of cancer and four (1.1%) experienced NMOSD in a paraneoplastic context. Among the four patients with probable paraneoplastic AQP4-IgG-NMOSD, the types of cancer were lung (1 adenocarcinoma, 1 squamous cell carcinoma) and colorectal (2 adenocarcinomas). In three patients, the first NMOSD symptoms developed after a cancer diagnosis (median, 8 months [range, 4-23]), and one patient's symptoms preceded the cancer diagnosis (6 months). Compared to the 367 non-paraneoplastic patients, those in the paraneoplastic context had an older age at onset (median: 59.5 vs. 37 years, p = 0.012) and a higher proportion of longitudinally extensive transverse myelitis (LETM) as an initial manifestation (4/4[100%] vs. 130/367[35.4%], p = 0.017). CONCLUSIONS: In a large cohort of patients with AQP4-IgG-NMOSD, the frequency of cancer was low. Older age, LETM features at onset, and adenocarcinoma as the histological type were usually observed in patients with AQP4-IgG-NMOSD in a paraneoplastic context.

Validation of the International MOGAD Panel proposed criteria.

With the increased clinical interest in myelin-oligodendrocyte glycoprotein-antibody-associated disease (MOGAD), the international MOGAD panel's proposed criteria were recently released. To evaluate its diagnostic performance, the criteria were applied to a single-center cohort. Among the enrolled 100 patients, 93 fulfilled the criteria throughout the median 24 months of follow-up. All 36 patients with a clear-positive MOG-immunoglobulin G (IgG) satisfied the supporting features, except one who did not undergo magnetic resonance imaging (MRI) scan at disease onset. The criteria also contributed significantly to the confirmation of MOGAD in 57 of 64 patients without clear-positive MOG-IgG. When limited to the first attack, 51 of 61 patients (84%) satisfied the criteria, 4 of whom were initially negative for MOG-IgG. These results support the diagnostic utility of the International MOGAD Panel criteria.

Corrigendum: Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers.

[This corrects the article DOI: 10.3389/fonc.2022.942960.].

Antigen-independent IL-17A production by bystander-activated CD4+IL-1R1+ cells in patients with multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease caused by auto-antigen recognizing CD4+ T cells. However, IL-17A-producing CD4+ T cells that are bystander-activated by IL-1ß and IL-23, and T cell receptors independently, could contribute to experimental autoimmune encephalomyelitis. Here, we studied the differences in the frequency and function of bystander-activated CD4+ T cells in patients with MS. A significantly higher frequency of CD4 + IL-1Rl + T cells was found in memory than in naïve CD4+ T cells and in Th17/Th17.1 than in Th1/Th2 subtypes in both MS and healthy controls (HC). Following IL-1ß and IL-23 stimulation, IL-1Rl expression was markedly increased in both memory and Th17/Th17.1 cells, and their IL-17A-production was increased after bystander-activation, which was significantly higher in MS compared with HC. Our study suggests a potential role of IL-17A-producing bystander-activated CD4+IL-1Rl+ T cells in MS.

Severe neuromuscular immune-related adverse events of immune checkpoint inhibitors at national cancer center in Korea.

PURPOSE: Neuromuscular immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) have been increasingly recognized as a consequence of expanding use of ICIs in advanced cancers. We aimed to evaluate the frequency, phenotypes, rescue treatment, and clinical outcomes of severe neuromuscular irAEs of ICIs at National Cancer Center (NCC), Korea. MATERIALS AND METHODS: Consecutive patients with newly developed severe neuromuscular irAEs (common terminology criteria for adverse events grade 3 or greater) after ICI treatment at NCC in Korea between December 2018 and April 2022 were included by searching neuromuscular diagnostic codes in electronic medical records and/or reviewing neurological consultation documentations. RESULTS: Of the 1,503 ICI-treated patients, nine (0.6%) experienced severe neuromuscular irAEs; five with pembrolizumab and four with atezolizumab. The patients included five women and four men; their median age at onset was 59 years. The irAEs included Guillain-Barre syndrome (n = 5) and myasthenia gravis (MG) crisis with myositis (n = 4), and developed after a median of one (range 1-5) ICI cycle. The median modified Rankin score (mRS) was 4 (range 3-5) at the nadir. ICIs were discontinued in all patients, and rescue immunotherapy included corticosteroids (n = 9), intravenous immunoglobulin (n = 7), and plasmapheresis (n = 2). Eight patients showed improvements, with a median mRS of 3 (range 1-4); however, one patient (who had MG crisis with myocarditis) died. CONCLUSIONS: In this real-world monocentric study, ICI-induced neuromuscular irAEs were rare but potentially devastating; thus, physicians should remain vigilant to enable prompt recognition and management of irAEs.

Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis.

The present study aimed to evaluate whether the cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a potential prognostic marker for patients with leptomeningeal metastasis (LM). NfL levels were measured in CSF using a single-molecule array assay. A total of 42 patients with LM who were treated with ventriculo-lumbar perfusion (VLP) chemotherapy and had available stored CSF samples from the lumbar subarachnoid space before VLP chemotherapy were included in the present study, in order to investigate the prognostic value of CSF NfL. The median CSF NfL level in patients with LM was 8.15 ng/ml; 30% of patients who had died at the time of analysis had CSF NfL levels higher than the calculated overall prognostic cut-off value (11 ng/ml). The median overall survival after initiation of VLP chemotherapy was significantly longer in patients with LM and low CSF NfL levels compared with in patients with LM and high CSF NfL levels (P<0.001). The statistical significance remained after adjusting for other known prognostic factors and in a subgroup analysis according to age. In conclusion, CSF NfL could be considered a putative prognostic marker in patients with LM treated with VLP chemotherapy.

Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers.

Objective: We aimed to evaluate the potential of serum neurofilament light chain (sNfL) and serum brain-derived neurotrophic factor (sBDNF) as reliable biomarkers for paclitaxel-induced peripheral neuropathy (PIPN). Methods: Forty-eight patients with gynecologic cancer scheduled to undergo six cycles of paclitaxel-based chemotherapy at the National Cancer Center of Korea between September 2020 and January 2022 were prospectively assessed during and after chemotherapy. Results: At the end of the chemotherapy, 12 (25%) patients were classified as having grade 3 PIPN according to the National Cancer Institute-Common Toxicity Criteria. The sNfL levels increased during paclitaxel treatment in all patients. After two, four, and six cycles, patients with grade 3 PIPN exhibited higher mean sNfL levels than those in the 0-2 grade range (p = 0.004, p = 001, and p < 0.001, respectively). For sNfL levels ≥ 124 pg/mL, after two cycles of chemotherapy, the sensitivity and specificity for predicting grade 3 PIPN at the end of treatment were 80% and 79%, respectively. Over the course of paclitaxel-based treatment, sBDNF levels continued to decrease regardless of the severity of PIPN. At the end of treatment and six months after chemotherapy, patients with grade 3 PIPN had lower sBDNF levels than those within the 0-2 grade range (p =0.037 and 0.02, respectively), and the patients in the latter group had better clinical symptoms six months after the end of treatment. Conclusions: The sNfL levels during paclitaxel-based chemotherapy reflect ongoing neuroaxonal injury and serve as reliable biomarkers of PIPN severity. The sNfL levels during early treatment with paclitaxel might be prognostic indicators for PIPN progression. Low sBDNF levels 6 months after chemotherapy might adversely affect PIPN recovery.

Onset of various CNS inflammatory demyelination diseases following COVID-19 vaccinations.

BACKGROUND: Since the start of COVID-19 vaccination worldwide, there have been several reports of inflammatory demyelinating diseases of the central nervous system (CNS-IDDs) following vaccination. METHODS: We prospectively collected cases of new-onset CNS-IDDs with a temporal relationship between disease onset and COVID-19 vaccination and investigated their proportion among newly registered cases of CNS-IDD over the past year. RESULTS: Among 117 cases, 10 (8.5%) had their first disease manifestation within one month following COVID-19 vaccination: 2 multiple sclerosis, 2 neuromyelitis optica spectrum disorder, 3 MOG antibody-associated disease, and 3 unclassified CNS-IDDs. CONCLUSION: This observation suggests that COVID-19 vaccination may trigger the onset of various CNS-IDDs in susceptible individuals.

Seroprevalence of anti-myelin oligodendrocyte glycoprotein antibodies in adults with myelitis.

Although myelitis is the second most common presentation in adults with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), studies on MOG-IgG seroprevalence in patients with myelitis episodes are sparse. Herein, we investigated MOG-IgG seroprevalence in Korean adults who exhibited myelitis since 2017. Among 151 adults with acute myelitis, 11 (7.3%) tested positive for MOG-IgG by the initial screening and 10 (6.6%) patients were finally diagnosed with MOGAD during the study period. This study is the first to provide data on MOG-IgG seroprevalence in adults with myelitis and supports the clinical utility and importance of MOG-IgG testing in myelitis episodes.

Rituximab-Induced Hypogammaglobulinemia and Risk of Infection in Neuromyelitis Optica Spectrum Disorders: A 14-Year Real-Life Experience.

BACKGROUND AND OBJECTIVES: To investigate the frequency and predictors of hypogammaglobulinemia during long-term rituximab (RTX) treatment in patients with neuromyelitis optica spectrum disorder (NMOSD) and its association with infections. METHODS: We retrospectively reviewed the data of patients with NMOSD who received RTX through the maintenance regimen based on memory B-cell detection for at least 1 year from 2006 to 2021 at an institutional referral center for NMOSD. RESULTS: A total of 169 patients received a median of 10 courses (range 1-27) of RTX reinfusion after induction over a median of 8 (range, 1-15) years. Their mean serum immunoglobulin (Ig)G level began to decline significantly after 2 years of treatment, steadily declined at a rate of 2%-8% per year for the following 8 years, and then plateaued after 10 years. The proportion of patients with hypo-IgG (<6 g/L) increased from 1.2% after 1 year of treatment to 41% after 14 years of treatment. While being treated with RTX, 58 (34%) patients had 114 infections, of whom 14 (8%) patients had 15 severe infections. Multivariable logistic regression analyses identified duration of RTX treatment in years (odds ratio [OR] 1.234, 95% confidence interval [CI] 1.015-1.502), mean annual RTX dose (OR 0.063, 95% CI 0.009-0.434), history of mitoxantrone (OR 3.318, 95% CI 1.109-9.93), hypo-IgG at baseline (OR 40.552, 95% CI 3.024-543.786), and body mass index >25 kg/m2 (OR 4.798, 95% CI 1.468-15.678) as independent predictors of hypo-IgG. The risk of infection during RTX treatment was independently associated with high Expanded Disability Status Scale scores (OR 1.427, 95% CI 1.2-1.697) and relapses during RTX treatment (OR 1.665, 95% CI 1.112-2.492), but not with hypogammaglobulinemia. DISCUSSION: Over 14 years of long-term RTX treatment, IgG levels gradually decreased, and the frequency of hypo-IgG increased to 41% of the patients. Patients with prolonged memory B-cell depletion after RTX, previous mitoxantrone history, hypo-IgG at baseline, or obesity were at risk of developing RTX-induced hypogammaglobulinemia. Nevertheless, infection rates remained low during treatment, and reduced immunoglobulin levels were not associated with an increased incidence of infections.

Clinical and Radiological Features of Myelin Oligodendrocyte Glycoprotein-Associated Myelitis in Adults.

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have recently been established as a biomarker for MOG-antibody-associated disease (MOGAD), which is a distinct demyelinating disease of the central nervous system. Among the diverse clinical phenotypes of MOGAD, myelitis is the second-most-common presentation in adults, followed by optic neuritis. While some features overlap, there are multiple reports of distinctive clinical and radiological features of MOG-IgG-associated myelitis, which are useful for differentiating MOGAD from both multiple sclerosis and neuromyelitis optica spectrum disorder. In this review we summarize the clinical and radiographic characteristics of MOG-IgG-associated myelitis with a particular focus on adult patients.

Towards imaging criteria that best differentiate MS from NMOSD and MOGAD: Large multi-ethnic population and different clinical scenarios.

BACKGROUND: The "1/3″ brain magnetic resonance imaging (MRI) criteria including 1) a lesion adjacent to the lateral ventricle and in the inferior temporal lobe, or 2) a juxtacortical lesion, or 3) a Dawson finger-type lesion were shown to distinguish multiple sclerosis (MS) from antibody-mediated conditions. In this large multicentre study, we aimed to assess how the criteria perform 1) in different onset phenotypes, 2) distinct ethnic groups, 3) when the absence of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD)-typical fluffy infratentorial (FIT) lesions and longitudinally extensive transverse myelitis (LETM) lesions are added as features ("2/4″ and 3/5″ criteria, respectively). METHODS: 577 patients with MS (n = 332), aquaporin-4 antibody (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD) (n = 196) and MOGAD (n = 49) were recruited from 6 international centres (Buenos Aires, Sao Paolo, Maracaibo, Goyang, Oxford and Milan). Imaging scans were obtained at disease onset or relapse. RESULTS: Adding the absence of FIT lesions increased the specificity of the "1/3″ criteria vs. AQP4-Ab NMOSD from 84.7% to 87.2% and vs. MOGAD from 85.7% to 93.9% without compromising their sensitivity (86%). In particular, for those presenting with brain/brainstem attacks "2/4″ had significantly higher specificity than "1/3″ (85% vs. 80% against AQP4-Ab NMOSD, 88.9% vs. 72.2% against MOGAD). Positive predictive values of the "1/3″ criteria for MS were lowest for Asian patients (84.8 vs. 99.1% for White) but were significantly increased by adding further criteria (94.1% for "3/5″). CONCLUSION: The "1/3″ criteria perform well in discriminating MS from NMOSD and MOGAD regardless of ethnic background and clinical scenario. Adding the absence of FIT lesions increases the specificity in those presenting with brain/brainstem symptoms.

CSF GFAP levels in double seronegative neuromyelitis optica spectrum disorder: no evidence of astrocyte damage.

BACKGROUND: Despite rigorous confirmation with reliable assays, some individuals showing the neuromyelitis optica spectrum disorder (NMOSD) phenotype remain negative for both aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies. OBJECTIVE: We aimed to investigate whether double seronegative NMOSD (DN-NMOSD) and NMOSD with AQP4 antibody (AQP4-NMOSD) share the same pathophysiological basis, astrocytopathy, by measurement of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) levels as a marker of astrocyte damage. METHODS: Seventeen participants who (1) satisfied the 2015 diagnostic criteria for NMOSD, and (2) tested negative for AQP4 and MOG antibodies confirmed with repeated cell-based assays, and (3) had available CSF samples obtained at the point of clinical attacks, were enrolled from 4 medical centers (South Korea, Germany, Thailand, and Denmark). Thirty age-matched participants with AQP4-NMOSD, 17 participants with MOG antibody associated disease (MOGAD), and 15 participants with other neurological disorders (OND) were included as controls. The concentration of CSF GFAP was measured using enzyme-linked immunosorbent assay. RESULTS: CSF GFAP levels in the DN-NMOSD group were significantly lower than those in the AQP4-NMOSD group (median: 0.49 versus 102.9 ng/mL; p < 0.001), but similar to those in the OND (0.25 ng/mL) and MOGAD (0.39 ng/mL) control groups. The majority (90% (27/30)) of participants in the AQP4-NMOSD group showed significantly higher CSF GFAP levels than the highest level measured in the OND group, while no participant in the DN-NMOSD and MOGAD groups did. CONCLUSIONS: These results suggest that DN-NMOSD has a different underlying pathogenesis other than astrocytopathy, distinct from AQP4-NMOSD.

Absence of attack-independent neuroaxonal injury in MOG antibody-associated disease: Longitudinal assessment of serum neurofilament light chain.

To evaluate the occurrence of attack-independent neuroaxonal and astrocytic damage in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) levels were longitudinally measured in 102 sera using a single-molecule array assay. Sera from 15 adults with relapsing MOGAD with available longitudinal samples for the median 24-month follow-up and 26 age-/sex-matched healthy controls were analyzed. sNfL levels were significantly elevated in all clinical attacks, where the levels decreased below or close to cut-off value within 6 months after attacks. sNfL levels were consistently low during inter-attack periods. In contrast, sGFAP levels did not increase in most clinical attacks and remained low during follow-up. Significant neuroaxonal damage was observed at clinical attacks, while attack-independent neuroaxonal and astrocytic injury was absent in MOGAD.

Brighter spotty lesions on spinal MRI help differentiate AQP4 antibody-positive NMOSD from MOGAD.

In a large acute myelitis cohort, we aimed to determine whether brighter spotty lesions (BSLs)-using the refined terminology-on spinal magnetic resonance imaging (MRI) help distinguish aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) from myelin oligodendrocyte glycoprotein antibody disease (MOGAD). An experienced neuro-radiologist and two neurologists independently analyzed 133 spinal MRI scans (65 from MOGAD and 68 from AQP4-NMOSD) acquired within 1 month of attacks. BSLs were observed in 18 of 61 (30%) participants with AQP4-NMOSD, while none of 49 participants with MOGAD showed BSL (p < 0.001). BSL during the acute phase would be useful to differentiate AQP4-NMOSD from MOGAD.