Multiple Sclerosis Journal最新文献

Testing for myelin oligodendrocyte glycoprotein immunoglobulin G antibodies (MOG-IgG) is essential to the diagnosis of MOG antibody-associated disease (MOGAD). Due to its central role in the evaluation of suspected inflammatory demyelinating disease, the last 5 years has been marked by an abundance of research into MOG-IgG testing ranging from appropriate patient selection, to assay performance, to utility of serum titers as well as cerebrospinal fluid (CSF) testing. In this review, we synthesize current knowledge pertaining to the "who, what, where, when, why, and how" of MOG-IgG testing, with the aim of facilitating accurate MOGAD diagnosis in clinical practice.

Eculizumab proved a strong anti-inflammatory effect in neuromyelitis optica spectrum disorders (NMOSD), rare autoimmune diseases affecting the central nervous system in which aquaporin 4-immunoglobulin G (AQP4-IgG) is the main pathogenic antibody. Pregnancy in NMOSD patients is considered at high-risk for neurological and gynecological outcomes, requiring a careful consideration about treatment maintenance. In this case report, we describe a successful pregnancy, resulting in the birth of a healthy child, in a young woman with AQP4-IgG-seropositive NMOSD who was maintained on eculizumab during all pregnancy.

Background: Biomarkers are needed to track progression in MS trials. Neurofilament heavy chain (NfH) has been underutilized due to assay limitations.

Objective: To investigate the added value of cerebrospinal fluid (CSF) NfH in secondary progressive multiple sclerosis (SPMS) using contemporary immunoassays.

Methods: This exploratory study was part of the MS-SMART trial. Clinical assessments (including expanded disability status scale, upper and lower limb function, visual acuity and symbol digit modalities test (SDMT)), CSF and serum sampling were acquired at baseline (n = 54), 48 and 96 weeks. Brain magnetic resonance imagings (MRIs) were obtained at baseline and 96 weeks. The NfL and NfH were measured using single-molecule array assay.

Results: Baseline CSF NfH and NfL correlated with information processing speed at 96 weeks, with CSF NfH showing stronger correlations (r = -0.49 for SDMT) than CSF NfL (r = -0.37 for SDMT). Baseline CSF NfL predicted poorer hand dexterity at baseline, 48 and 96 weeks. CSF NfH was the only predictor of cortical grey matter at baseline, while baseline CSF NfL was the only predictor of brain atrophy at 96 weeks. Serum neurofilaments showed limited associations.

Conclusion: CSF neurofilaments are better outcomes than serum neurofilaments in small SPMS studies. CSF NfH and NfL variably predict worsening hand function, information processing speed and brain volume loss, possibly reflecting complementary aspects of neurodegeneration.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder that occurs in children and adults.

Case: We report a case of a 10-year-old female with AQP4+ NMOSD who presented with paraparesis from longitudinally extensive transverse myelitis (LETM) from C2 to the conus medullaris. The patient showed gradual improvement in strength and sensation with solumedrol and plasma exchange therapy. Given her severe presentation, eculizumab therapy was also initiated acutely. She had near complete recovery, although she developed a myelitis relapse during transition to rituximab treatment.

Conclusion: This case demonstrates the role of eculizumab as a safe and effective treatment option in treating an acute attack of pediatric AQP4+ NMOSD. More data are needed to understand the risk of relapse if transitioning off of these highly effective medications.

Background: Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women.

Objective: Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS).

Methods: In pwMS and age- and sex-matched controls, upper cervical SC area from brain MRI (UCC_brain) was obtained. Impact of sex and menopause on UCC_brain (adjusted for total intracranial volume) and its association with progression and disability, including MS functional composite (MSFC), were investigated.

Results: UCC_brain was smaller in pwMS (n = 118, 51.4 ± 5.3 mm²) than controls (n = 118, 54.2 ± 4.4 mm², p < 0.001) and inversely correlated with older age in pwMS (r = -0.24, p = 0.010) but not in controls (r = -0.025, p = 0.786). In 173 pwMS (413 brain MRIs), UCC_brain was smaller in men (49.5 ± 5.9 mm²) than women (51.6 ± 5.5 mm², p = 0.001), postmenopausal women (49.4 ± 5.6 mm²) than premenopausal women (52.9 ± 4.1 mm², p < 0.001), and progressive (47.5 ± 5.6 mm²) than relapsing MS (52.1 ± 5.2 mm², p < 0.001). UCC_brain also correlated with disease duration (r = -0.39, p < 0.001), 9-hole peg test (r = -0.26, p = 0.005), and severe ambulatory disability (Expanded Disability Status Scale ⩾6) (r = -0.27, p < 0.001).

Conclusion: UCC_brain, a biomarker of progressive MS, is inversely associated with age, disease duration, male sex, and menopause, highlighting the potential impact of sex and hormones on neurodegeneration in MS.

Radiologically isolated syndrome (RIS) is the earliest documented stage in the disease continuum of multiple sclerosis (MS). It is discovered incidentally in individuals who are asymptomatic but have typical lesions in the brain or spinal cord suggestive of autoimmune inflammatory demyelination. The revised 2023 RIS criteria aim to secure an accurate and timely diagnosis due to the presence of imaging mimics. These criteria require having at least one T2-weighted hyperintense lesion in one of the four suggestive MS locations along with two of the following three features: spinal cord lesion, cerebrospinal fluid (CSF)-restricted oligoclonal bands, or new T2 or gadolinium-enhancing lesion observed on a subsequent magnetic resonance imaging (MRI) study. Once the diagnosis is confirmed, established risk factors, including age, lesion location and CSF, significantly improve prognostic stratification, which is crucial for immunoactive interventions. Recent clinical trials have shown that oral disease-modifying treatments can delay or prevent the first clinical event in RIS patients. Consulting with an MS team for each RIS case is strongly recommended to enhance care and disease surveillance. The revised 2024 McDonald criteria will classify individuals with additional CSF and advanced MRI biomarkers as having preclinical MS, highlighting the importance of vigilance in this area.

Background: Paramagnetic rim lesions (PRLs) are a magnetic resonance imaging (MRI) marker of compartmentalized intraparenchymal inflammation.

Objectives: The primary objective was to investigate clinical, demographic, and MRI factors that may be predictive of the future formation of PRL.

Methods: This is a retrospective analysis of longitudinal data. Patients were included if they had ⩾1 gadolinium-enhancing lesion on any historical MRI and follow-up scan(s) ⩾6 months afterward on a standardized 3T MRI using the filtered phase component of a susceptibility-sensitive sequence ("SWAN"). Regression and machine-learning models were used to identify the predictive ability of demographic, clinical, immunological, treatment-related, and MRI predictors of PRL formation.

Results: A total of 64 patients having 229 contrast-enhancing lesions (CELs) were included. Among all predictors, the diameter of the initial enhancing lesion was the most influential for determining subsequent PRL formation; every millimeter increase in diameter increased the risk of PRL formation by 44%. Other factors did not contribute additional information; the administration of steroids was not associated with any effect.

Conclusions: The long-axis diameter of a CEL is the best translational predictor of subsequent PRL formation at follow-up. This measure holds promise as a method to identify patients at high risk of chronic active lesion formation during the acute inflammatory window.

Background: Pain is a common symptom of multiple sclerosis (MS). The reliability of outcome measures for pain and the accuracy of screening tools are essential for treatment purposes.

Objectives: This study investigated the test-retest reliability of Neuropathic Pain Scale (NPS), Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory-Short Form (BPI-SF), Nordic Musculoskeletal Questionnaire (NMQ), Douleur Neuropathique 4 (DN4), and painDETECT, and the accuracy of DN4 and painDETECT.

Methods: 110 persons with MS were included (mean age: 45.35 ± 12.73; Expanded Disability Status Scale (EDSS): 3 (Interquartile range, IQR: 2.6)). The reliability (internal consistency, test-retest, measurement error) and accuracy (area under the curve (AUC), specificity, sensitivity, positive predictive value, and negative predictive value) were analyzed.

Results: All included pain assessment tools showed good test-retest reliability (Intraclass correlation coefficient, ICC, (95% confidence interval, CI): 0.85 (0.79-0.89)-0.89 (0.84-0.92)) and good-to-excellent internal consistency (Cronbach's α: 0.73-0.93). The test-retest reliability of NMQ was moderate to substantial (Cohen's κ = 0.54-0.87). The overall accuracy of DN4 compared to the neurologist's diagnosis was acceptable (AUC = 0.762), while that of painDETECT was poor (AUC = 0.682) and demonstrated inadequate predictive ability.

Conclusion: All pain outcome measures were reliable in patients with MS (pwMS). DN4 can be used to screen neuropathic pain in MS.

Clinical trial registry name: Reliability and Validity of Outcome Measures for Pain in MS https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CRMD&selectaction=Edit&uid=U0006NAA&ts=2&cx=-jzvd6m Registration number: NCT05742152.