Jan Philipp Nolte

Background: The relationship between intrathecal kappa free light chain (κ‐FLC) synthesis and retinal layer atrophy in multiple sclerosis (MS) is unknown. Objective: To investigate whether the κ‐FLC index is associated with peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIPL) thickness. Methods: Patients with newly diagnosed clinically isolated syndrome or relapsing MS and available cerebrospinal fluid (CSF) analysis and optical coherence tomography (OCT) were included. Clinical and magnetic resonance imaging (MRI) data were also assessed. κ‐FLC concentrations were measured by nephelometry, and the κ‐FLC index was calculated as (CSF κ‐FLC/serum κ‐FLC)/albumin quotient. Results: A total of 100 patients at a median age of 33 (25th–75th percentile: 25–39) years and a female predominance (58%) were included. In multivariable linear regression analysis adjusted for age, sex, disease duration, number of T2‐hyperintense and number of contrast‐enhancing MRI lesions, the κ‐FLC index was associated with pRNFL (log‐transformed κ‐FLC index: β : −2.51; 95% confidence interval [CI]: −4.01, −1.01; p = 0.001) and GCIPL thinning (log‐transformed κ‐FLC index: β : −1.24, 95% CI: −2.32, −0.17; p = 0.024). Conclusions: Intrathecal plasma cell activity, as measured by the κ‐FLC index, is associated with neuroaxonal damage, as reflected by pRNFL and GCIPL atrophy.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune disease mainly driven by aquaporin-4 antibodies (AQP4-IgG). During an attack, AQP4-IgG activates the complement system, leading to astrocyte destruction, inflammation, neuronal damage, and thus devastating and often irreversible neurologic deficits. Terminal complement inhibitors such as eculizumab and ravulizumab effectively prevent relapses, yet their therapeutic potential in stopping ongoing complement-mediated injury during acute attacks remains insufficiently explored. We conducted a multinational retrospective case series across NMOSD-specialized centers in 6 countries, analyzing 33 AQP4-IgG-positive patients (mean age: 48.1 years; 28 women) treated with component 5 (C5) inhibition during or shortly after acute relapse (mean 20.1 days from symptom onset; range 2-62). Eculizumab was used in 25 patients and ravulizumab in 8. Two additional patients were excluded because of delayed treatment initiation beyond 62 days. Lesion locations included myelitis (57.6%) and optic neuritis (30.3%). Expanded Disability Status Scale scores worsened from a pre-relapse median of 0 (interquartile range [IQR] 0-2) to a nadir of 6.5 (IQR 3.5-8), improving to 3.5 (IQR 3-6.5) at 1-3 months and 2.5 (IQR 2-6) at 6 months. All patients stabilized clinically; 20 continued C5 inhibition as attack-preventing therapy. Good, moderate, and poor/absent recovery were observed in 15, 11, and 7 patients, respectively. Earlier treatment was associated with better outcomes: treatment within 21 days yielded an odds ratio of 1.58 (95% CI 0.32-8.52) for good response. Plasma exchange was administered in 57.6% and was associated with higher overall response rates, but not with good response alone. These findings highlight the potential of complement inhibition as a treatment option for acute NMOSD attacks, particularly in patients with insufficient response to standard therapies. Given the absence of clinical worsening and the encouraging course observed in most of the patients, further investigation into the role of C5 inhibition in acute attack management is warranted. This retrospective case series provides Class IV evidence that the C5 complement inhibitors eculizumab or ravulizumab may improve disability in patients with NMOSD when given during or shortly after acute relapse.

Background/Objectives: Juvenile osteochondritis dissecans (JOCD) of the knee is commonly treated using conservative or joint-preserving surgical techniques. While clinical outcomes are generally favorable, the risk of early cartilage degeneration remains unclear. Joint space width (JSW) on weight-bearing radiographs serves as an indirect marker of cartilage health. Artificial intelligence (AI)-based JSW assessment may enable sensitive and reproducible detection of early degenerative changes. Methods: This cross-sectional feasibility study included 21 skeletally immature patients treated for JOCD of the distal femur between 2002 and 2017. Treatment modalities comprised conservative management, retrograde drilling, and fragment refixation. Fully automated JSW measurements were performed on standardized anteroposterior knee radiographs using a validated AI-based software IB Lab KOALA™, Version 2.4. JSW of the affected compartment was compared with the contralateral knee and between treatment groups. Clinical outcomes were assessed using the Lysholm Knee Scoring Scale and the International Knee Documentation Committee (IKDC) score. Additionally, a systematic review of the literature on post-treatment degenerative changes following OCD therapy was conducted according to PRISMA guidelines. Results: Compared with manually reviewing images, the software IB Lab KOALA™, Version 2.4 as easy to implement. AI-based analysis revealed no significant differences in JSW between the affected and contralateral knees, nor between treatment modalities. Average JSW exceeded 6 mm in all groups after a median follow-up of 64 (min. 27, max. 177) months. Clinical scores were high and comparable across treatments. A moderate positive correlation was observed between the JSW and Lysholm score, while increasing age and longer follow-up were associated with a reduced JSW. The systematic review identified ten relevant studies, reporting generally favorable long-term clinical outcomes with a low but present risk of osteoarthritis progression. Conclusions: Our AI-based analysis showed no differences in JSW between conservative and joint-preserving surgical treatments of JOCD in the follow-up. This technology can provide a valuable tool for standardized and sensitive radiographic monitoring in young patients.

Introduction: Shared decision-making is advocated in treating patients with multiple sclerosis (pwMS), enabled by the wide range of disease-modifying treatments (DMTs). However, the role of psychological characteristics in treatment decisions remains understudied. Methods: In a prospective study, pwMS completed the Big Five Trait inventory, UPPS Impulsive Behaviour Scale and Brief COPE at treatment initiation. Associations between choosing high-efficacy DMTs (H-DMT; natalizumab, anti-CD20 monoclonal antibodies) versus low/moderate-efficacy DMTs were analysed using logistic regression, for each dimension separately, then in a multidimensional model. Propensity scoring adjusted for MS-associated determinants of DMT choice (sex, age, disease duration, prior DMT, relapse in previous year, Expanded Disability Status Scale [EDSS]). Results: Of 148 pwMS (75.7% female, age 36.5 years [SD 9], EDSS 1.0 [IQR, 0–2]) 53.4% initiated H-DMT. Higher active coping (adjusted odds ratio [aOR] 1.59, p = 0.024) and openness (aOR 1.48, p = 0.046) were significantly associated with H-DMT choice, with trends for extraversion (aOR 1.38, p = 0.097), supportive coping (aOR 1.42, p = 0.069), and higher perseverance (aOR 1.43, p = 0.068). In the multidimensional model, neuroticism demonstrated the most substantial association (aOR 2.17, p = 0.005). Conclusion: Personality structure, particularly neuroticism, active coping and openness may influence treatment decisions among pwMS.