(1) The co-occurrence of AQP4 and myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with demyelinating disorders is extremely rare. In addition, a concomitant involvement of the peripheral nervous system (PNS) has been described either in association with AQP4 antibodies-positive neuromyelitis optica spectrum disorder (NMOSD), or MOG-associated disease. We report on a case of NMOSD with co-occurrence of AQP4 and MOG antibodies and concomitant central and peripheral nervous system involvement. We also reviewed available cases of AQP4-MOG double-positive patients. (2) Brain and spine MRI, cerebrospinal fluid studies, and electrophysiological test were performed. Serum AQP4 and MOG positivity was assessed with live cell-based assay. (3) A 62-year-old woman presented with recurrent optic neuritis, myelitis, and radiculitis, tested positive for AQP4 and MOG antibodies, and was treated successfully with rituximab. (4) Although few cases of AQP4-MOG double-positive patients were already described mostly affecting females with a concomitant spinal cord and optical nerve involvement, we describe the first case of double-positive NMOSD with the peculiar involvement of both central and peripheral nervous system.

Botulinum toxin (BT) is an effective treatment for spasticity symptoms in multiple sclerosis (MS). Despite its wide use in clinical practices, only few studies have explored long-term persistence. We aim to evaluate the rate of discontinuation of BT treatment and the correlation with MS, spasticity, and injection variables. This retrospective study on 3-year prospectively collected data included 122 MS patients receiving BT injections for spasticity. We collected MS clinical variables (disease durations, Expanded Disability Status Scales [EDSSs], disease-modifying treatments [DMT], and Symbol Digit Modalities Tests [SDMTs]), modified Ashworth scales [MASs], concomitant treatments, and injection variables (formulation, dose, number of injections, and intervals between injections). A total of 14 out of the 122 patients discontinued BT after a mean time of 3.0 ± 1.5 years. In the Cox regression model including the MS clinical variables, the probability of BT discontinuations increased in patients with DMT changes during follow-ups (HR = 6.34; 95%Cl = 2.47, 18.08; p < 0.01) and with impaired SDMTs (HR = 1.20; 95%Cl = 1.04, 1.96; p < 0.01). In the model including the spasticity variables, there were no associations between BT discontinuation and MAS or other spasticity treatments. In the model including the injection variables, the probability of discontinuation decreased by 80% for each cumulative injection (HR = 0.16; 95%Cl = 0.05, 0.45; p < 0.01), but increased by 1% for each additional day over the 3-month interval between injections (HR = 1.27; 95%Cl = 1.07, 1.83; p < 0.01). BT discontinuation was associated with concomitant MS-related issues (e.g., treatment failure and DMT change) and the presence of cognitive impairment, which should be accounted for when planning injections. The interval between injections should be kept as short as possible from regulatory and clinical perspectives to maximize the response across all of the spasticity symptoms and to reduce discontinuation in the long term.

Pivotal trials showed the effectiveness of the monoclonal antibody ocrelizumab in relapsing and progressive multiple sclerosis (MS). However, data on everyday practice in MS patients and markers of treatment effectiveness are scarce. We aimed to collect real-world data from ocrelizumab-treated MS patients, relapsing-remitting (RR) and progressive MS patients (PMS), including active secondary progressive MS (aSPMS) and primary progressive MS (PPMS) patients, and to explore potential prognostic factors of clinical outcome. Patients were enrolled at MS centres in the Campania region, Italy. We collected clinic-demographic features retrospectively one year before ocrelizumab start (T₋₁), at ocrelizumab start (T₀), and after one year from ocrelizumab start (T₁). We explored possible clinical markers of treatment effectiveness in those patients receiving ocrelizumab treatment for at least one year using multilevel-mixed models. We included a total of 383 MS patients (89 RRMS and 294 PMS; 205 females, mean age: 45.8 ± 11.2, disease duration: 12.7 ± 11.6 years). Patients had a mean follow-up of 12.4 ± 8.2 months, and 217 patients completed one-year ocrelizumab treatment. Overall, EDSS increased from T₋₁ to T₀ (coeff. = 0.30, 95% coefficient interval [CI] = 0.19–0.41, p < 0.001) without a further change between T₀ and T₁ (p = 0.61). RRMS patients did not show an EDSS change between T₋₁ and T₀ nor between T₀ and T₁. Conversely, PMS patients showed EDSS increase from T₋₁ to T₀ (coeff. = 0.34, 95% CI = 0.22–0.45, p < 0.001) without a further change between T₀ and T₁ (p = 0.21). PMS patients with a time from conversion shorter than 2 years showed increased EDSS from T₋₁ to T₀ (coeff. = 0.63, 95% CI = 0.18–1.08, p = 0.006) without a further change between T₀ and T₁ (p = 0.94), whereas PMS patients with a time from conversion longer than 2 years showed increased EDSS from T₀ to T₁ (coeff. = 0.30, 95% CI = 0.11–0.49, p = 0.002). Naïve patients showed an EDSS decrease between T₀ and T₁ (coeff. = −0.30, 95% CI = −0.50–−0.09, p = 0.004). In conclusion, our study highlighted that early ocrelizumab treatment is effective in modifying the disability accrual in MS patients.

This study investigates longitudinal changes in health-related quality of life (HRQoL) in early-onset multiple sclerosis (MS) patients and explores the impact of disease activity (relapses) on such changes. People with MS (PwMS) onset between 12 and 25 years of age were followed longitudinally. At baseline and at year 4, patients were asked to fill the Paediatric Quality of life inventory (PedsQL). Demographic and clinical features were collected at both time points. Longitudinal within-group comparison of HRQoL total score and sub-scores was performed via paired samples t-test. The effect of relapses on the HRQoL changes over time was explored via linear mixed-effects analysis. No longitudinal changes were observed in the overall PedsQL score, nor in the physical, school and psychological functioning. An increase in the social functioning subscale (p < 0.001) and a decrease in the emotional subscale (p = 0.006) were observed. The change in social functioning, but not the one in the emotional subscale, was affected by the occurrence of relapses (p = 0.044). In conclusion, stimulating the patients to accept their emotional responses to health-related limitations, while preserving their social and relational resources seems key to the preservation of an adequate QoL over time in juvenile-onset MS.

Background: People with Multiple Sclerosis (MS) frequently experience cognitive impairment and neurobehavioral issues including depression and fatigue. We aim to define neuropsychological phenotypes in MS based on cognitive function, depression and fatigue.Methods: In this cross‐sectional study, we collected clinical and neuropsychological data for 600 MS patients. Neuropsychological assessments included Brief International Cognitive Assessment for MS (BICAMS), Beck Depression Inventory (BDI‐II) and Modified Fatigue Impact Scale (MFIS). We employed a latent profile analysis (LPA) to unveil latent neuropsychological profiles in MS patients, clustering individuals in unobserved groups, and we compared clinical and MRI features between groups.Results: LPA identified five neuropsychological phenotypes: Normal neuropsychological phenotype, with normal cognitive and neurobehavioral scores; Isolated cognitive impairment, showing mild reduction in BICAMS scores; Isolated neurobehavioral impairment, showing increased BDI‐II and MFIS scores; Mild neuropsychological impairment, showing mildly reduced BICAMS scores, and mildly increased BDI‐II and MFIS scores; Severe neuropsychological impairment, showing severely reduced BICAMS scores, and great increase in BDI‐II and MFIS scores vs patients with normal neuropsychological phenotype.Relapsing‐onset and paediatric‐onset patients are more likely in the normal neuropsychological phenotype and isolated cognitive impairment class. Patients with severe neuropsychological impairment showed lower cortical grey matter, thalamic, amygdala, pallidum and putamen volume compared with those with isolated neurobehavioral impairment.Conclusions: We identified five neuropsychological phenotypes in patients with MS that showed distinct clinical and radiologic features, as from different stages of the disease pathology accrual. Clinical and MRI features may help distinguishing patients requiring closer monitoring of cognitive or neurobehavioral symptoms.Disclosures: Antonio Luca Spiezia, Fabrizia Falco, Federica Lamagna, Martina Eliano, Valerio Nicolella, Antonio Esposito and Cristina Di Monaco have nothing to disclose. Marcello Moccia has received financial support by the MUR PNRR Extended Partnership (MNESYS no. PE00000006, and DHEAL‐COM no. PNC‐E3‐2022‐23,683,267); research grants from the ECTRIMS‐MAGNIMS, the UK MS Society, and Merck; salary as Assistant Editor of Neurology; and honoraria from Abbvie, Biogen, BMS Celgene, Ipsen, Jansenn, Merck, Novartis, Roche, and Sanofi‐Genzyme. Sirio Cocozza has served on scientific advisory board for Amicus Therapeutics, has received speaker honoraria from Sanofi and research grants from Fondazione Italiana Sclerosi Multipla and Telethon. Giuseppe Pontillo was supported by the MAGNIMS/ECTRIMS (2020), ESNR (2021), and ECTRIMS (2022) research fellowship programs. Roberta Lanzillo has received honoraria from Biogen, Merck, Novartis, Roche and Teva. VBM has received research grants from the Italian MS Society, and Roche, and honoraria from Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi‐ Genzyme and Teva. Vincenzo Brescia Morra has received research grants from Italian MS Federation and Roche; and honoraria from Almirall, Biogen, BMS Celgene, Janssen, Merck, Novartis, Roche, Sanofi‐Genzyme, and Viatris. Maria Petracca discloses travel/meeting expenses from Novartis, Janssen, Roche and Merck; speaking honoraria from HEALTH&LIFE S.r.l., AIM Education S.r.l., Biogen, Novartis and FARECOMUNICAZIONE E20; honoraria for consulting services and advisory board participation from Biogen; research grants from Baroni Foundation and the Italian Ministry of University and Research. Antonio Carotenuto disclosed research grants from ECTRIMS‐MAGNIMS and Almirall, travel/meeting expenses from Novartis, Janssen, Roche and Merck and speaking honoraria from Merk, BMS, Biogen, Novartis, Roche and Almirall.

Objective: We aimed to explore associations between plasma neurofilament light chain (pNfL) and cognition through patient-reported outcomes (PROs) in multiple sclerosis (MS). Methods: In this cross-sectional study, we included 211 people with MS (PwMS) and collected data from pNfL (fully automated chemiluminescent enzyme immunoassay), EDSS, education, cognition (the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT II), and Brief Visuospatial Memory Test–Revised (BVMT-R)), the Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI), and Pittsburgh Sleep Quality Index (PSQI). Results: On multivariate linear regression models, higher educational attainment was significantly associated with lower pNfL (high school: Coeff = −0.22, 95% CI = −0.41 to −0.04, p = 0.019; university: Coeff = −0.22, 95% CI = −0.42 to −0.02, p = 0.030). In logistic regression models, the likelihood of having pNfL levels above normal thresholds increased by 56% for each one-point increment in the EDSS score (OR = 1.56, 95% CI = 1.23 to 1.98, p < 0.001) and was 2.5 times greater in individuals with impaired SDMT (OR = 2.50, 95% CI = 2.20 to 5.21, p = 0.014). No statistically significant associations were observed between pNfL and CVLT-II, BVMT-R, BDI-II, MFIS, BAI, or PSQI. Conclusions: Neuro-axonal damage in people with MS manifests clinically as increased disability and reduced attention and processing speed. However, these effects may be mitigated by greater brain resilience, as suggested by the protective role of higher educational attainment. The PROs assessed in this study showed no significant associations with pNfL levels, possibly due to measurement errors and heterogeneity, with limited sensitivity to neuro-axonal damage.