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.

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.