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Introduction: Spasticity is a common symptom in multiple sclerosis (MS) and it is often associated with other symptoms such as spasms/cramps and pain. The concept of Spasticity-Plus syndrome takes into account that spasticity is accompanied by one or more symptoms (spasms/cramps, pain, bladder dysfunction, sleep disorders, fatigue and/or tremor). As these symptoms share a common cannabinoid control, therapy acting on cannabinoid receptors may be useful. The main study objectives were to determine the number of MS patients who met Spasticity-Plus syndrome criteria and to identify the most common symptoms., Methods: Clinical records of MS patients treated with nabiximols in a tertiary hospital from 2002 to 2022 were reviewed retrospectively., Results: Of the 73 patients included in the study, 53.4% were women, and most had secondary progressive MS (64.4%). All patients met the criteria for Spasticity-Plus syndrome: 100% had spasticity and at least another symptom. Pain was the second most common symptom (91.8%), followed by spasms/cramps (79.4%), and fatigue (76.7%). Sleep disturbances ( p  < 0.0001) and tremor ( p  < 0.027) were more frequent in patients with relapsing-remitting MS than in patients with progressive MS. No statistically significant differences were found for spasticity, pain, spasms/cramps, and fatigue between MS phenotypes. Regarding symptoms clusters, 94.4% of the patients had three or more symptoms. Spasticity was more frequently associated with pain (91.8%) and spasms/cramps (79.4%)., Conclusion: Spasticity-Plus syndrome was present in all the study population of patients with different MS phenotypes, and treated with nabiximols., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Goicochea Briceño, Higueras, Ruiz Pérez, García Domínguez, Cuello, Meldaña Rivera and Martínez Ginés.)

Background: Patient disability, relapse rate, and age are used for family planning in multiple sclerosis (MS). However, the need for more accurate biomarkers is widely recognized. We aimed to explore the influence of age on neurofilament light chain (sNfL), which reflects acute inflammation; glial fibrillary acidic protein (GFAP), associated with disability progression independent of relapses; and anti-Müllerian hormone (AMH), reflecting ovarian reserve, to provide a tailored family planning strategy., Methods: This case-control study included 95 MS patients and 61 healthy control women (HCW). sNfL and GFAP levels were measured using a sensitive single-molecule array assay. AMH levels were measured by the automated Elecsys ® Anti-Müllerian Hormone Assay., Results: We observed no significant differences in AMH values between MS patients and the control group within any of the age-matched categories. Age exhibited a negative correlation with AMH values in both groups, as expected. Nevertheless, our findings suggest a slight tendency toward reduced ovarian reserve in MS patients (rho MS patients = -0.67, p < 0.0001; rho HCW = -0.43, p = 0.0006). Interestingly, among the 76 MS participants under 40 years old, we identified ten individuals (13.1%) with AMH levels below 0.7 ng/ml, indicative of a low ovarian reserve, and an additional six individuals (7.8%) with AMH levels between 0.7 ng/ml and 0.9 ng/ml, suggesting a potential risk of premature ovarian failure. Conversely, sNfL and GFAP levels in the MS group exhibited high variability but showed no significant association with age intervals., Conclusion: We found no significant differences in AMH, sNfL or GFAP values between MS patients and the control group within any of the age-matched categories. The assessment of AMH, sNFL and GFAP levels at MS onset facilitates personalized therapeutic and family planning strategies for childbearing-age women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cuello, Meldaña Rivera, Monreal, Gómez Lozano, García Cano, García Domínguez, Fernández Velasco, Costa-Frossard França, Goicochea, Higueras, De León-Luis, Sainz De La Maza, Villarrubia, Arribas Gómez, Ruiz Perez, Martinez Ginés and Villar.)

Multiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0-5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches., Competing Interests: VM-L has received compensation for consulting services and speaking honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Roche, Terumo, Sanofi and Teva. LB-R has received compensation for consulting services and speaking honoraria from Biogen, Sanofy-Genzyme, Merck Serono, Novartis, Roche, and Teva. JC-P has received compensation for consulting services from Roche. SE-M has received compensation for consulting services and speaking honoraria from Biogen Idec, Novartis, Merck, Bayer, Sanofi-Genzyme, Roche, and Teva. JF-L has received compensation for consulting services from Roche. LF has received compensation for consulting services from Roche, Merck, Novartis and Genzyme, for speaking honoraria from Roche, Merck and Novartis, and for traveling grants from Genzyme, Roche and Novartis. YH has received compensation for consulting services from Roche and Merck, Novartis, Teva and Genzyme, for speaking, honoraria from Roche, Merck and Novartis, and for traveling grants from Merck, Genzyme, Roche and Novartis. NT has received compensation for consulting services, traveling grants and speaking honoraria from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Teva, and Roche. AV-J has received investigation grants Juan Rodes (JR16/00024) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, and has received compensation for consulting services, participation in advisory boards, and speaking honoraria from Novartis, Stendhal, Roche, Teva, Biogen, and Genzyme-Sanofi. FP-M has received compensation for consulting services and speaking honoraria from Roche, Sanofi-Genzyme y Biogen, and speaking honoraria from Novartis, Almirall and Teva., (Copyright © 2021 Meca-Lallana, Berenguer-Ruiz, Carreres-Polo, Eichau-Madueño, Ferrer-Lozano, Forero, Higueras, Téllez Lara, Vidal-Jordana and Pérez-Miralles.)