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Introduction: The Spasticity-Plus Syndrome (SPS) in multiple sclerosis (MS) refers to a combination of spasticity and other signs/symptoms such as spasms, cramps, bladder dysfunction, tremor, sleep disorder, pain, and fatigue. The main purpose is to develop a user-friendly tool that could help neurologists to detect SPS in MS patients as soon as possible., Methods: A survey research based on a conjoint analysis approach was used. An orthogonal factorial design was employed to form 12 patient profiles combining, at random, the eight principal SPS signs/symptoms. Expert neurologists evaluated in a survey and a logistic regression model determined the weight of each SPS sign/symptom, classifying profiles as SPS or not., Results: 72 neurologists participated in the survey answering the conjoint exercise. Logistic regression results of the survey showed the relative contribution of each sign/symptom to the classification as SPS. Spasticity was the most influential sign, followed by spasms, tremor, cramps, and bladder dysfunction. The goodness of fit of the model was appropriate (AUC = 0.816). Concordance between the experts' evaluation vs. model estimation showed strong Pearson's ( r  = 0.936) and Spearman's ( r  = 0.893) correlation coefficients. The application of the algorithm provides with a probability of showing SPS and the following ranges are proposed to interpret the results: high (> 60%), moderate (30-60%), or low (< 30%) probability of SPS., Discussion: This study offers an algorithmic tool to help healthcare professionals to identify SPS in MS patients. The use of this tool could simplify the management of SPS, reducing side effects related with polypharmacotherapy., Competing Interests: ÓF has received honoraria in the past as consultant in advisory boards, and as chairmen or lecturer in meetings, and has also participated or participates at present in clinical trials and other research projects promoted by Biogen, Bayer, Merck-Serono, Teva, Novartis, Actelion, Almirall, Roche, Allergan, Horizon, and Ala Diagnostics. LC-F has served at scientific advisory boards, participated in meetings sponsored by and received speaking honoraria or travel funding or research grants from Biogen, Bristol-Myers Squibb, Janssen, Horizon, Merck-Serono, Novartis, Roche and Sanofi. MM has received honoraria as speaker, consultant in advisory boards, travel support or research grants from Merck, Biogen, Novartis, Sanofi-Genzyme, Almirall, Viatris, Horizon, Bristol-Myers Squibb, Roche, Sandoz and Janssen. PM has received compensation for consulting services and speaking fees from Allergan, Almirall, Biogen, Merz and Sanofi. JP has served as consultant, speaker and/or moderator for Bayer Pharmaceuticals, Biogen, Bristol-Myers Squibb, Daiichi Sankyo, Genzyme Corporation, Janssen, Merck Serono, Novartis, Sanofi, Sandoz, Teva, Roche Pharma, Almirall and Celgene. LR-T has received compensation for consulting services and speaking fees from Biogen, Novartis, Bayer, Merck, Sanofi, Genzyme, Roche, Bristol-Myers Squibb, Teva and Janssen. AM has received honoraria for scientific and commercial activities from Biogen, Teva, Merck, Sanofi, Novartis, Roche, Almirall, and Mylan. YA has received research grants, travel support and lecturing and consulting fees from Bayer, Biogen, Roche, Merck, Novartis, Almirall, Sanofi-Genzyme, Janssen and Bristol-Myers Squibb. AA has received honoraria as a speaker or advisor from Almirall, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche and Sanofi. EÁ has received collaborations and fees for participation in advisories, scientific and educational activities from Almirall, Biogen, Janssen Cilag, Sanofi-Genzyme, Merck, Novartis, Roche and Teva. AL-F reports no disclosures relevant to the manuscript. LL has received collaborations and fees for participation in advisories, scientific and educational activities, from Almirall, Bayer, Biogen, Bristol-Myers Squibb, Sanofi-Genzyme, Merck, Novartis, UCB Pharma, Roche and Teva. EM has received honoraria as consultant in advisory boards, and or as chairperson or lecturer in meetings, attendance to congresses and has also participated in clinical trials and other research projects promoted by Almirall, Bayer, Biogen, Bristol Myers Squibb, Janssen, Merck, Teva, Novartis, Roche, Sandoz and Sanofi-Genzyme. PO-N has received collaborations and fees for participation in advisories, scientific and educational activities from Almirall, Biogen, Bristol-Myers Squibb, Sanofi-Genzyme, Merck, Novartis, UCB Pharma, Roche and Teva., (Copyright © 2024 Fernández Fernández, Costa-Frossard, Martínez Ginés, Montero Escribano, Prieto González, Ramió-Torrentà, Aladro, Alonso Torres, Álvarez Rodríguez, Labiano-Fontcuberta, Landete Pascual, Miralles Martínez, Moral Torres and Oliva-Nacarino.)

Background: Early identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) can be challenging for clinicians, as diagnostic criteria for SPMS are primarily based on physical disability and a holistic interpretation., Objective: To establish a consensus on patient monitoring to identify promptly disease progression and the most useful clinical and paraclinical variables for early identification of disease progression in MS., Methods: A RAND/UCLA Appropriateness Method was used to establish the level of agreement among a panel of 15 medical experts in MS. Eighty-three items were circulated to the experts for confidential rating of the grade of agreement and recommendation. Consensus was defined when ≥66% agreement or disagreement was achieved., Results: Consensus was reached in 72 out of 83 items (86.7%). The items addressed frequency of follow-up visits, definition of progression, identification of clinical, cognitive, and radiological assessments as variables of suspected or confirmed SPMS diagnosis, the need for more accurate assessment tools, and the use of promising molecular and imaging biomarkers to predict disease progression and/or diagnose SPMS., Conclusion: Consensus achieved on these topics could guide neurologists to identify earlier disease progression and to plan targeted clinical and therapeutic interventions during the earliest stages of SPMS., Competing Interests: The authors declare the following potential conflicts of interest regarding the research, authorship, and/or publication of this article: JM-L has received grants and consulting or speaking fees from Almirall, Biogen Idec, Celgene, Genzyme, Merck, Novartis, Roche, and Teva. BC has received research support or personal compensation from any commercial entity (for-profit business) for employment, consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Sanofi, Roche, Merck, Teva, Novartis, Celgene, and Almirall. AR-A has received personal compensation from any commercial entity (for-profit business) for serving on a scientific advisory board or speaking from Merck, Biogen Idec, Roche, Genzyme, Teva, Mylan, and Celgene. SE has received speaker honoraria and consultant fees from Biogen, Novartis, Sanofi Genzyme, Merck, Almirall, Roche, and Teva. GI has received speaking and/or advisory board honoraria from Bayer, Biogen Idec, Novartis, Sanofi, Merck Serono, Almirall, Roche, Actelion, Celgene, and Teva. CD has received speaking and/or advisory board honoraria from Sanofi, Novartis, AbbVie, and Bial. JR has received speaking honoraria and personal compensation for participating on advisory boards from Biogen Idec, Genzyme, Merck Serono, Novartis, Teva, and Sanofi-Aventis. MH has received research support or personal compensation from any commercial entity (for-profit business) for employment, consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Novartis, Roche, Merck, Teva, and Genzyme-Sanofi. CC has received personal compensation from any commercial entity (for-profit business) for employment, consulting, serving on a scientific advisory board, speaking, or other activities from Teva, Sanofi-Genzyme, Merck, Novartis, Biogen, and Roche. JP-G is a consultant for Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva, Roche, and Almirall. He has participated as a speaker/moderator in meetings and/or symposia organized by Almirall, Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva, and Roche. He has received grants for research projects from Almirall, Biogen Idec, Novartis, and Sanofi-Genzyme. JA has received honoraria for lecturing, travel expenses for attending meetings, or financial support for research from Biogen Idec, Merck Serono, Genzyme, and Novartis. DU has received honoraria for lecturing, courses, advisory boards, or financial support for research from Biogen, Merck, Novartis, Roche, Sanofi, Teva, Bayer, and Almirall. LC-F has received honoraria for lecturing, travel expenses for attending meetings, or financial support for research from Merck, Bayer, Biogen, Novartis, Sanofi-Genzyme, Almirall, Roche, Celgene, Biopas, Ipsen, and Teva. AG-M has received compensation for lecturing, scientific advisory board and consulting from Novartis, Merck, Roche, Emerald, Biogen and Sanofi, and research support from Teva. CO-G has received honoraria for speaking and/or consultancy from Biogen, Sanofi-Genzyme, Merck, Roche, Teva, and Novartis., (Copyright © 2022 Meca-Lallana, Casanova, Rodríguez-Antigüedad, Eichau, Izquierdo, Durán, Río, Hernández, Calles, Prieto-González, Ara, Uría, Costa-Frossard, García-Merino and Oreja-Guevara.)

Background: Multiple sclerosis (MS) treatment has radically improved over the last years; however, MS symptom management is still challenging. The novel Spasticity-Plus syndrome was conceptualized to frame several spasticity-related symptoms that can be addressed together with broad-spectrum medication, such as certain cannabinoid-based drugs. The aim of this project was to gain insight into Spanish neurologists' clinical experience on MS spasticity and associated symptoms, and to assess the acknowledgment and applicability of the Spasticity-Plus syndrome concept in patients with MS. Methods: Ten online meetings were conducted using the Workmat ® methodology to allow structured discussions. Fifty-five Spanish neurologists, experts in MS management, completed and discussed a set of predefined exercises comprising MS symptom assessment and its management in clinical practice, MS symptoms clustering in clinical practice, and their perception of the Spasticity-Plus syndrome concept. This document presents the quantitative and qualitative results of these discussions. Results: The specialists considered that polytherapy is a common concern in MS and that simplifying the management of MS spasticity and associated manifestations could be useful. They generally agreed that MS spasticity should be diagnosed before moderate or severe forms appear. According to the neurologists' clinical experience, symptoms commonly associated with MS spasticity included spasms/cramps (100% of the specialists), pain (85%), bladder dysfunction (62%), bowel dysfunction (42%), sleep disorders (42%), and sexual dysfunction (40%). The multiple correspondence analysis revealed two main symptom clusters: spasticity-spasms/cramps-pain, and ataxia-instability-vertigo. Twelve out of 16 symptoms (75%) were scored >7 in a 0-10 QoL impact scale by the specialists, representing a moderate-high impact. The MS specialists considered that pain, spasticity, spasms/cramps, bladder dysfunction, and depression should be a treatment priority given their frequency and chance of therapeutic success. The neurologists agreed on the usefulness of the new Spasticity-Plus syndrome concept to manage spasticity and associated symptoms together, and their experience with treatments targeting the cannabinoid system was satisfactory. Conclusions: The applicability of the new concept of Spasticity-Plus in MS clinical practice seems possible and may lead to an integrated management of several MS symptoms, thus reducing the treatment burden of disease symptoms., Competing Interests: The study was funded by an investigational grant from Almirall SA. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors' views and opinions are not necessarily aligned with those of Almirall SA. OF has received honoraria as consultant in advisory boards, as chair/lecturer in meetings, and from participation in clinical trials and other research projects promoted by Actelion, Allergan, Almirall, Bayer-Schering, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Orizon, Roche, and Teva. LC-F has received honoraria as consultant in advisory boards, travel support, and speaker fees and from participation in clinical trials and other research projects promoted by Almirall, Bayer, Biogen-Idec, Biopas, Bristol Myers Squibb, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. MM-G has received compensation for consulting services and speaking fees and from participation in clinical trials from Almirall, Bayer-Schering, Biogen-Idec, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. PM has received honoraria as consultant in advisory boards, travel support, and speaker fees and from participation in clinical trials and other research projects promoted by Allergan, Almirall, Biogen-Idec, Merck-Serono, Merz, Sanofi-Genzyme and, Teva. JP-G has received honoraria as consultant for Bayer Pharmaceuticals, Biogen Spain S.L., Genzyme Corporation, Merck Serono, Novartis Pharmaceuticals Corporation, Sanofi, Teva Pharmaceutical Industries, Roche Pharma, Almirall Prodesfarma S.A., and Celgene España S.L. JP-G has participated as lecturer/moderator at meetings and/or symposia organized by Almirall Prodesfarma S.A., Bayer Pharmaceuticals, Biogen Spain S.L., Genzyme Corporation, Merck Serono, Novartis Pharmaceuticals Corporation, Sanofi, Teva Pharmaceutical Industries, and Roche Pharma. JP-G has received funding for research projects from Almirall Prodesfarma S.A., Biogen Spain S.L., Novartis Pharmaceutical Corporation, Teva Pharmaceutical Industries, and Sanofi. LR-T has received honoraria as consultant in advisory boards, as chair/lecturer in meetings, and from participation in clinical trials and other research projects promoted by Almirall, Bayer, Biogen-Idec, Sanofi, Genzyme, Merck, Novartis, Roche, Bristol-Myers, and Teva., (Copyright © 2021 Fernandez, Costa-Frossard, Martínez-Ginés, Montero, Prieto-González and Ramió-Torrentà.)

Multiple sclerosis (MS) pathology progressively affects multiple central nervous system (CNS) areas. Due to this fact, MS produces a wide array of symptoms. Symptomatic therapy of one MS symptom can cause or worsen other unwanted symptoms (anticholinergics used for bladder dysfunction produce impairment of cognition, many MS drugs produce erectile dysfunction, etc.). Appropriate symptomatic therapy is an unmet need. Several important functions/symptoms (muscle tone, sleep, bladder, pain) are mediated, in great part, in the brainstem. Cannabinoid receptors are distributed throughout the CNS irregularly: There is an accumulation of CB 1 and CB 2 receptors in the brainstem. Nabiximols (a combination of THC and CBD oromucosal spray) interact with both CB 1 and CB 2 receptors. In several clinical trials with Nabiximols for MS spasticity, the investigators report improvement not only in spasticity itself, but also in several functions/symptoms mentioned before (spasms, cramps, pain, gait, sleep, bladder function, fatigue, and possibly tremor). We can conceptualize and, therefore, hypothesize, through this indirect information, that it could be considered the existence of a broad "Spasticity-Plus Syndrome" that involves, a cluster of symptoms apart from spasticity itself, the rest of the mentioned functions/symptoms, probably because they are interlinked after the increase of muscle tone and mediated, at least in part, in the same or close areas of the brainstem. If this holds true, there exists the possibility to treat several spasticity-related symptoms induced by MS pathology with a single therapy, which would permit to avoid the unnecessary adverse effects produced by polytherapy. This would result in an important advance in the symptomatic management of MS., (Copyright © 2020 Fernández, Costa-Frossard, Martínez-Ginés, Montero, Prieto and Ramió.)