Integrated Management of Multiple Sclerosis Spasticity and Associated Symptoms Using the Spasticity-Plus Syndrome Concept: Results of a Structured Specialists' Discussion Using the Workmat® Methodology

Abstract

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.

A real‐world evidence study of nabiximols in multiple sclerosis patients with resistant spasticity: Analysis in relation to the newly described ‘spasticity‐plus syndrome’

“…It is interesting to consider that even patients whose skeletal muscle rigidity does not improve to the ≥20% or ≥30% threshold can experience improvement in MS spasticity‐related symptoms. Future investigations of nabiximols might consider evaluating progress with reference to the broader spasticity‐plus syndrome, which encompasses evolution in all MS spasticity‐associated symptoms [10, 11] rather than the single symptom of spasticity. Moreover, nabiximols‐related improvement of associated symptoms soon after treatment initiation may facilitate dose adjustments (reduction or discontinuation) of concomitant medications specifically targeting other spasticity‐associated symptoms, for example, oxybutynin for bladder dysfunction, although this requires confirmation in well‐controlled clinical trials.…”

“…The traditional approach to management of MS-related symptoms has been 'organ-oriented', aiming to resolve complications at a local level, for example, muscle relaxants for spasticity, gabapentin and other agents for pain relief, and anticholinergics for bladder dysfunction [8,9]. However, because an excess of medication can lead to interactions and intolerable adverse events, effective symptom management in MS continues to be an unmet need [10,11]. The mediation of many MS symptoms in the brainstem, where there is also a high concentration of endocannabinoid receptors [10], points to a role for cannabinoids in symptom management.…”

“…European guidelines reflect the positioning of nabiximols for symptomatic management of MS spasticity [15–18]. Evidence that nabiximols can ameliorate simultaneously occurring MS spasticity‐related symptoms would not only support the concept of the recently described ‘spasticity‐plus syndrome’ [10, 11], but also simplify the approach to symptomatic management of MS patients in daily practice, potentially reducing the risks associated with polypharmacy [19].…”

A post hoc evaluation of the shift in spasticity category in individuals with multiple sclerosis-related spasticity treated with nabiximols

“…1,2 As MS progresses over time, the prevalence and severity of MSS can worsen. 3 Spasticity and its associated symptoms, which often include spasms, mobility limitations, bladder dysfunction, sleep impairment, fatigue, sexual dysfunction and/or pain, 4 are known to reduce the quality of life (QoL) 5 of people living with MS.…”

Clinical insights on the spasticity-plus syndrome in multiple sclerosis

“…Published papers on the SPS consider cannabinoidbased medicines, more specifically nabiximols, as the optimal symptomatic therapy for treating the SPS(2)(3)(4). Cannabinoid receptors 1 and 2 are abundant in the CNS, with a higher concentration in the brainstem(2,3).…”