The Broad Concept of “Spasticity-Plus Syndrome” in Multiple Sclerosis: A Possible New Concept in the Management of Multiple Sclerosis Symptoms

Abstract

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.

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

“…Workmat R is a structured discussion methodology based on the promotion of debate and sharing of clinical experience among a group of experts (24,25). Different specific exercises were designed, tested, and validated by a Scientific Committee composed of six neurologists with recognized expertise in MS spasticity management and who previously participated in the Spasticity-Plus syndrome concept definition (11).…”

“…As most MS symptomatology treatments target individual symptoms, managing them requires a multidisciplinary approach and often results in polytherapy (11). Polytherapy increases the risk of side effects and drug interactions and can exacerbate other MS symptoms (12)(13)(14).…”

“…An approach to achieve this goal is to identify symptoms that share a common underlying pathological mechanism and/or that may benefit from being treated with a single therapy. Based on this rationale, we recently defined the Spasticity-Plus syndrome concept, which encompasses a group of symptoms associated with MS spasticity with a common or close pathophysiology and/or responding to the same treatment (11). These symptoms include spasticity, spasms/cramps, pain, bladder dysfunction, fatigue, and sleep disorders (11).…”

“…Based on this rationale, we recently defined the Spasticity-Plus syndrome concept, which encompasses a group of symptoms associated with MS spasticity with a common or close pathophysiology and/or responding to the same treatment (11). These symptoms include spasticity, spasms/cramps, pain, bladder dysfunction, fatigue, and sleep disorders (11).…”

“…This symptom is characterized by muscle stiffness that can lead to pain, spasms, and reduced mobility, deeply impairing QoL (17). Moreover, the increased muscle tone can trigger or worsen non-mobility MS symptoms, such as fatigue, sleep disorders, and bladder dysfunction (17), several of them mediated in the brainstem or close areas (11). The cannabinoid receptors CB1 and CB2 are distributed across the central nervous system and are highly expressed in the brainstem (18).…”