The Broad Concept of “Spasticity- Plus Syndrome” in Multiple Sclerosis : A Possible New Concept in the Management of Multiple Sclerosis Symptoms, Óscar Fernández et al., 2020

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

Óscar Fernández, Lucienne Costa-Frossard, Marisa Martínez-Ginés, Paloma Montero, José Maria Prieto and Lluis Ramió

Frontiers in Neurology , 2020 | Volume 11 | Article 152

doi : 10.3389/fneur.2020.00152


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 CB1 and CB2 receptors in the brainstem. Nabiximols (a combination of THC and CBD oromucosal spray) interact with both CB1 and CB2 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.

Keywords : multiple sclerosis, spasticity, symptomatic therapy, symptom cluster, symptomatic treatment


In the last two decades, the availability of new disease-modifying therapies has radically changed the management of multiple sclerosis (MS) and relapsing–remitting MS in particular (1), resulting in a longer life expectancy for patients with the disease (2). Nevertheless, MS currently remains incurable and, in most patients, disability will eventually progress and they must live with the very many symptoms associated with the disease. These symptoms can have a major impact on patient’s quality of life (3) and their management is considered important, although traditionally, this area has received far less attention than diseasemodifying therapies (4).

A wide range of treatments are available to manage each of the MS symptoms (5–7). Given that different agents are used for different symptoms and a patient may have several symptoms present at the same time, many MS patients are multi-medicated, particularly as most patients will also be receiving disease-modifying therapies. This article will assess the current fragmented approaches to pharmacological management of spasticity muscle tone increase-related symptoms and their shortcomings. Given that the treatment of MS-associated muscle spasticity has been associated in a good number of clinical trials and also observational studies with the improvement of several other functions/symptoms present in MS (8), we will conceptualize, and subsequently hypothesize, about the clinical interest of introducing the more broad concept of “Spasticity-Plus Syndrome” to provide a unified framework for managing all these seemingly related functions/symptoms. By applying such a concept, it would be possible to simplify the management of symptoms associated with MS and reduce importantly the interactions and adverse effects associated with poly-medication.