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 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; symptom cluster; symptomatic therapy; symptomatic treatment.

Figure 1

Spasticity prevalence according to disease duration in years (N = 23,842). With permission (9).

Figure 2

Symptom reduction priorities for patients. With permission (18).

Figure 3

Areas of the CNS mediating spasticity.

Figure 4

Distribution of cannabinoid receptors (CB1 and CB2) in the central nervous system (The Endocannabinoid System). Redrawn from https://www.fundacion-canna.es/en/endocannabinoid-system. Accessed April 06, 2019). With permission.