Fernández Óscar, Costa-Frossard Lucienne, Martínez-Ginés Marisa, Montero Paloma, Prieto José Maria, Ramió Lluis
Biomedical Research Institute of Malaga, University of Málaga, Málaga, Spain.
Department of Neurology, Ramón y Cajal University Hospital, Madrid, Spain.
Front Neurol. 2020 Mar 17;11:152. doi: 10.3389/fneur.2020.00152. eCollection 2020.
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 and CB receptors in the brainstem. Nabiximols (a combination of THC and CBD oromucosal spray) interact with both CB and CB 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.
多发性硬化症（MS）的病理变化会逐渐影响多个中枢神经系统（CNS）区域。基于这一事实，MS会引发一系列广泛的症状。针对MS的一种症状进行对症治疗可能会导致或加重其他不良症状（用于治疗膀胱功能障碍的抗胆碱能药物会损害认知功能，许多MS药物会导致勃起功能障碍等）。适当的对症治疗是一项尚未满足的需求。几个重要的功能/症状（肌肉张力、睡眠、膀胱、疼痛）在很大程度上是由脑干介导的。大麻素受体不规则地分布于整个CNS：CB1和CB2受体在脑干中聚集。纳比西莫尔（THC和CBD的口腔黏膜喷雾剂组合）与CB1和CB2受体均相互作用。在几项使用纳比西莫尔治疗MS痉挛的临床试验中，研究人员报告称，不仅痉挛本身有所改善，而且之前提到的几种功能/症状（痉挛、抽筋、疼痛、步态、睡眠、膀胱功能、疲劳，可能还有震颤）也有所改善。通过这些间接信息，我们可以进行概念化并因此提出假设，即可能存在一种广泛的“痉挛加综合征”，除了痉挛本身外，还涉及上述提到的其他一系列症状和功能，这可能是因为在肌张力增加后它们相互关联，并且至少部分是由脑干的相同或相近区域介导的。如果这一假设成立，那么就有可能用单一疗法治疗由MS病理引起的几种与痉挛相关的症状，从而避免联合治疗产生的不必要副作用。这将在MS的对症治疗方面取得重要进展。
