Symptomatic therapy in multiple sclerosis: a review for a multimodal approach in clinical practice

Abstract

As more investigations into factors affecting the quality of life of patients with multiple sclerosis (MS) are undertaken, it is becoming increasingly apparent that certain comorbidities and associated symptoms commonly found in these patients differ in incidence, pathophysiology and other factors compared with the general population. Many of these MS-related symptoms are frequently ignored in assessments of disease status and are often not considered to be associated with the disease. Research into how such comorbidities and symptoms can be diagnosed and treated within the MS population is lacking. This information gap adds further complexity to disease management and represents an unmet need in MS, particularly as early recognition and treatment of these conditions can improve patient outcomes. In this manuscript, we sought to review the literature on the comorbidities and symptoms of MS and to summarize the evidence for treatments that have been or may be used to alleviate them.

Keywords: clinical medicine; comorbidity; multiple sclerosis; neurology; review; signs and symptoms; therapy.

Figure 1.

Neural control of the urinary bladder. Urinary bladder control is governed by a complex neural network involving the brainstem and spinal cord. At all times, afferent signals from the bladder and urethra transmit to the lumbosacral spinal cord, mainly via the pelvic nerve but also via the hypogastric and pudendal nerves. The afferent impulses are transmitted from the spinal cord to voluntary control centres within the CNS via the dorsal and/or spinothalmic tract. Within these afferent signals, the Gracile nucleus relays to the thalamus and cortex, while the periaqueductal grey (PAG) communicates with multiple sites including the pontine micturition centre (PMC) and the thalamus. After processing of afferent signals, switching mechanism within the pons (the PMC and potentially the pontine continence centre [PCC]) and spinal cord relay appropriate efferent signals to the bladder via the parasympathetic (pelvic) nerves, sympathetic (mainly hypogastric) nerves, and somatic (pudendal) nerves. (a) Urinary filling and storage: the detrusor remains relaxed due to a lack of parasympathetic activity and the bladder outlet is closed due to excitatory sympathetic and somatic ('guarding') reflexes that stimulate tonic contraction of the internal and external urethral sphincters, respectively. The PCC has a putative role as an 'off' switch during filling and storage, directing the urethral sphincter to contract and preventing parasympathetic bladder contractions. As the bladder fills, there is a concurrent increase in afferent signals to the brainstem and spinal cord. (b) Urinary voiding (micturition): this occurs when afferent signals from the bladder exceed a certain threshold and activate the PAG, which subsequently excites the PMC to promote an efferent promicturition response. Consequently, parasympathetic activity causes the detrusor (and bladder as a whole) to contract, whilst suppression of sympathetic and somatic activity causes relaxation of the internal and external urinary sphincters, respectively.