MS: Clinical Features, Symptom Management, and Diagnosis

Abstract

Given its potential for diffuse dissemination throughout virtually every ­portion of the central nervous system (optic nerves, brain, and spinal cord), it is perhaps not surprising that a broad array of symptoms may be reported by patients with Multiple Sclerosis (MS). Nonetheless, the majority of patients with MS will at some point present with a stereotyped constellation of symptoms and signs constituting a first clinical “attack” of demyelination, often referred to as a Clinically Isolated Syndrome (CIS). CIS typically comprises unilateral optic neuritis, partial transverse myelitis, or a brainstem–cerebellar syndrome (see below). The majority of patients presenting with CIS will also have characteristic lesions on brain MRI not accounting for their clinical presentation and indicative of prior asymptomatic episodes of inflammatory demyelination. These patients should be managed based on their risk of having a second attack and thus converting to Relapsing–Remitting MS (RRMS), also termed Clinically Definite MS (CDMS). In the Optic Neuritis Treatment Trial (ONTT) [1], the cumulative probability of developing MS by 15 years after onset of optic neuritis was 50% (95% confidence interval, 44–56%) and strongly related to presence of lesions on the baseline non-contrast-enhanced brain (MRI). Twenty-five percent of patients with no lesions on baseline brain MRI developed MS during follow-up compared with 72% of patients with one or more lesions. In longitudinal studies of a separate cohort of CIS patients, 83% (45/54) of patients with CIS who had abnormal results on brain MRI at baseline developed CDMS after a 10-year follow-up period and baseline lesion number and lesion volume increase over the first 5 years predicted the extent of clinical disability measured by the Expanded Disability Status Scale (EDSS) at the 14-year follow-up examination [2, 3]. These findings underscore the prognostic value of MRI early in MS. Using modern imaging criteria, it is now also possible to make a diagnosis of MS prior to a second clinical attack by demonstrating new asymptomatic lesions on MRI (i.e., dissemination in time), and most disease-modifying therapies (DMTs) are utilized in both RRMS and CIS with characteristic abnormal MRI findings. In this chapter, we will discuss the signs and symptoms experienced by MS patients as well as the diagnosis and differential diagnosis of MS.