Cognitive changes in early MS: A call for a common framework
Introduction
It has been accepted amongst neurologists that cognitive impairment is prevalent already at the early stages of multiple sclerosis (MS) and even when diagnosis is only probable [1]. First to be impaired are verbal memory, abstract reasoning and linguistic processes [2]. These findings are compatible with destruction related to axonal loss, and brain atrophy early in the disease course [3].
There are three major obstacles in the study of cognitive impairment in early MS: a) no universally accepted definition of the temporal phase in the disease course termed “early”, b) what constitutes cognitive impairment? and c) what tools are necessary for the assessment of cognition in early MS?
Offering concrete solutions to these obstacles will positively impact treatment and possibly outcome of MS patients. Accurate assessment of cognitive impairment already in the early stage of the disease may enable better management of patients, and the application of novel cognitive assessment tools may serve for creating significant milestones along disease progression. Moreover, agreement on the answers to these issues will enable a consensual clinical language in the field of cognition similarly to the universal use of both disease specific and general instruments, such as the expanded disability status scale (EDSS) used to assess neurological disability or the SF-36 that evaluates quality of life [4].
In the present article we shall attempt to review the existing literature relevant to the obstacles herein mentioned and to propose a framework that will serve neurologists in approaching the issue of cognitive impairment in early MS.
Section snippets
Defining “early” multiple sclerosis
The clinical definition of “early” MS has traditionally been related to the occurrence of the first neurological event suggestive of demyelination, defined by Poser et al. [5], as “probable” MS of the CPMS-C2 or CPMS-C3 type. Recently, the same clinical presentation was termed Clinically Isolated Syndrome (CIS) [6], while the introduction of the MacDonald criteria [7] ignored the time to second relapse (previously a pre-requisite for the diagnosis of “definite” MS), and put forward the concept
What constitutes cognitive impairment?
The dictionary definition of cognition relates to “…the mental process of knowing, including aspects such as awareness, perception, reasoning, and judgment” [19]. The source of the word cognition is from the Middle English “cognicioun”—to learn or to know. It is apparent from this all-encompassing definition that the sphere of cognition is composed of a large number of functions and their interactions. There is no one set of functions that is defined as “cognition” but rather their various
Choosing appropriate assessment tools
The tests employed in either screening or extensive in-depth evaluations of cognitive function in MS reflect the definition of cognitive impairment used by the researchers (Table 1). Patients seen in MS clinics and neurologic practices are not routinely assessed neuropsychologically. In part this may be due to a lack of consensus among clinicians regarding the optimal approach for evaluating cognitive impairment in MS patients. Recently, an international expert panel composed of
Commentary
Insufficient attention has been paid to the fact that MS patients in the early stage of the disease by no means constitute a uniform group. Individual patients differ from each other with regard to clinical presentation, level of disability, anatomical location and number of demyelinating lesions and severity of cognitive deficits. This heterogeneity is reflected in cognitive studies focusing on “early” MS, but in most it was not accounted for. In the present review we have tried to take into
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2018, Multiple Sclerosis and Related DisordersCitation Excerpt :These observations also support observations made in the TEMSO phase 3 trial (NCT00134563) in which teriflunomide treatment was associated with significant improvement in cognitive performance vs. placebo (Miller et al., 2011; Sprenger TSMPW et al., 2017). These observations are noteworthy, as cognitive impairment can manifest early in the MS disease course (Achiron and Barak, 2006) and impose a significant burden on patients’ quality of life and personal relationships (Cadden and Arnett, 2015), and may impact treatment adherence (McKay et al., 2017). Overall quality of life outcomes, as measured by MusiQoL and the Stern Leisure Activity Scale, remained stable in patients who switched DMT regardless of the prior DMT received.
Patient-reported outcomes in relapsing forms of MS: Real-world, global treatment experience with teriflunomide from the Teri-PRO study
2017, Multiple Sclerosis and Related DisordersCitation Excerpt :Teriflunomide treatment was previously shown to be associated with a significant improvement in cognitive performance vs placebo in the TEMSO phase 3 trial (NCT00134563), as measured by the Paced Auditory Serial Addition Test (Miller et al., 2011). Together, these observations are noteworthy because cognitive impairment can manifest early in the MS disease course (Achiron and Barak, 2006) and imposes a significant burden on patients in terms of their capacity to remain in employment, while also adversely impacting personal relationships and quality of life (Cadden and Arnett, 2015; Multiple Sclerosis International Federation, 2013). Cognitive decline in MS is also associated with other manifestations of the disease, including brain volume loss (Vollmer et al., 2016), which is known to occur at an accelerated rate in patients with MS relative to the general population (De Stefano et al., 2014).
How reliable is the classification of cognitive impairment across different criteria in early and late stages of multiple sclerosis?
2014, Journal of the Neurological SciencesThalamic atrophy and cognitive impairment in clinically isolated syndrome and multiple sclerosis
2014, Journal of the Neurological SciencesCitation Excerpt :Multiple sclerosis (MS) patients, particularly in the later stage of the disease, are known to manifest cognitive deficits [1–6].