Cognitive changes in early MS: A call for a common framework

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Abstract

Cognitive dysfunction is among the main symptoms of multiple sclerosis (MS) and adversely affects patients' quality of life. The occurrence of cognitive impairment early in the disease process raises crucial issues related to definition of the impairment and its magnitude as well as to the tools applied to the assessment. To date there is little evidence concerning the reliability and validity of cognitive measures in early MS and their predictive long-term role. As MS is a complex disease, multidimensional approaches should be further developed and validated to study the cognitive sphere in the early stages of the disease. Considering that none of the available tests performed in isolation is able to provide a complete picture of the cognitive impairment in early MS, this calls for the definition of phase duration, impairment and tools appropriate for use by clinicians and researches. The present review proposes a framework aimed to help neurologists in approaching cognitive impairment in early MS and stimulate discussions and evaluations of the suggested recommendations.

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

References (31)

  • N.I. Landro et al.

    Depressive symptoms account for deficient information processing speed but not for impaired working memory in early phase multiple sclerosis

    J Neurol Sci

    (2004)
  • L.A. Hansen et al.

    Position paper on diagnostic criteria for Alzheimer disease

    Neurobiol Aging

    (1997)
  • Y. Barak et al.

    Screening for early cognitive impairment in multiple sclerosis patients using the clock drawing test

    J Clin Neurosci

    (2002)
  • A. Achiron et al.

    Multiple sclerosis—from probable to definite diagnosis: a 7-year prospective study

    Arch Neurol

    (2000)
  • I. Grant et al.

    Deficient learning and memory in early and middle phases of multiple sclerosis

    J Neurol Neurosurg Psychiatry

    (1984)
  • N. De Stefano et al.

    Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability

    Arch Neurol

    (2001)
  • A. Leplege et al.

    Preliminary analysis of the psychometric properties of the French version of an international questionnaire measuring the quality of life: the MOS SF-36 (version 1.1)

    Rev Epidemiol Sante Publique

    (1995)
  • C.M. Poser et al.

    New diagnostic criteria for multiple sclerosis: guidelines for research protocols

    Ann Neurol

    (1983)
  • S.P. Morrissey et al.

    The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis. A 5-year follow-up study

    Brain

    (1993)
  • W.I. McDonald et al.

    Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis

    Ann Neurol

    (2001)
  • I. Grant et al.

    Deficient learning and memory in early and middle phases of multiple sclerosis

    J Neurol Neurosurg Psychiatry

    (1984)
  • A. Feinstein et al.

    Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study

    J Neurol Neurosurg Psychiatry

    (1992)
  • M.P. Amato et al.

    Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up

    Arch Neurol

    (1995)
  • L. Pelosi et al.

    Working memory impairment in early multiple sclerosis. Evidence from an event-related potential study of patients with clinically isolated myelopathy

    Brain

    (1997)
  • K. Dujardin et al.

    Attention impairment in recently diagnosed multiple sclerosis

    Eur J Neurol

    (1998)
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