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This site is intended for US Healthcare Professionals only.

Introduction

Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system (CNS). MS is an inflammatory autoimmune disease that damages the myelinated axons in the CNS, resulting in the myelin being fragmented and leading to exposed axons. While the disease course of MS has high variability and is unpredictable, for most patients the disease begins with episodes of reversible neurological deficits, and is then frequently followed by progressive neurological deterioration over time.1

Overview

Although the etiology of MS is not well understood, environmental, genetic, metabolic, and immunological factors are thought to have a role. The cardinal pathological features of MS are plaques in the CNS composed of inflammatory cells, demyelinated and transected axons, reduced oligodendrocyte numbers, and gliosis. A wide range of neurological symptoms that arise from various areas of the CNS are the result of these pathological changes.2

Goals of therapy for MS include slowing disease progression, and managing relapses and symptoms.3 Treatment paradigms are evolving from traditional fixed approaches to individualized plans.4

Immune and gilal cell subtypes and their contributions to the pathogenesis of MS

Immune and glial cell subtypes and their contributions to the pathogenesis of MS2
http://www.creativecommons.org/licenses/by/4.0/

Signs & Symptoms

Signs and symptoms of MS can vary greatly between patients and over time, depending on the extent and location of myelin damage. More common symptoms of MS include:5,6

  • Difficulties walking
  • Fatigue
  • Numbness or tingling
  • Spasticity
  • Muscle weakness
  • Visual problems
  • Dizziness
  • Sexual problems
  • Bladder and bowel problems
  • Pain and itching
  • Cognitive and emotional changes

Patients with relapsing-remitting MS (RRMS), the most common disease course, experience periods of relapse during which new or recurring symptoms develop over days or weeks. These exacerbations alternate with periods of remission during which patients partially or completely recover. Patients with primary-progressive or secondary-progressive MS, however, experience more steady progression of disease, often accompanied by problems with mobility and gait.6,7

Risk Factors

These factors may increase a person’s risk of developing MS.6,8

  • Women are 2 to 3 times more likely to get MS than men.
  • MS is not directly hereditary, although genetic susceptibility plays a part in its development.
  • MS can arise at any age, but is most commonly diagnosed between 20 and 50 years of age.
  • MS occurs in just about all ethnic groups, but people of Northern European descent have the highest risk of developing MS.
  • Infections such as Epstein–Barr virus (EBV) infection may trigger MS.
  • Low levels of vitamin D and lack of sun exposure may play a role in the development of MS.

Disease & Clinical Trial Tools

There are many assessment tools which may help clinicians better document and manage their MS patients' symptoms. While the list below is not intended to be comprehensive, it represents many of the tools commonly used in rehabilitation assessment of patients with MS.

Expanded Disability Status Scale (EDSS)

The Expanded Disability Status Scale (EDSS) is used to rate neurologic impairment in MS. The EDSS total score ranges from 0 to 10, with scores below 4.5 reflecting a high degree of ambulatory ability and progressively higher scores reflecting loss of ambulatory ability.

Functional system (FS) grades are key to the EDSS, especially within the lower scores of the scale. The eight functional systems assessed are pyramidal, cerebellar, brain stem, sensory, bowel and bladder, visual (or optic), cerebral (or mental), and other. Each system is graded on a scale of 0 to 5 or 6, with 0 representing normal function. The only exception is the “other” system, which shows the presence or absence of other neurologic findings attributed to MS through a grade of 1 or 0, respectively.

The EDSS score is determined through the evaluation of FS grades and ambulatory ability, as presented in the table.9

Download EDSS

Multiple Sclerosis Quality of Life-54 (MSQOL-54)10

Multiple Sclerosis Quality of Life-54 (MSQOL-54) measures health-related quality of life (HRQOL) in MS patients through self-reported scoring of 54 items. Of these items, 52 assess 12 dimensions of HRQOL, including physical function, role limitations (physical), role limitations (emotional), pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. The remaining two items assess change in health status and satisfaction with sexual function.

Items are then averaged within related categories to produce associated scale scores with values ranging from 0-100; higher values indicate better quality of life. Weighted combinations of scale scores create two composite scores, physical health and mental health, as shown in the tables.

Download MSQOL-54

Multiple Sclerosis Functional Composite (MSFC)

The Multiple Sclerosis Functional Composite (MSFC) is a clinical outcome measure that assesses arm, leg, and cognitive function through the use of the nine-hole peg test (9HPT), timed 25-foot walk (T25FW), and 3-minute Paced Auditory Serial Addition Test (PASAT-3), respectively.11

The following components compose the MSFC score:12

  • Average scores from four 9HPT trials (two per hand, which are averaged for each hand and converted to reciprocals that are averaged)
  • Average scores of two T25FW trials
  • PASAT-3 number correct

Not only does change in the MSFC score correlate with change in the Expanded Disability Status Scale (EDSS), but it has been shown to be predictive of subsequent change in EDSS, suggesting increased sensitivity.11

Download MSFC

Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI) is an important tool not only in the diagnosis of MS but also in the monitoring of disease progression and treatment efficacy. MRI findings are often used as outcome measures for efficacy-focused clinical trials focusing on changes in the presence and appearance of T1 hypointense and T2 hyperintense lesions to assess optimal treatment response.13

Different MRI scan types may be used for assessments, including:14

  • T-1 weighted without gadolinium contrast agent to show hypointensities potentially indicative of permanent nerve damage
  • T-1 weighted with gadolinium to show enhancing lesions indicative of active inflammation
  • T-2 weighted to show total count of both existing and new lesions
  • FLAIR (fluid attenuated inversion recovery) to reduce spinal fluid interference and show MS activity
  • Spinal cord imaging to identify pathology

References

  1. Goldenberg MM. Multiple Sclerosis Review. PT. 2012;37(3):175-184.
  2. Duffy SS, Lees JG, Moalem-Taylor G. The contribution of immune and glial cell types in experimental autoimmune encephalomyelitis and multiple sclerosis. Mult Scler Int. 2014;1-17.
  3. Hart FM, Bainbridge J. Current and emerging treatment of multiple sclerosis. AJMC. 2016:1-11.
  4. Fernandez O. Is there a change of paradigm towards more effective treatment early in the course of apparent high-risk MS? Mult Scler Relat Disord. 2017;17:75-83.
  5. MS Symptoms. National Multiple Sclerosis Society. http://nationalmssociety.org/symptoms-diagnosis/ms-symptoms. Accessed May 28, 2020.
  6. Multiple Sclerosis. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269. Published April 19, 2019. Accessed May 14, 2020.
  7. RRMS – NMS. https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Relapsing-remitting-MS. Accessed May 14, 2020.
  8. Olsson T, Barcellos L, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017;13:25-36.
  9. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444-1452.
  10. Vickrey BG, Hays RD, Harooni R, et al. A health-related quality of life measure for multiple sclerosis. Qual Life Res. 1995;4:187-206.
  11. Cutter GR, Baier ML, Rudick RA, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain. 1999;122:871-882.
  12. NMSS_MSFC. https://www.nationalmssociety.org/nationalmssociety/media/msnationalfiles/brochures/10-2-3-31-msfc_manual_and_forms.pdf. Accessed November 16, 2020.
  13. Kaunzner UW, Gauthier SA. MRI in the assessment and monitoring of multiple sclerosis: an update on best practice. Ther Adv Neurol Disord. 2017;10(6):247-261.
  14. NMSS_MRI. https://www.nationalmssociety.org/Symptoms-Diagnosis/Diagnosing-Tools/MRI. Accessed May 14, 2020.