MS Overview

Multiple sclerosis impacts the central nervous system in several ways1,2

In multiple sclerosis (MS), accumulation of the damage in the central nervous system (CNS) overtakes the brain’s limited capacity to repair itself. This can eventually lead to decreased efficiency and altered connectivity between regions of the brain.1,2








Damage

Damage from MS can affect the whole CNS. MS is an autoimmune disease that can cause damage to several parts of the CNS, including white matter, grey matter, neurons, axons, and blood vessels. This damage can begin early in the disease.1,2





Lesions

Peripheral immune cells are present in MS lesions. Inflammation is more pronounced in the acute stages of MS but can continue into later stages of the disease as well. Lesions are a common occurrence in MS and are caused by immune cells crossing the blood–brain barrier into the brain where they take part in an inappropriate immune response against the CNS.3*





Remodeling

Remodeling can occur in MS but may have limited effectiveness. Remodeling in the CNS may partially restore or retain function and has multiple potential mechanisms.1,2,4





Connectivity

Connectivity in neural networks can be affected by MS. In MS, lesions can affect either the function of a brain region or communication between brain regions and networks. Changes in connectivity and network organization can occur in MS.5





Signaling

Signaling can be altered in the CNS in MS. The signaling of various molecules can be affected in MS.3,9




The clinical course of MS is heterogeneous2,3

There are a variety of disease courses in MS. These include clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). Patients can also experience radiologically isolated syndrome prior to their MS diagnosis.2,3

RRMS affects approximately 85% of patients with MS and is characterized by recurring relapses. Of those with RRMS, 80% will eventually progress to SPMS. PPMS affects approximately 10% to 15% of newly diagnosed patients with MS.2,3

Relapses (or exacerbations) are caused by inflammation in the CNS.2,19 Relapse intensity can vary from mild to severe, and the symptoms they cause can vary from patient to patient. They can last from a few days, to weeks, or even months.19

  • There are a variety of disease courses in MS. These include clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). Patients can also experience radiologically isolated syndrome prior to their MS diagnosis.2,3

  • RRMS affects approximately 85% of patients with MS and is characterized by recurring relapses. Of those with RRMS, 80% will eventually progress to SPMS. PPMS affects approximately 10% to 15% of newly diagnosed patients with MS.2,3

  • Relapses (or exacerbations) are caused by inflammation in the CNS.2,19 Relapse intensity can vary from mild to severe, and the symptoms they cause can vary from patient to patient. They can last from a few days, to weeks, or even months.19






Like the disease itself, the symptoms of MS
are heterogeneous and unpredictable3

MS can be challenging to manage due to the variability in symptoms between patients. Though each person living with MS can experience the disease in different ways, some of the most common symptoms of MS include20,21:
  • Fatigue
  • Numbness/
    tingling
  • Weakness
  • Dizziness and vertigo
  • Sexual problems
  • Emotional changes
  • Difficulty walking/gait issues
  • Vision problems
  • Bladder/bowel problems
  • Cognitive changes


Of these, fatigue is one of the most prevalent. In a large study of MS patients
(N = 25,728), about 81% experienced fatigue within their first year of diagnosis.

This high prevalence is consistent with other studies of MS fatigue.22,23






MS Fatigue Overview

Like MS itself, MS fatigue has
a variety of potential mechanisms24,25


There are a number of factors that are thought to contribute to your patients’ experience of MS fatigue.






MS FATIGUE AND YOUR PATIENTS

MS fatigue can affect many aspects of life24,32


Like other MS symptoms, MS fatigue can negatively affect patients’ lives.24,32



MS fatigue has been associated with24,32:

Difficulties in
physical
functioning

Difficulties in
cognitive
functioning

Reduced ability
to complete activities of daily living (ADLs)

Reduced ability
to work

Anxiety and
depression

Difficulties with
relationships and social integration



MS fatigue is unique to people living with MS and different than other types
of fatigue. If patients experience MS fatigue, it doesn’t mean they aren’t
trying to push through it.24,31,33

Compared with normal fatigue, MS fatigue can24,31:
  • Occur on a daily basis
  • Come on suddenly and more severely
  • Be aggravated by heat and humidity
  • Interfere with physical function
  • Interfere with cognitive function


MS fatigue can also impact care partners of patients living with MS.

In a study evaluating the effects of MS on care partners, nearly half of care
partners (n = 654 of 1,333) rated fatigue as the most stressful MS symptom.34



MS fatigue can worsen over time22

MS fatigue is highly prevalent, can occur early in the disease
course, and may worsen over time.22,23







In your patients who experience MS fatigue, do you find that this symptom
becomes more frequent or severe over time?

Symptomatic treatments for MS fatigue have limitations24,35-37

Pharmacologic agents:


  • Amantadine, modafinil, and methylphenidate, among others, can be used to treat symptoms of MS fatigue

  • In a recent randomized, double-blind study, these agents failed to show superiority vs placebo in improving MS fatigue and had more frequent adverse events*


 
Nonpharmacologic options:


  • Exercise

  • Simplifying work-related tasks

  • Cognitive behavioral therapies

  • Acupuncture



*As measured using validated fatigue outcomes measures including the Modified Fatigue Impact Scale (MFIS), Quality of Life in Neurological Disorders (Neuro-QoL), and Epworth Sleepiness Scale (ESS) in this randomized, placebo-controlled, 4-sequence, 4-period, crossover, double-blind study of patients with MS who reported MS fatigue (N = 141). Study participants received oral amantadine, modafinil, methylphenidate, or placebo. Each treatment period lasted for up to 6 weeks.37


Since MS and MS fatigue can affect every patient differently, symptomatic treatments may not work for everyone.24,35,36







How real patients experience MS fatigue


Quotes were collected from real MS patients.



How does MS fatigue impact your patients?






TALK TO YOUR Patients

When to bring up MS fatigue

An often "hidden" symptom, MS fatigue has been
associated with a variety of negative effects on patients.24,32,38
Patients may or may not bring it up with you proactively.

The resources below can help you recognize MS fatigue
in your patients and encourage them to speak with
you about it.






MS fatigue flashcard

A brief resource on how patients
experience MS fatigue and the impact it can have on their lives.


Download Now


Patient brochure

This resource can help inform your
discussions with patients and educate them on MS fatigue.


Download Now

  • MS fatigue flashcard

    A brief resource on how patients
    experience MS fatigue and the impact
    it can have on their lives.


    Download Now


  • Patient brochure

    This resource can help inform your
    discussions with patients and educate
    them on MS fatigue.


    Download Now


Ask your patients living with MS directly about their fatigue
to help you understand how it’s affecting them.



Additional resources about MS fatigue



Clinical papers on fatigue

Read more research about
MS fatigue from your peers.




MS product theaters

A 2-part, multi-chapter, virtual presentation series providing professional and patient perspectives on MS and MS fatigue.







Sign up for more information

To receive updates about MS fatigue, please sign
up by entering your information below.


The information you provide will only be used by Janssen Pharmaceuticals, Inc., our affiliates, and our service providers to provide you information about Janssen products, services, and programs relating to multiple sclerosis, and any optional requests indicated below. You may ask to stop receiving these communications by selecting UNSUBSCRIBE in the emails you receive. Our Privacy Policy further governs the use of the information you provide. By providing your information and selecting the SUBMIT button, you indicate that you read, understand, and agree to these terms.

*Indicates required field.






References: 1. Cerqueira JJ, Compston DAS, Geraldes R, et al. Time matters in multiple sclerosis: can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis? J Neurol Neurosurg Psychiatry. 2018;89(8):844-850. doi:10.1136/jnnp-2017-317509. 2. Filippi M, Bar-Or A, Piehl F, et al. Multiple sclerosis. Nat Rev Dis Primers. 2018;4(1):43. doi:10.1038/s41572-018-0041-4. 3. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545-558. doi:10.1038/nri3871.
4. Kerschensteiner M, Bareyre FM, Buddeberg BS, et al. Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis. J Exp Med. 2004;200(8):1027-1038. doi:10.1084/jem.20040452. 5. Tahedl M, Levine SM, Greenlee MW, Weissert R, Schwarzbach JV. Functional connectivity in multiple sclerosis: recent findings and future directions. Front Neurol. 2018;9:828. doi:10.3389/fneur.2018.00828. 6. Fleischer V, Koirala N, Droby A, et al. Longitudinal cortical network reorganization in early relapsing–remitting multiple sclerosis. Ther Adv Neurol Disord. 2019;12:1756286419838673. doi:10.1177/1756286419838673. 7. Shu N, Liu Y, Li K, et al. Diffusion tensor tractography reveals disrupted topological efficiency in white matter structural networks in multiple sclerosis. Cereb Cortex. 2011;21(11):2565-2577. doi:10.1093/cercor/bhr039. 8. Li Y, Jewells V, Kim M, et al. Diffusion tensor imaging based network analysis detects alterations of neuroconnectivity in patients with clinically early relapsing-remitting multiple sclerosis. Hum Brain Mapp. 2013;34(12):3376-3391. doi:10.1002/hbm.22158. 9. Mandolesi G, Gentile A, Musella A, et al. Synaptopathy connects inflammation and neurodegeneration in multiple sclerosis. Nat Rev Neurol. 2015;11(12):711-724. doi:10.1038/nrneurol.2015.222. 10. Chaudhry BZ, Cohen JA, Conway DS. Sphingosine 1-phosphate receptor modulators for the treatment of multiple sclerosis. Neurotherapeutics. 2017;14(4):859-873. doi:10.1007/s13311-017-0565-4. 11. Fischer I, Alliod C, Martinier N, Newcombe J, Brana C, Pouly S. Sphingosine kinase 1 and sphingosine 1-phosphate receptor 3 are functionally upregulated on astrocytes under pro-inflammatory conditions. PLoS One. 2011;6(8):e23905. doi:10.1371/journal.pone.0023905. 12. Van Doorn R, Van Horssen J, Verzijl D, et al. Sphingosine 1-phosphate receptor 1 and 3 are upregulated in multiple sclerosis lesions. Glia. 2010;58(12):1465-1476. doi:10.1002/glia.21021. 13. Fincher J, Whiteneck C, Birgbauer E. GPCR cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by LPA and S1P. Dev Neurosci. 2014;36(6):443-453. doi:10.1159/000364858. 14. Jaillard C, Harrison S, Stankoff B, et al. Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci. 2005;25(6):1459-1469. doi:10.1523/JNEUROSCI.4645-04.2005. 15. Postma FR, Jalink K, Hengeveld T, Moolenaar WH. Sphingosine-1-phosphate rapidly induces Rho-dependent neurite retraction: action through a specific cell surface receptor. EMBO J. 1996;15(10):2388-2392. 16. Meacci E, Garcia-Gil M. S1P/S1P receptor signaling in neuromuscular disorders. Int J Mol Sci. 2019;20(24):6364. doi:10.3390/ijms20246364. 17. Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci. 2004;5(2):146-156. doi:10.1038/nrn1326. 18. Garris CS, Blaho VA, Hla T, Han MH. Sphingosine-1-phosphate receptor 1 signalling in T cells: trafficking and beyond. Immunology. 2014;142(3):347-353. doi:10.1111/imm.12272. 19. Managing relapses. National Multiple Sclerosis Society. Accessed June 29, 2020. https://www.nationalmssociety.org/Treating-MS/Managing-Relapses. 20. MS symptoms. National Multiple Sclerosis Society. Accessed June 29, 2020. https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms. 21. Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016;9(Suppl 1):S5-S48. doi:10.1016/j.msard.2016.07.003. 22. Kister I, Bacon TE, Chamot E, et al. Natural history of multiple sclerosis symptoms. Int J MS Care. 2013;15(3):146-158. doi:10.7224/1537-2073.2012-053. 23. Kobelt G, Thompson A, Berg J, Gannedahl M, Eriksson J, MSCOI Study Group; European Multiple Sclerosis Platform. New insights into the burden and costs of multiple sclerosis in Europe. Mult Scler. 2017;23(8):1123-1136. doi:10.1177/1352458517694432. 24. Khan F, Amatya B, Galea M. Management of fatigue in persons with multiple sclerosis. Front Neurol. 2014;5:177. doi:10.3389/fneur.2014.00177. 25. Manjaly ZM, Harrison NA, Critchley HD, et al. Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(6):642-651. doi:10.1136/jnnp-2018-320050. 26. Bisecco A, Di Nardo F, Docimo R, et al. Fatigue in multiple sclerosis: the contribution of resting-state functional connectivity reorganization. Mult Scler. 2018;24(13):1696-1705. doi:10.1177/1352458517730932.
27. Finke C, Schlichting J, Papazoglou S, et al. Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue. Mult Scler. 2015;21(7):925-934. doi:10.1177/1352458514555784. 28. Tartaglia MC, Narayanan S, Arnold DL. Mental fatigue alters the pattern and increases the volume of cerebral activation required for a motor task in multiple sclerosis patients with fatigue. Euro J Neurol. 2008;15(4):413-419. doi:10.1111/j.1468-1331.2008.02090.x. 29. Engström M, Flensner G, Landtblom AM, Ek AC, Karlsson T. Thalamo-striato-cortical determinants to fatigue in multiple sclerosis. Brain Behav. 2013;3(6):715-728. doi:10.1002/brb3.181. 30. Chen MH, Wylie GR, Sandroff BM, Dacosta-Aguayo R, DeLuca J, Genova HM. Neural mechanisms underlying state mental fatigue in multiple sclerosis: a pilot study. J Neurol. Published online April 29, 2020. doi:10.1007/s00415-020-09853-w. 31. Fatigue. National Multiple Sclerosis Society. Accessed June 29, 2020. https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Fatigue. 32. Lerdal A, Gulowsen Celius E, Krupp L, Dahl AA. A prospective study of patterns of fatigue in multiple sclerosis. Eur J Neurol. 2007;14(12):1338-1343. doi:10.1111/j.1468-1331.2007.01974.x. 33. Cook KF, Bamer AM, Roddey TS, Kraft GH, Kim J, Amtmann D. Multiple sclerosis and fatigue: understanding the patient's needs. Phys Med Rehabil Clin N Am. 2013;24(4):653-661. doi:10.1016/j.pmr.2013.06.006. 34. McKenzie T, Quig ME, Tyry T, et al. Care partners and multiple sclerosis: differential effect on men and women. Int J MS Care. 2015;17(6):253-260. doi:10.7224/1537-2073.2014-083. 35. Ayache SS, Chalah MA. Fatigue in multiple sclerosis—insights into evaluation and management. Neurophysiol Clin. 2017;47(2):139-171. doi:10.1016/j.neucli.2017.02.004. 36. Hadjimichael O, Vollmer T, Oleen-Burkey M. Fatigue characteristics in multiple sclerosis: the North American Research Committee on Multiple Sclerosis (NARCOMS) survey. Health Qual Life Outcomes. 2008;6(10):1-11. doi:10.1186/1477-7525-6-100. 37. Nourbakhsh B, Revirajan N, Morris B, et al. Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial. Lancet. 2020:1-11. doi:10.1016/S1474-4422(20)30354-9. 38. Penner IK. Evaluation of cognition and fatigue in multiple sclerosis: daily practice and future directions. Acta Neurol Scand. 2016;134(Suppl 200):19-23. doi:10.1111/ane.12651

If you are a US healthcare professional,
please click the following button:




If you are a person living with MS or a care partner,
please click the following button:

I AM LIVING WITH MS
OR A care partner

Inflammation is more pronounced in the acute stages of MS but can continue into later stages of the disease as well. Early lesions show invading peripheral immune cells, which can include macrophages, T cells, B cells, and plasma cells. At later stages of the disease, these cells, along with activated CNS-resident microglia and astrocytes, promote gray and white matter damage.3

*A network of vessels and tissue that restricts entry of certain substances into the brain.

Reestablishing or rearranging neural connections.

Cell type that creates myelin in the CNS.

§Specialized end of an axon that determines and guides the direction of growth.

In a 1-year longitudinal study, patients with early RRMS meeting criteria for no evidence of disease activity (NEDA-3; n = 56) and those with evidence of disease activity (n = 36) showed increases in local cortical connections. This change was not observed in healthy controls (n = 101) over the same period.6

Thank you
for signing up!
Thank you
for signing up!