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Fatigue: an overview of causes and management

Helen Rowlands, Community Specialist Occupational Therapist
Fran Jackson, MS Specialist Nurse
Stockport

Way Ahead 2009;13(4):10-11

Fatigue is one of the most common symptoms experienced by people with MS. Understanding the causes of fatigue is key to identifying the most effective management strategies. In the following article, Helen Rowlands and Fran Jackson explore the complex nature of this symptom, and emphasise the importance of a multidisciplinary approach to its management.

Fatigue: 'A subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual and desired activities'1.

Introduction

The following overview highlights some of the primary and secondary causes of fatigue in MS, acknowledging that it is a common symptom in a wide range of neurological and nonneurological conditions2, 3. It demonstrates that a multidisciplinary but individualised assessment is pivotal to the success of the fatigue management strategies presented.

Research suggests that between 65-97% of people with MS experience significant fatigue4 and it is a presenting symptom in one third of people with MS5. 15-40% of people with MS describe fatigue as their most disabling symptom6. Research has also linked fatigue with symptoms of depression and identified it as one of the most common reasons for unemployment amongst the MS population.

But while it is important to recognise the proportion of people with MS affected by fatigue, and to assess the extent of its impact, it is also important to understand that there may be different physiological mechanisms behind the presentation of fatigue.

Presentation of fatigue in MS

Fatigue in MS is a complex symptom that can present in the form of three different clinical entities7:

  • Asthenia or lassitude which is present at rest and described as an overwhelming feeling of tiredness. This has an adverse effect on both physical and mental activity6, 8-11. This type of fatigue is linked to the body's immune response7.
  • Fatigability or acute fatigue is localised to specific muscle groups and occurs during or after exercise or activity. This type of fatigue is related to activity within the pyramidal tracts (see figure 1).
  • Worsening of symptoms may be a consequence of fatigue and can induce symptoms such as blurred vision, reduced balance or slurred speech.

Causes of fatigue

Understanding the physiological processes that are responsible for the onset of fatigue, can help identify some of the causes of MS related fatigue, which are often complex and interdependent. The causes of fatigue are broadly categorised as either primary or secondary1.

Primary fatigue

Primary fatigue is directly related to the disease process6 and may be the result of inflammation, demyelination or axonal damage12.

  • Inflammation The inflammatory processes seen in MS may be related to a disrupted immune response. The immune system plays a substantial role in MS fatigue and it can be the first symptom of an impending relapse13. Higher levels of immune activity are often seen in MS fatigue and may be detected by testing for the presence of certain immune markers8, 9. This type of fatigue is not unique to MS and can present in other autoimmune conditions6, 8, 11.

    • It has been hypothesised that in people with MS related fatigue, immune activity may either be the trigger or the result of low glucose metabolism in areas of the brain involved in motor planning including the prefrontal cortex and basal ganglia5, 7, 10.

  • Demyelination Demyelination is the result of the inflammatory process that impairs the conduction of impulses. Nerve conduction in demyelinated nerves may be heat sensitive. This type of fatigue is peculiar to MS and is known as Uhthoff's phenomenon14. It manifests itself as a worsening of symptoms accompanied by fatigue in a hot environment.

    • Herndon suggested that the demyelinated membrane takes longer to recover due to a build up of sodium ions known as 'nerve fibre fatigue' or 'conduction block'15. Anecdotally, this might translate into the ability to walk a short distance without difficulty, but on continuing to walk developing a limp which further develops into partial paralysis. These symptoms would characteristically disappear after a short rest or recovery period. Recent studies also demonstrated an association between fatigue in MS and the reduction of membrane excitability after exercise in the motor cortex of the brain16. The suggestion that fatigue in MS involves a central pathology is further supported by the use of sophisticated MRI techniques which have demonstrated a correlation between the number of white matter lesions and grey matter atrophy and fatigue in MS17.

  • Axonal Damage Research studies have observed that where fatigue was experienced in the first two years since diagnosis, brain atrophy occurred over the following six years18. Widespread cerebral axonal damage has also been seen to correlate with MS related fatigue and adaptive neuroplasticity19. This may involve the altered cerebral activity that has been demonstrated by EEG studies where the person with MS related fatigue experienced increased activity in the brain before exercise and decreased cerebral inhibition of activity after exercise20. In layman's terms, such findings suggest that people with MS related fatigue have to use more brain power to participate in exercise than those with MS not experiencing fatigue.

Central fatigue

Central fatigue develops in the central nervous system. In MS it is associated with the selective involvement of the frontal cortex, white matter and basal ganglia, which may cause low motivation, low initiative and reduced concentration21, 22. The frequency with which physical and mental fatigue occur together is compelling evidence for some researchers that fatigue in MS is caused by central abnormalities6.

Central fatigue is not exclusive to MS and can be present in other central nervous system disorders (see figure 1).

A diagram of the different areas of brain activity

Figure 1. A diagram of the different areas of brain activity2

Secondary fatigue

Secondary fatigue refers to the causes of fatigue that are not directly due to MS. These secondary causes are many and varied. Figure 2 illustrates a number of potential causes of secondary fatigue.

A diagram illustrating potential contributory factors affecting MS fatigue

Figure 2. A diagram illustrating potential contributory factors affecting MS fatigue1

The array of potential influencing factors highlights the need for an individualised assessment, ideally within a multidisciplinary context. It is these factors that health professionals aim to identify and influence to enable people with MS to regain some control over their fatigue.

Managing fatigue

It is important that people experiencing MS-related fatigue recognise the central role they must play in identifying their own contributory factors. The MS Trust publication Living with fatigue23 offers ideas to help people identify and address these factors. Health professionals need to support people in identifying the causes and align any interventions with the aim of maximising energy and managing available energy more effectively.

Medication

A medication review is an essential part of assessment, as many of the medications used for symptom management and some co-morbid conditions (particularly cardiovascular) report fatigue as a significant side effect. Medications that may cause fatigue include: analgesics; anti-spasticity medication; anticonvulsants; anti-hypertensives; antidepressants; antihistamines; anti-inflammatories; HRT; and statins.

Exercise

For many years people with fatigue were advised to avoid exercise. But the theory underpinning that advice has since been turned on its head and physical de-conditioning has been shown to contribute to fatigue and general poor health in the MS population24. Research has demonstrated that aerobic and strength exercises can reduce motor fatigue in MS and that physical activity can significantly improve levels of fatigue25, 26. Ideally, people with MS related fatigue will be advised on an appropriate exercise regime by a physiotherapist, but they also need to take responsibility for their ongoing fitness themselves.

Prioritising, planning and pacing

Traditional advice for managing fatigue includes the 3 'P's approach of Prioritising, Planning and Pacing. We often use the analogy of comparing the amount of energy someone has to holding money in the bank. There are essential bills to be paid but any money remaining can be spent on enjoyable items. Similarly people with MS related fatigue need to use their available energy on essential tasks but save some for enjoyable activities.

Fatigue management programmes

Research into the efficacy of energy conservation programmes has pointed to the benefits such programmes offer people with MS fatigue27, 28. The delivery of such programmes can vary - a programme designed by the College of Occupational Therapists is delivered on a one to one basis29, whilst the MS Trust supported study into a fatigue management programme taking place at University Hospital Birmingham is delivered in a group format running over several weeks. While such programmes may not offer a 'one size suits all' solution to the management of fatigue in MS, they ought to be considered as part of every individualised assessment.

Conclusion

Fatigue is a complex symptom that affects people with MS in many different ways. Key to the effective management of this symptom is accurate understanding of the physiological mechanisms responsible for it, identification of factors which may be contributing to it, and the central involvement of the individual experiencing it.

References

  1. Multiple Sclerosis Council for Clinical Practice Guidelines.
    Fatigue and multiple sclerosis.
    Washington DC: Paralysed Veterans of America: 1998.
  2. Chaudhuri A, Behan PO.
    Fatigue in neurological disorders.
    Lancet 2004; 363(9413): 78-88.
  3. Smith C, Hale L.
    The unique nature of fatigue in multiple sclerosis: prevalence, pathophysiology, contributing factors and subjective experience.
    Phys Ther Rev 2007; 12(1): 43-51.
  4. Debouverie M, Pittion S, Guillemin F, et al.
    Fatigue scales used in multiple sclerosis.
    Rev Neurol 2002; 158(11): 1139-1143.
  5. Krupp LB.
    Fatigue in multiple sclerosis: definition, pathophysiology, and treatment.
    CNS Drugs 2003; 17(4): 225-234.
  6. Bakshi R.
    Fatigue associated with multiple sclerosis: diagnosis, impact and management.
    Mult Scler 2003; 9(3): 197-227.
  7. Iriarte J, Subira M, De Castro P.
    Modalities of fatigue in multiple sclerosis: correlation with clinical and biological factors.
    Mult Scler 2000; 6(2): 124-130.
  8. Flachenecker P, Bihler I, Weber F, et al.
    Cytokine mRNA expression in patients with multiple sclerosis and fatigue.
    Mult Scler 2004; 10(2): 165-169.
  9. Heesen C, Nawrath L, Reich C, et al.
    Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour? J Neurol Neurosurg Psych 2006; 77: 4-9.
  10. Krupp LB, La Rocca NG, Muir J, et al.
    Fatigue characteristics in systemic lupus erythmatosus.
    J Rheumatol 1990; 17:1450-1452.
  11. Roelcke U, Kappos L, Lechner-Scott J, et al.
    Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: A18 F-fluorodeoxyglucose positron emission tomography study.
    Neurology 1997; 48(6): 1566-1571.
  12. Kos D, Kerckhofs E, Nagels G, et al.
    Origin of fatigue in multiple sclerosis: Review of the literature.
    Neurorehab Neural Res 2008; 22(1): 91-100.
  13. Krupp L.
    Fatigue in multiple sclerosis.
    New York: Demos; 2004.
  14. Rasminsky M.
    The effects of temperature on conduction in demyelinated single nerve fibres.
    Arch Neurol 1972; 28(5): 287-292.
  15. Herndon R.
    Fatigue in multiple sclerosis.
    Int J of MS Care 1999; 1(1): 7-11.
  16. Liepert L, Mingers D, Heesen C, et al.
    Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study.
    Mult Scler 2005; 11(3): 316-321.
  17. Sepulcre J, Masdeu J, Goni J, et al.
    Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways.
    Mult Scler 2009; 15(3): 337-344.
  18. Marrie R, Fisher E, Miller D, et al.
    Association of fatigue and brain atrophy in multiple sclerosis.
    J Neurol Sci 2005; 228(2): 161-166.
  19. Tartaglia MC, Narayanan S, Francis SJ, et al.
    The relationship between diffuse axonal damage and fatigue in multiple sclerosis.
    Arch Neurol 2004; 61(2):201-207.
  20. Leocani L, Columbo B, Magnani G, et al.
    Fatigue in multiple sclerosis is associated with abnormal cortical activation to voluntary movement - EEG evidence.
    Neuroimage 2001; 13(6 pt 1):1186-1192.
  21. Leocani L, Colombo B, Comi G.
    Physiopathology of fatigue in multiple sclerosis.
    Neurological Scientist 2008; 29(Suppl 2): 241-243.
  22. Téllez N, Alonso J, Rio J, et al.
    The basal ganglia: a substrate for fatigue in multiple sclerosis.
    Neuroradiology 2008; 50(1): 17-23.
  23. Multiple Sclerosis Trust.
    Living with fatigue.
    Letchworth Garden City: MS Trust; 2006.
  24. Krupp LB, Alvarez LA, LaRocca NG, et al.
    Fatigue in multiple sclerosis.
    Arch Neurol 1988; 45(4): 35-37.
  25. McCullagh R, Fitzgerald AP, Murphy R.
    Long-term benefits of exercising on quality of life and fatigue in multiple sclerosis patients with mild disability: a pilot study.
    Clin Rehabil 2008; 22(3): 206-214.
  26. Fragoso YD, Santana DLB, Cruz Pinto R, et al.
    The positive effects of a physical activity program for multiple sclerosis patients with fatigue.
    NeuroRehabilitation 2008; 23(2):153-157.
  27. Mathiowetz VG, Finlayson ML, Matuska KM, et al.
    Randomized controlled trial of an energy conservation course for persons with multiple sclerosis.
    Mult Scler 2005; 11(5): 592-601.
  28. Navipour H, Madani H, Mohebbi MR, et al.
    Improved fatigue in individuals with multiple sclerosis after participating in a short-term self-care programme.
    NeuroRehabilitation 2006; 21(1): 37-41.
  29. Harrison S.
    Fatigue management for people with multiple sclerosis.
    2nd edition.
    London: College of Occupational Therapists; 2007.

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