Neurological Symptoms in primary care Part 3: Tiredness

Even though in most cases, neurological symptoms are not a cause for alarm, lack of knowledge can lead to failure to recognise conditions that may require rapid referral and treatment. In this series we look at commonly presenting signs and symptoms, explore their possible causes and flag up those that need urgent attention

Tiredness (or using the slightly more medical-sounding word ‘fatigue’) is rather difficult to define, but most people will understand you when you use the word. A reasonable definition would include a lack of, or decreased, energy and physical or mental exhaustion.¹ The experience and perception of tiredness is subjective: some people are more tolerant than others.

Tiredness is also common. A postal survey of patients found that nearly 20% of people had been tired for a month or more,² but it must be added that self-reported tiredness may overestimate the true incidence. Each year 1.5% of people see their GP because of tiredness, and tiredness is the primary complaint in 5–7% of GP consultations.^3,4 After respiratory problems, fatigue is the most common symptom complained of in primary care.⁵ Patients will report only about one in 400 episodes of fatigue to their GP.⁶ A GP with a list size of 2,000 can expect 26 presentations a year for fatigue as the main symptom, and 150 more that have fatigue as well as other symptoms.⁵

CAUSES OF TIREDNESS

Tiredness has physical, psychological and social dimensions. A distinction can usefully be made between lack of energy, lack of motivation, and sleepiness – all of these can be described as ‘tiredness’, but will suggest different diagnoses.

The differential diagnosis of fatigue is huge. Indeed fatigue is probably a feature of all illness with the possible exception of mania. In about three quarters of cases, the cause of the fatigue turns out to be psychosocial, and in about a tenth a physical cause is found.⁷ Some of the rest will be diagnosed as having Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Around half of patients who present with tiredness think that their problem is psychological.⁸

Tiredness due to non-physical causes is more common in women and in those with a past history of either fatigue or depression. An episode of tiredness may be provoked by a physical stress such as an infection (especially with the Epstein-Barr virus, the one responsible for glandular fever), a psychological stress such as bereavement, or a social stress such as a relationship problem. Once begun, other factors may keep the tiredness going, such as physical inactivity, ongoing stresses, and sleep abnormalities.⁹ In particular, physical activity can be seen as a vicious circle: a reduction in exercise results in reduced muscle fitness which then, when exercised, results in exaggerated tiredness.

Tiredness is more common in lower socio-economic groups (who are more likely to have symptoms but less likely to be recognised as having fatigue).¹ Women who have children aged less than 6 years are at particular risk: this is not surprising as young women with families work an average 77 hours a week.⁶

Of patients seen in primary care who have had tiredness for more than 6 months, around a third will fit the diagnostic criteria for CFS/ME.⁸ CFS/ME is a major cause of illness and disability,¹⁰ but all patients with chronic tiredness have significant resulting disability.⁸

USEFUL THINGS TO ASK

As ever, it is important not to miss a serious cause for the tiredness. Serious disease may be rare, but the consequences of a missed diagnosis are significant. The possible causes of tiredness are myriad, so there is a need to explore several avenues as a matter of routine when a patient consults.

Having discovered the nature and effects of the tiredness, ask about:4

• Bleeding (gastrointestinal [GI] tract, e.g. rectal blood loss or melaena; menorrhagia)
• GI symptoms such as dyspepsia, heartburn (may result in internal bleeding)
• Urinary symptoms including polyuria and polydipsia (may be diabetes)
• Quality and length of sleep and specifically about sleep apnoea (episodic night time breathlessness, daytime sleepiness and often snoring)
• Recent infections: almost any viral infection can result in a spell of fatigue
• Joint pain or swelling: being in pain causes tiredness, and inflammatory arthritis can cause systemic disturbance
• Mental health problems including concentration, motivation, stressful events and mood – depression and anxiety are associated with tiredness. Ask about other symptoms associated with depression; sleep disturbance, guilt, lack of pleasure in doing things. Two affirmative answers to the following questions has 97% sensitivity when screening for depression:¹¹
  • ’During the past month have you often been bothered by feeling down, depressed or hopeless?’
  • ‘During the past month have you often been bothered by little interest or pleasure in doing things?’

Ask also about sources of stress: this may not be too helpful as most people feel they have got stresses of some sort most of the time, but identifying a particular stress can be a good way of convincing a patient that there is indeed a logical reason for how they feel.

• Review medications, not forgetting over the counter drugs. Some drugs can cause tiredness. A patient may be taking a lot of antacid tablets, suggesting dyspepsia even if symptoms are not volunteered.
• Review alcohol intake (specifically over-use)

RED FLAGS FOR TIREDNESS

There are things that may emerge from questioning that will set alarm bells ringing. Not only is there a serious possible cause for the tiredness, but the possibility should be explored without delay: a hospital referral is likely to be needed. Of particular significance are:⁴

• Weight loss – more than 5% of body weight lost unintentionally over 6-12 months
• Any features of malignancy, including haemoptysis, dysphagia, rectal bleeding, breast lump, post-menopausal bleeding.
• Lymphadenopathy (including lymph nodes more than 2cm across, those that are not tender, those that feel hard, those that are increasing in size or those in the axillae or above the collar bone).
• Features of cardio-respiratory disease including sleep apnoea.
• Features of inflammatory arthritis, vasculitis or connective tissue disorders (particularly joint swelling).
• Focal neurological signs.

WILL A BLOOD TEST HELP?

Only half of people who consult because of tiredness end up having any investigations or blood tests.⁴ As long as there are no worrisome features, 75% of those with tiredness who see their GP never come for a subsequent appointment: either they are satisfied with the explanation they have been given, or have got better (or preferably both).

In the rather ghoulishly named VAMPIRE Trial (VAgue Medical Problems In REsearch),12 four basic blood tests were used – haemoglobin (Hb), thyroid stimulating hormone (TSH), erythrocyte sedimentation rate (ESR), and glucose – which only showed an abnormality in only 8% of instances, meaning that 92% of patients did not benefit from having their blood tested except as a confirmation of the absence of a serious disease. However, NICE Clinical Knowledge Summaries recommend these four basic blood tests, plus tests of kidney and liver function and a test for coeliac disease.¹

WHAT IS GOING TO HAPPEN NOW?

A study from general practice of patients presenting with tiredness found that about half had improved after 6 months.⁵ A poorer outlook was associated with:

• Being female
• Symptoms present for more than 3 months
• A history of emotional illness.

Only 2% of patients presenting to GPs with fatigue are referred to a secondary care specialist.⁵

COULD IT BE CFS/ME?

The typical patient with CFS/ME is an active intelligent young woman who is reduced to a ‘shadow of her former self’. Because CFS/ME can be so disabling, because it affects people in the prime of life, and because there is no reliable cure, the disease and its sufferers repeatedly hit the headlines.

However, many medical authorities dispute that CFS/ME as defined is a useful diagnosis,^13–15 even though its status as a medical entity is the subject of a working group report to the Chief Medical Officer of 2001.16 To those who experience CFS/ME, the denial that the condition even exists can seem like professional negligence if not misogyny.

CFS/ME has had a lot of different names including neuraesthenia, Royal Free disease, yuppie flu and myalgic encephalomyelitis (ME). Some descriptions of the illness are quite old, dating back to 1781.17 Diagnostic criteria were only formulated in 1978,¹⁷ and the current consensus was only agreed in 1991,¹⁸ making old sources unreliable and estimates of prevalence open to dispute.

Myalgic encephalomyelitis is the most popular name with patients. ME is also the term favoured by most of the relevant self-help organisations, even though there is no evidence that encephalitis plays any part in the symptoms.¹⁹ The medical establishment currently favours the term Chronic Fatigue Syndrome.¹⁸

NICE says that CFS/ME affects 0.2% – 0.4% of the population, but admits that good epidemiological evidence is lacking.²⁰ A community survey of adults in South East England found that 0.2% of respondents considered themselves to have ME, but 1% reported some of the diagnostic features.² The ME Association says that 250,000 people in Britain have ME.²¹

CFS/ME is found in all social classes and ethnic groups. The only known demographic risk factor is that CFS/ME is more common in women.²²

Nobody knows what causes CFS/ME. It may not even be a single condition, but a group of symptoms that can result from a number of different, or combinations, of causes. A mass of research data exists, the results of which have suggested different possible causative mechanisms. However, little of the research is beyond criticism, and the authoritative consensus remains that the cause(s) of CFS/ME is unknown.¹⁸ Accordingly there are no blood or other tests which will reliably confirm a diagnosis of CFS/ME. Similarly, there are no completely reliable physical signs.

There is good evidence that infection with the Epstein-Barr virus, viral hepatitis and meningitis can trigger CFS/ME.²³ After a bout of glandular fever, up to 10% of patients develop CFS/ME-like symptoms.²⁴ Chronic consequences from other viral triggers are less likely, and tend to be more common in patients who had symptoms of fatigue before they contracted the virus: some people seem predisposed to CFS/ME which is then triggered by a viral infection.

Stress and adverse life events certainly make an individual more likely to develop CFS/ME after a viral trigger.²³ Three fifths of individuals with CFS/ME have no previous psychiatric diagnoses, but the illness itself can cause significant stress and sometimes leads to depression.²⁴ The minority of patients who are referred to specialist clinics for tiredness are a selected group who are likely to have more severe symptoms: they tend to be perfectionist and over-achieving,23 but this is probably not true of the generality of less severe CFS/ME seen in primary care. Research carried out on referred populations can be misleading.

Diagnosing CFS/ME

As far as a patient with CFS/ME is concerned, making the diagnosis is seen as the most helpful thing which a healthcare professional can do.²⁵ This requires having positive diagnostic criteria, and at the same time having sufficient regard to the differential diagnosis to be able to exclude other problems.

The diagnosis of CFS/ME is based primarily on the history, and the clinician being prepared to accept that the diagnosis is possible. A clinical examination, though recommended, is not usually helpful.²⁶ A few investigations designed to exclude other diagnoses can be useful, with the proviso that a diagnosis by exclusion is rarely satisfying to a patient, and the delay in getting the results back can cause anxiety. And, of course, if enough tests are done, eventually one will show an abnormality either by chance or because every blood test result has a margin for error.²⁷

Prognosis of CFS/ME

The chance of getting over CFS/ME is related to how bad it is. Work on CFS tends to be derived from the experience of specialised clinics where presumably the more severe cases are referred. These suggest that up to 50% of adults but up to 94% of children with CFS/ME improve over 6-year follow-up. Only 6% of patients with CFS/ME return to completely normal functioning.

Participation in a self-help group is associated with a worse prognosis for the CFS/ME,23 but this may be no more than a reflection of the type of people who join self-help groups, and perhaps suggests that the more severely affected and those making little progress are more likely to become involved. In addition, some organisations offer very specific cures for CFS/ME,28 notions that would not be supported by the majority of expert medical opinion.

CONCLUSION

Feeling tired means there is a reduction in physical and mental enthusiasm, and this is not the way most people would choose to live their lives. When you include their unique experiences and stresses as possible causes of tiredness, there are as many diagnostic possibilities as there are patients in the practice. An holistic approach is required, and the remote possibility of serious illness must be constantly in mind.

CFS/ME has a special status as a cause of tiredness, and generates high emotion is some people. It is indeed an unpleasant condition, and since so far the results of treatment are disappointing, many different people have their own ideas about what should be done. This situation of uncertainty about cause and treatment is not new to medicine and provokes frustration for patients and healthcare professional alike: consider from history the theories and proposed treatments prevailing for tuberculosis before the tubercle bacillus was found to be the culprit. A parallel ‘breakthrough’ for CFS/ME appears to be as far away as ever.

REFERENCES

1. NICE CKS Tiredness/fatigue in adults. https://cks.nice.org.uk/tirednessfatigue-in-adults

2. Pawlikowska T, Chalder T, Hirsch S R et al. Population based study of fatigue and psychological distress. BMJ 1994;308:763-6.

3. Gallagher, A.M., Thomas, J.M., Hamilton, W.T. and White, P.D. (2004) Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001. Journal of the Royal Society of Medicine 97(12), 571-575.

4. Hamilton, W., Watson, J. and Round, A. Investigating fatigue in primary care. BMJ 2010,341,c4259.

5. Ridsdale L, Evans A, Jerrett W et al. Patients with fatigue in general practice: a prospective study. BMJ 1993;307:103-6.

6. Ridsdale L, Evans A, Jerrett W et al. Patients who consult with tiredness: frequency of consultation, perceived causes of tiredness and its association with psychological distress. Br J Gen Pract 1994;44:413-416.

7. Gambrill E C and Mead M. ‘Tired all the time’ Update 1994;49:233-235.

8. Darbishire L, Ridsdale L and Seed P T. Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care. Br J Gen Pract 2003;53:441-5.

9. Sharpe M and Wilks D. ABC of psychological medicine. Fatigue. BMJ 2002;325:480-3.

10. Ridsdale L. Tired all the time. BMJ 1991;303:1490-1.

11. Moncreiff G & Fletcher J. 10-minute consultation. Tiredness. BMJ 2007;334:1221.

12. Koch, H., van Bokhoven, M.A., ter Riet, G. et al. (2009) Ordering blood tests for patients with unexplained fatigue in general practice: what does it yield? Results of the VAMPIRE trial. Br J Gen Pract 59(561), e93-e100.

13. Fitzpatrick M. Myalgic encephalomyelitis - the dangers of Cartesian fundamentalism. Br J Gen Pract 2002;52:432-3.

14. Stanley I, Salmon P, and Peters R. Doctors and social epidemics: the problem of persistent unexplained physical symptoms, including chronic fatigue. Br J Gen Pract 2002;52:355-6.

15. Strauss S E. Caring for patients with chronic fatigue syndrome. BMJ 2002;324:124-5.

16. CFS/ME. Working Group. Report to the Chief Medical Officer of an independent working group. London:Department of Health,2001.

17. Archer M I. The post-viral syndrome: a review. J Roy Coll Gen Pract 1987;37:212-214.

18. Straus S E. Chronic fatigue syndrome. BMJ 1996;313:831-2.

19. Thomas P K. The chronic fatigue syndrome: what do we know? BMJ 1993;306:1557-8.

20. Baker R & Shaw EJ. Diagnosis and management of chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ 2007;335:446-8

21. ME Association. http://www.meassociation.org.uk/me-association/

22. Reid S, Chalder T, Cleare A et al for “Clinical Evidence” Chronic fatigue syndrome. BMJ 2000;320:292-6.

23. Cleare A J and Wessely S C. Chronic fatigue syndrome: an update. Update 1996;53:61-69.

24. Pinching A J. Chronic fatigue syndrome. Prescribers’ Journal 2000;40(2):99-106.

25. Elliott H. Use of formal and informal care among people with prolonged fatigue: a review of the literature. Br J Gen Pract 1999;49:131-134.

26. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy). NICE clinical guideline 53. August 2007 http://www.nice.org.uk/nicemedia/live/11824/36190/36190.pdf

27. BMJ Editor’s choice: Are you normal? BMJ 1997;314:0

28. Autoimmunity Research Foundation. http://autoimmunityresearch.org/