Dr David Kernick discusses signs and methodology that can be used to determine whether headache is a manifestation of an underlying brain tumour
  • Although a brain tumour can be indicated by a number of signs or symptoms, headache presentation is invariably a cause for concern for both patient and doctor
  • The decision to investigate for tumour is based on a number of complex factors against a background of a limited evidence base
  • Although guidelines for investigation have been developed, the focus is on secondary care and support for GPs is limited
  • There are benefits to early diagnosis of brain tumour but the disadvantages in terms of the exposure of incidental pathology should not be overlooked.

The annual primary care consultation rate for headache is 4.4 per 100 patients, of whom 2% are referred to secondary care for further assessment.1 The presence of headache is invariably worrying for the patient and GP, as it features among a number of signs and symptoms of brain tumour. The annual incidence of this type of tumour is approximately 0.01%-0.06%, of which almost 77% will present in patients aged >50 years.2 Table 1 shows how the relative risk of developing a brain tumour increases with age (see Table 1).3

Table 1: Relative risk of tumour3
Age band (years) Relative risk of tumour against base rate at 18-29 years (2.6 tumours/year/100,000 population)
18-29 1.0
30-39 1.5
40-49 2.2
50-59 4.3
60-69 6.9
70-79 7.9
?80+ 5.9
Kernick D, Ahmed F, Bahra A et al. Imaging patients with suspected brain tumour. Guidance for primary care. Br J Gen Pract 2008; 58 (557): 880-885. Reproduced with permission.

Developing guidelines

Decision pathways based on rigorous studies should form the basis for guideline development. Unfortunately this is unlikely to be the case for a condition such as headache, as these studies require analysis of a large number of consecutive patients in relevant settings, with prospective randomised studies and blind interpretation of data. Currently, studies are limited by small sample sizes, which have a wide range of estimates. They are open to bias from retrospective recall, and there is a focus on specialist centres, where there is a lack of distinction between acute and chronic presentations. Although many studies have highlighted a relative lack of sensitivity of computed tomography (CT) compared with magnetic resonance imaging (MRI),4 both techniques have improved in sensitivity over time, rendering study comparison difficult.

‘Significant pathology’ is interpreted differently and the relevance of abnormal findings to clinical presentations is uncertain. In view of the difficulties with developing a rigorous evidence base, a professional consensus that combines evidence with clinical experience is needed.

Table 2 lists the key features of headache that should prompt investigation as recommended by current guidelines.

Table 2: Indications for investigation as recommended by different guidelines
Presentation SIGN5 EFNS6 NICE7 BASH3
(for general practice)
BASH8
(for suspected brain tumour)
US Headache Consortium9
New onset over the age of 50 years ? ? ? ? ?
Focal neurology ? ? ? ?
Non-focal neurology (e.g. cognitive impairment) ? ? ?
Change in headache characteristics—progressive (including atypical aura) ? ? ? ? ? ?
Change with posture ? ? ?
Headache that wakes up ? ? ?
Headache on awakening
Precipitated by physical exertion ?
Exacerbated by physical exertion ?
Precipitated by Valsalva ?
Exacerbated by Valsalva ? ?
Risk factors for cerebral venous thrombosis ?
New headache with human immunodeficiency virus ? ? ?
New headache with cancer elsewhere ? ? ? ?
Pulse synchronous tinnitus
Headache with nausea/vomiting ? ? ?
Headache with seizure history ?
SIGN=Scottish Intercollegiate Guidelines Network; EFNS=European Federation of Neurological Societies; NICE=National Institute for Health and Care Excellence; BASH=British Association for the Study of Headache

Headache at diagnosis

Headache will feature at least occasionally for approximately 70% of patients with a brain tumour.10 The frequency at the time of diagnosis is confounded by recollection bias and varies with clinical setting between 23% and 56%.10 There is only a 0.09% likelihood of a patient visiting their GP with headache that is a result of a brain tumour.10 If the GP is able to reach a diagnosis of a primary headache at presentation (as a result of migraine, tension-type, or cluster), the risk that it is caused by a tumour is reduced to 0.045%.11 Headache that presents as a symptom of tumour has no consistent clinical pattern and the lesion is not usually positioned at the focus of the headache pain.

The difficulty comes for the GP when patients complain of isolated headache, where there are no accompanying signs or clear diagnostic pattern; the estimated proportion of these patients ranges from 2% to 16%.12-14

Investigation

Factors that contribute to the GP’s decision whether or not to test for underlying pathology in the presence of headache include:

  • therapeutic value
  • clinical confidence
  • consultation time constraints
  • availability of imaging
  • the GP’s approach to risk and uncertainty
  • the degree of reassurance required for an anxious patient
  • medicolegal concerns.

The context in which the decision is made also plays an important part. In primary care, GPs experience difficulty in diagnosing headaches,15 while patients will often anticipate the exclusion of secondary pathology once they are referred to secondary care, and consultants will be under pressure to make a diagnosis at the first appointment.

Computed tomography versus magnetic resonance imaging

Of current guidelines for management of headache, only those from SIGN5 and the European Federation of Neurological Societies (EFNS)6 recommend a preference for either CT or MRI for investigation of headache cause:

  • SIGN:5
    • CT is recommended for unexplained neurological signs unless MRI is indicated
    • MRI is indicated for cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and headache precipitated by cough
  • EFNS—MRI is the modality of choice.6

Other guidance is available from NICE,7 the British Association for the Study of Headache (BASH),8 and the US Headache Consortium,9 but no recommendations were made on a preference for an imaging method. The decision on whether to use CT or MRI will be a function of sensitivity, side-effects, and cost. There are insufficient data to make evidence-based recommendations on the relative merit of MRI and CT in non-acute headache, but the relevant factors are:16

  • CT is cheaper and, in general, more readily available than MRI
  • CT is, theoretically, less sensitive than MRI. Although there are no direct comparisons for headache, similar populations show comparative ranges for positive findings.4 In the rare case when a tumour is missed initially on CT investigation, the clinical benefits of an earlier diagnosis in adults are likely to be marginal
  • the incidence of false positives increases almost two-fold when using MRI compared with CT
  • there has been concern over the increased use of CT and subsequent ionising radiation exposure. Although the mechanisms for quantifying radiation risks are contested, head examinations are among the lowest dose CT studies performed, with an effective radiation dose of less than 2 mSv, equivalent to less than 8 months of natural background radiation and less than the dose associated with plain image radiographs of the lumbar spine or abdomen.

Benefits of imaging

The chances of improved quality of life and length of life vary depending on the type of lesion, and in many cases improvements may be marginal. It may be reassuring for many patients and doctors if imaging is carried out to eliminate the likelihood of serious pathology. Some studies have reported variable impact on symptoms and patient anxiety levels of referral.17-19 If a patient has real concerns about what is causing their headaches, simply telling him or her that nothing is wrong will not reassure them.20 It may be worthwhile spending more time during a consultation to address those concerns, which may remove the necessity of performing unnecessary tests.21

Disadvantages of imaging

Significant anxiety can be caused by the identification on imaging of incidental pathology, which has its own clinical relevance. A recent study reported a 10% rate of incidental findings when GPs referred patients with headache for a CT scan.22 Life insurance applications in the future may also be affected by incidental findings resulting from imaging.

Flags for referral

The BASH guideline for primary care is the most appropriate for GPs because it was specifically directed at general practice and based on a combination of available evidence and expert opinion. Presentations are described as high risk, needing urgent investigation; and intermediate risk, needing careful follow up:3

  • Red flags warranting urgent investigation—probability of an underlying tumour is likely to be greater than 1% if any of the following are present:
    • papilloedema
    • headache with clinical features such as focal neurology
    • new-onset cluster headache
    • headache where abnormalities are found on neurological examination or other neurological symptoms are present
    • significant alterations in consciousness, memory, confusion, or problems with co-ordination
    • new epileptic seizure
    • cancer elsewhere in the body, especially breast and lung cancer.
  • Orange flags need careful monitoring and a low threshold for investigation should be maintained—probability of an underlying tumour is likely to be between 0.1 and 1% for headache:
    • that is new and without diagnostic pattern after 8 weeks
    • where vomiting also occurs
    • aggravated by physical exertion or Valsalva manoeuvre
    • that is longstanding, but has changed significantly, particularly if there is a rapid increase in frequency
    • that is new in a patient aged over 50 years
    • awakening from sleep.

With orange flags for isolated headache, the emphasis is on monitoring and allowing a diagnostic pattern to emerge. Headache that occurs but is not followed by development of additional signs or symptoms for a period longer than 10-12 weeks will rarely be the result of a tumour23,24 and close follow up will reduce false negatives.

Patients aged over 50 years have an increased risk of underlying pathology, and they should be monitored more closely. If no pattern to aid diagnosis has developed within 8 weeks, these patients should be considered for further investigation. The individual patient should be consulted before referring him or her for imaging, including discussion about the implications of the investigation. A patient may be more reassured by these discussions than by unnecessary tests.

Summary

In such an emotive area the decision to investigate a presentation of the headache will always be based on a discussion between the physician and patient. This article has outlined a number of important features that should alert the GP to an underlying pathology; however the problems caused by the identification of incidental pathology should not be overlooked.

Finally, it is important to emphasise that a normal investigation does not exclude the need for further follow up to identify false negatives and there may also be some important secondary causes of headache where imaging can be normal.

  • Headaches are common symptoms that often cause anxiety in both patient and doctor
  • Use of a flag system for referral can help identify individuals at risk of serious underlying pathology who need further investigation
  • Radiological investigation is the key diagnostic intervention with or without specialist neurological opinion
  • Commissioners could consider direct access to CT or MRI scans for GPs, but this should be informed by a simple care referral pathway
  • CT scans are cheaper than MRI but are less sensitive and involve a small dose of radiation (£113 including report [road-test tariff])
  • MRI scans are more sensitive, but less specific and cost more (£185 including report [road-test tariff])
  • Tariff prices for general medicine outpatient (includes cost of a scan when needed) = £214 (new), £108 (follow up) (2011–2012 road-test mandatory tariff).a

CT=computed tomography; MRI=magnetic resonance imaging

awww.dh.gov.uk/paymentbyresults/

  1. Latinovic R, Gulliford M, Ridsdale L. Headache and migraine in primary care: consultation, prescription and referral rates in a large population. J Neurol Neurosurg Psychiatry 2006; 77 (3): 385–387.
  2. Office for National Statistics. Cancer statistics registrations: Registrations of cancer diagnosed in 2008, England. MB1 39. ONS: London, 2008.
  3. Kernick D, Ahmed F, Bahra A et al. Imaging patients with suspected brain tumour. Guidance for primary care. Br J Gen Pract 2008; 58 (557): 880–885.
  4. Tsushima Y, Endo K. MR imaging in the evaluation of chronic or recurrent headache. Radiology 2005; 235 (2): 575–579.
  5. Scottish Intercollegiate Guidelines Network. Diagnosis and management of headache in adults. SIGN 107. Edinburgh: SIGN, 2008. Available at: www.sign.ac.uk
  6. Sandrini G, Friberg L, Jänig W et al. Neurophysiological tests and neuroimaging procedures in non-acute headache: guidelines and recommendations. Eur J Neurol 2004; 11 (4): 217–224.
  7. National Institute for Health and Care Excellence. Guidance on cancer services: Improving outcomes for people with brain and other CNS tumours—Analysis of the potential economic impact of the guidance. London: NICE, 2006. Available at: www.nice.org.uk/guidance/CSGBraincns/Guidance/pdf/English
  8. British Association for the Study of Headache. Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type headache, cluster headache, medication-overuse headache. 2010 edition. 3rd edition. Hull: BASH, 2010. Available at: www.bash.org.uk
  9. Frishberg B, Rosenberg J, Matchar D et al for The US Headache Consortium. Evidence-based guidelines in the primary care setting: neuroimaging in patients with nonacute headache. American Academy of Neurology, 2000. Available at: www.aan.com/professionals/practice/pdfs/gl0088.pdf
  10. Hamilton W, Kernick D. Clinical features of primary brain tumours: a case-control study using electronic primary care records. Br J Gen Pract 2007; 57 (542): 695–699.
  11. Kernick D, Stapley S, Goadsby P, Hamilton W. What happens to headache in primary care? A case controlled data base study using electronic primary care records. Cephalalgia 2008; 28 (11): 1188–1195.
  12. Suwanwela N, Phanthumchinda K, Kaoropthum S. Headache in brain tumour: a cross-sectional study. Headache 1994; 34 (7): 435–438.
  13. Grant R. Overview: brain tumour diagnosis and management: Royal College of Physicians guidelines. J Neurol Neurosurg Psychiatry 2004; 75 (suppl 2): 18–23.
  14. Iversen H, Strange P, Sommer W, Tjalve E. Brain tumour headache related to tumour size, and location. Cephalalgia 1987; 6 (Supp 7): 394–395.
  15. Kernick D, Stapley S, Hamilton W. GPs’ classification of headache: is primary headache underdiagnosed? Br J Gen Pract 2008; 58 (547): 102–104.
  16. Kernick D, Williams S. Should general practitioners have access to neurological investigation when patients present with headache? Br J Gen Pract (in press).
  17. Fitzpatrick R, Hopkins A, Harvard-Watts O. Social dimensions of healing: a longitudinal study of outcomes of medical management of headaches. Soc Sci Med 1983; 17 (8): 501–510.
  18. Howard L, Wessely S, Leese M et al. Are investigations anxiolytic or anxiogenic? A randomised controlled trial of neuroimaging to provide reassurance in chronic daily headache. J Neurol Neurosurg Psychiatry 2005; 76 (11): 1558–1564.
  19. Fitzpatrick R, Hopkins A. Referrals to neurologists for headaches not due to structural disease. J Neurol Neurosurg Psychiatry 1981; 44 (12): 1061–1067.
  20. Kessel N. Reassurance. Lancet 1979; 313 (8126): 1128–1133.
  21. Fitzpatrick R. Telling patients there is nothing wrong. BMJ 1996; 313 (7053): 311–312.
  22. Thomas R, Cook A, Main G et al. Primary care access to computed tomography for chronic headache. Br J Gen Pract 2010; 60 (575): 426–430.
  23. Vázquez-Barquero A, Ibáñez F, Herrera S et al. Isolated headache as the presenting clinical manifestation of intracranial tumors: a prospective study. Cephalalgia 1994; 14 (4): 270–272.
  24. Kernick D, Stapley S, Goadsby P, Hamilton W. What happens to new-onset headache presented to primary care? A case-cohort study using electronic primary care records. Cephalalgia 2008; 28 (11): 1188–1195. G