REVIEWPract Neurol 2009; 9: 80–84

Not all morningheadaches aredue to braintumoursA J Larner

A J LarnerConsultant Neurologist, Walton

Centre for Neurology and

Neurosurgery, Lower Lane,

Fazakerley, Liverpool L9 7LJ, UK;

a.larner@thewaltoncentre.nhs.uk

Headaches causing early morning waking, or headaches which are moreprominent on waking, always raise the suspicion of raised intracranialpressure, and hence the need for prompt evaluation to exclude the diagnosisof a brain tumour (particularly if they are associated with vomiting andpapilloedema). However, there are many other much more common causes of‘‘morning headache’’, both primary and secondary. As ever, history taking iskey to the diagnosis. Attention to the possibility of analgesic medicationoveruse is particularly pertinent, but other treatable conditions such asdepression and epilepsy must not be overlooked.

Classical clinical teaching, familiar to

practically all doctors and drummed

into all medical students, is that one

of the features of raised intracranial

pressure (ICP) is headache which causes

nocturnal or early morning waking, and/or is

worse on waking, then declining in severity

after getting up. This nocturnal or early

morning headache is thought to reflect

exacerbation of raised ICP through recum-

bency, nocturnal hypoventilation with a rise

in PaCO2 and cerebral vasodilatation,1 and

possibly increased brain metabolism during

REM (rapid eye movement) sleep.2 Such

headaches are almost invariably associated

with papilloedema, and sometimes with

vomiting which may lead to hyperventilation

and reduction of ICP. In the UK, headache

with vomiting and papilloedema is enshrined

in Department of Health guidelines for

urgent evaluation (the ‘‘two-week rule’’),

although in practice very few patients

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referred under these guidelines have such

features, or indeed cerebral tumours.3 In fact,

any patient with all three features should be

seen immediately, certainly not wait for even

two weeks, because they may very well have

raised ICP.

So, are all morning headaches due to brain

tumours with raised ICP? Clearly not, but

neurologists are often referred patients with a

history of nocturnal and/or awakening head-

aches—‘‘query raised ICP’’, in the apparent

absence of other neurological symptoms and

signs. The differential diagnosis is in fact

quite broad (see box), encompassing not only

intracranial hypertension but also a number

of primary and secondary headache disorders,

as well as general neurological, medical and

psychiatric conditions.

PRIMARY HEADACHEDISORDERSMigraineThere is a circadian variation in migraine

onset, with preferential (but not exclusive)

onset in the night or early morning, between

04:00 h and 09:00 h.4 There is an older

literature devoted to ‘‘nocturnal migraine’’

and ‘‘early morning migraine’’, although there

is no reason to believe that these forms differ

from migraine at any other time of day.

Trigeminal autonomiccephalalgiasCluster headache, the most common of the

trigeminal autonomic cephalalgias, is char-

acterised not only by its unilaterality and

associated autonomic symptoms and signs

but also by its periodicity, the attacks often

recurring at the same time of the day or

night, with perhaps 50% of patients reporting

attack onset during the night. For this reason,

it is sometimes known as ‘‘alarm clock

headache’’ (compare with hypnic headache

below). Nocturnal cluster headache attack

onset is said to be more predictable than

daytime attack onset.5

Other disorders falling within the trigem-

inal autonomic cephalalgia category may also

present with nocturnal attacks, but prepon-

derance of nocturnal rather than daytime

attacks is rare in both paroxysmal hemicrania6

and short-lasting unilateral neuralgiform

headache attacks with conjunctival injection

and tearing (SUNCT).7 In both these condi-

tions, attacks may occur throughout the

24-hour period.

Hemicrania continuaThe precise nosological position of hemicrania

continua is still debated. Although not

Differential diagnosis of nocturnal and/or awakeningheadaches

Raised intracranial pressurel Neoplasml Intracranial hypertension secondary to hydrocephalus

Primary headache disordersl Migrainel Trigeminal autonomic cephalalgias

– Cluster headache– Paroxysmal hemicrania– Short-lasting unilateral neuralgiform headache attacks with conjunctival– injection and tearing (SUNCT)

l Hemicrania continual Hypnic headachel Primary headache associated with sexual activity

Secondary headache disordersl Medication-overuse headachel Hangover headachel Giant cell (temporal) arteritisl Sphenoid sinusitisl Carbon monoxide-induced headachel Subarachnoid haemorrhage

Other disordersl Headache attributed to epileptic seizurel Sleep apnoea hypopnoea headachel Depressionl Exploding head syndrome

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currently classified with the trigeminal

autonomic cephalalgias in the International

Headache Society schema (ICHD2),8 it has

certain features in common with them,

including autonomic manifestations and

indomethacin responsiveness as seen in

paroxysmal hemicrania. Pain is, by definition,

daily and continuous, but exacerbations may

occur and these frequently awaken the

patient from sleep.

Hypnic headacheA defining characteristic of this rare primary

headache disorder is onset during sleep,

usually at a consistent time each night,

between 01:00 h and 03:00 h, hence it too

has sometimes been known as ‘‘alarm clock

headache’’ (cluster headache is another

‘‘alarm clock headache’’, see above).

Recurrent attacks of headache occur, often

in the middle or later stages of sleep, possibly

emerging during REM sleep.9 The pathogen-

esis remains unknown but may be related to

impaired inactivation of anti-nociceptive

brain structures, such as the locus coeruleus

which is normally inactivated during REM

sleep. Differentiating factors from cluster

headache include frequently bilateral headache,

the absence of autonomic features, onset in

later life, and female preponderance.10

Primary headache associatedwith sexual activityThe primary headache disorder associated

with sexual activity, previously known as

coital or orgasmic cephalalgia, may resemble

subarachnoid haemorrhage at onset,

although vomiting and loss of consciousness

are very unusual. The patients are typically

males. There are no specific data, but it would

seem likely that most episodes occur during

the evening or night hours (although the

patients are clearly not asleep). The mean age

of onset was 39 years in a series of patients

attending a dedicated headache clinic,11 and

the age range in a series presenting to general

neurology clinics was 19–56 years (mean 42

years).12 These data, admittedly from biased

samples, suggest that it is generally not

individuals in the first flush of sexual vigour

but those of a certain maturity who are most

likely to be both affected and to consult; a

group whose sexual activities may, for various

domestic and occupational reasons, be

restricted to certain times of the day, or

more precisely, night.

SECONDARY HEADACHEDISORDERSMedication-overuse headacheThe scenario of recurrent generalised head-

aches associated with escalating analgesic use,

is perhaps one of the most familiar in the

neurology clinic. Not infrequently there is a

clear history of headache waking the patient

during the night, often with the desire to

consume further analgesics. My experience

suggests that this is the most common cause of

nocturnal headache seen in general neurology

outpatient clinic practice, far exceeding either

raised intracranial pressure or cluster headache,

and on occasion being referred under the ‘‘two-

week rule’’ CNS/brain tumour guidelines.3

Hangover headacheDiagnosis of hangover headache (‘‘delayed

alcohol-induced headache’’ is the preferred

ICHD2 terminology8) should be obvious from

the history.

Giant cell (temporal) arteritisThe headache associated with giant cell

arteritis is acknowledged to be highly variable,

but when present it is often persistent and

worse at night,13 perhaps because of contact

between the pillow and tender, inflamed scalp

arteries.

Sphenoid sinusitisHeadache is the most common symptom of

acute sphenoid sinusitis (or ‘‘rhinosinusitis’’,

as in the ICHD2 classification,8 as sinusitis in

the absence of rhinitis is uncommon) often

interfering with sleep. It is rare, particularly in

isolation, and misdiagnosis common. The pain

is severe, intractable, not specifically localised,

sometimes aggravated by bending or cough-

ing, not relieved by simple analgesics, and

may be associated with facial pain. Diagnosis

may be difficult because not all patients have

pyrexia or purulent nasal discharge.14 As the

condition has potential morbidity and mor-

tality, it is very important not to miss it.

Diagnostic investigations include CT, MRI and

fibreoptic nasal endoscopy.

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Carbon monoxide-inducedheadacheClassically carbon monoxide-induced head-

ache has been described as a throbbing

diffuse headache, but systematic studies have

found this to be rare. In fact, the associated

headache is very variable in nature, with no

particular features allowing diagnosis or

exclusion.15 Carbon monoxide-induced head-

ache is seasonal, being more common in the

winter months when (faulty) gas heating

systems are in use, and cohabitants may also

have headache. People in small enclosed

spaces such as caravans and boats are

particularly likely to be affected.

Subarachnoid haemorrhageOnset of subarachnoid haemorrhage during

sleep is extremely rare, if it occurs at all. The

history here is critical, particularly whether the

patient was actually asleep, because headache

secondary to sexual activity enters the differ-

ential. Stroke apparent on awakening is more

likely to be ischaemic than haemorrhagic.16

OTHER DISORDERSEpilepsyNocturnal seizures may present with morning

headache. Although the history should clearly

indicate this diagnosis, absence of a bed

partner may mean that the diagnosis is

delayed, as exemplified by the case of a 65-

year-old single lady referred to my clinic with

a diagnosis of migraine, who gave a five-year

history of occasional (approximately monthly)

headaches present only on waking and which

gradually cleared over the course of the

morning. She also mentioned that on occa-

sion she had noticed blood on her pillow on

‘‘headache mornings’’ because she had bitten

her tongue, and on two occasions she had

wet the bed as well. The headache was an

oppressive, dopey sensation precluding atten-

dance at work, and sometimes associated

with the need for daytime sleep. A provisional

diagnosis of nocturnal (secondary general-

ised) seizures was made, but the patient

declined antiepileptic drug treatment pending

further investigation. The EEG was abnormal

with predominantly left-sided slow wave

activity, and occasional sharp wave dis-

charges over both temporal regions, suggest-

ing a potential epileptogenic focus in the left

(and possibly right) temporal region. Before

her follow-up appointment was due, the

patient was found dead in bed one morning,

perhaps as the consequence of a seizure.

Other clues to the diagnosis of nocturnal

seizures are waking up on the floor, and

dishevelled bedclothes.

Obstructive sleep apnoeahypopnoea syndromeEarly morning headache has been cited as a

feature of the obstructive sleep apnoea

hypopnoea syndrome, presumably due to

nocturnal hypercapnia secondary to alveolar

hypoventilation with resultant intracranial

vasodilatation. Although encountered on occa-

sion in the neurology clinic,17 some authorities

with extensive experience of this syndrome say

early morning headache is in fact rare.18

Moreover, the situation may be confounded,

because sleep disturbance is a migraine trigger

and, possibly, by sleep apnoea per se being a

risk factor for cluster headache.19

DepressionEarly morning waking is one of the classic

vegetative symptoms of depression, often in

association with depressive thinking.

Although headache is not a feature of

depressive disorders as enshrined in the

Diagnostic and Statistical Manual (DSM-IV)

criteria, it should not be forgotten that this

symptom is not uncommon in clinical

practice. Moreover, mood disorders can

complicate migraine and possibly chronic

tension type headache, and hence need to

be identified and treated in their own right.

PRACTICE POINTS

l Patients with headaches which wake them during the night or are presenton waking and improve after getting up, and who have associatedpapilloedema and vomiting, require immediate assessment because theymay have raised intracranial pressure.

l Many other and more common conditions may also be associated withnocturnal or early morning headaches.

l The chronobiology of many primary headache disorders has a circadianpattern with preferential headache timing during the night or earlymorning, including migraine, cluster headache and hypnic headache.

l Medication overuse headache is a common cause of nocturnal headache,with the patient waking to consume more analgesia.

l Non-headache disorders such as depression and nocturnal epilepticseizures also enter the differential diagnosis.

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Headache patients with depression (and

anxiety) have greater functional impairment

than those without.20

Exploding head syndromeThe precise nosological position of this

condition is uncertain. It may be regarded

as a physiological phenomenon in the transi-

tion from wakefulness to sleep, akin to

nocturnal myoclonus. Although said to be

quite common,21 it is seldom a presenting

symptom in the neurology clinic.

CONCLUSIONSAlthough raised ICP is the most alarming

possible cause of nocturnal and/or awakening

headaches, the sensitivity and specificity of

this symptom for the diagnosis of intracranial

hypertension has not, to my knowledge, been

systematically evaluated. ICHD2 lists only two

categories in which headache ‘‘worse in the

morning’’ is included among the diagnostic

criteria, namely ‘‘Headache attributed directly

to neoplasm’’ and ‘‘Headache attributed to

intracranial hypertension secondary to hydro-

cephalus’’.8 However, ‘‘morning headaches’’

may occur with other causes of raised ICP—

for example, the headache of idiopathic

intracranial hypertension may awaken the

patient at night.22 Nocturnal and/or awaken-

ing headache is clearly not a pathognomonic

symptom for raised ICP, far from it. Many

other headache disorders, some very common

such as migraine, as well as other neurolo-

gical and medical conditions enter the

differential diagnosis. History taking is key

to identifying them,23 and hence determining

the most appropriate pathway for investiga-

tion (if any) and management.

ACKNOWLEDGEMENTSThis article was reviewed by David Hilton-

Jones, Oxford, UK.

REFERENCES1. North B, Reilly P. Raised intracranial pressure. A

clinical guide. Oxford: Heinemann, 1990:26–8.

2. Cooper R, Hulme A. Intracranial pressure and

related phenomena during sleep. J NeurolNeurosurg Psychiatry 1966;29:564–70.

3. Abernethy Holland AJ, Larner AJ. Central nervous

system/brain tumour 2-week referral guidelines:

prospective 3-year audit. Clin Oncol 2008;20:201–2.

4. Fox AW, Davis RL. Migraine chronobiology.

Headache 1998;38:436–41.

5. Bahra A, May A, Goadsby PJ. Cluster headache: a

prospective clinical study with diagnostic

implications. Neurology 2002;58:354–61.

6. Kayed K, Godtlibsen OB, Sjaastad O. Chronic

paroxysmal hemicrania IV: ‘‘REM sleep locked’’

nocturnal attacks. Sleep 1978;1:91–5.

7. Cohen AS, Matharu MS, Goadsby PJ. Short-lasting

unilateral neuralgiform headache attacks with

conjunctival injection and tearing (SUNCT) or

cranial autonomic features (SUNA): a prospective

clinical study of SUNCT and SUNA. Brain2006;129:2746–60.

8. International Headache Society Classification

Subcommittee. The international classification of

headache disorders. Second edn. Cephalalgia2004;24(Suppl 1):1–160.

9. Dodick DW, Mosek AC, Campbell JK. The hypnic

(‘‘alarm clock’’) headache syndrome. Cephalalgia1998;18:152–6.

10. Evers S, Goadsby PJ. Hypnic headache. Neurology2003;60:905–9.

11. Frese A, Eikermann A, Frese K, et al. Headache

associated with sexual activity. Demography,

clinical features, and comorbidity. Neurology2003;61:796–800.

12. Larner AJ. Late presentation of primary headache

associated with sexual activity: is non-invasive

angiography worthwhile? J Headache Pain2006;7:139–40.

13. British Association for the Study of Headache.

Guidelines for all healthcare professionals in the

diagnosis and management of migraine, tension-

type, cluster and medication-overuse headache.

BASH: London, 2007:17.

14. Lew D, Southwick FS, Montgomery WW, et al.Sphenoid sinusitis: a review of 30 cases.

N Engl J Med 1983;319:1149–54.

15. Hampson NB, Hampson LA. Characteristics of

headache associated with acute carbon monoxide

poisoning. Headache 2002;42:220–3.

16. Wroe SJ, Sandercock P, Bamford J, et al. Diurnal

variation in incidence of stroke: Oxfordshire

community stroke project. BMJ 1992;304:155–7.

17. Larner AJ. Obstructive sleep apnoea syndrome

presenting in a neurology outpatient clinic. Int J ClinPract 2003;57:150–2.

18. Stradling JR. Sleep apnoea syndromes. In: Brewis

RAL, Corrin B, Geddes DM, Gibson GJ, eds.

Respiratory medicine. Second edn. WB Saunders:

London, 1995:973–1005.

19. Rains JC, Poceta JS. Sleep-related headache

syndromes. Semin Neurol 2005;25:69–80.

20. Page LA, Howard LM, Husain K, et al. Psychiatric

morbidity and cognitive representations of illness

in chronic daily headache. J Psychosom Res2004;57:549–55.

21. Pearce JM. Clinical features of the exploding head

syndrome. J Neurol Neurosurg Psychiatry1989;52:907–10.

22. Wall M. The headache profile of idiopathic

intracranial hypertension. Cephalalgia1990;10:331–5.

23. Davenport R. Headache. Pract Neurol2008;8:335–43.

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