Differentials

Tension-type headache (TTH)

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Frequently coexists with migraine in the same patient.[57]

TTH is common, but rarely causes patients to seek medical care, unless it is very frequent and severe. Patients diagnosed with TTH in primary care may have migraine.

Attacks are generalised throughout the head; often bilateral pressure-like and non-throbbing pain.[58]​ Often described as feeling like a tight band around the head.

Unlike with migraine, symptoms of TTH are not aggravated by physical activity.[39]

Tension headaches rarely have photophobia or phonophobia (and cannot have both; otherwise it is a migraine).[3]

The distinction is best made by taking a careful history and having the patient keep a diagnostic headache diary.

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There are no differentiating tests.

Cluster headache

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Cluster headache is rare. It is more common in men; by contrast, migraine is more common in women.[59]

Cluster headache causes extremely severe pain around only one eye, becomes maximally severe in a few minutes, and does not switch side.

Attacks last up to 3 hours (differentiating feature as migraine can last 4-72 hours) and cause restlessness and agitation (in contrast with migraine, where pain often worsens with routine physical activity), with autonomic signs or symptoms on the side of the pain.[3]

Cluster attacks can occur up to 8 times per day, with intervals of no headache between attacks.[3]

The cluster period usually lasts for several weeks, and often occurs at the same time during the year. Attacks may occur at exactly the same time of the day or night, especially during rapid eye movement sleep.[60]

The distinction is best made by taking a careful history and having the patient keep a diagnostic headache diary.

Cluster headache may occur in patients with migraine. The very short duration of headache relative to migraine, combined with several attacks per day, and restlessness during an attack, differentiates migraine and cluster headache.

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There are no differentiating tests.

Medication overuse headache

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This headache has a mixed picture of both migraine and tension-type features. It occurs on 15 days/month or more in a patient with a pre-existing headache disorder.[3]​ It may develop from overuse of acute medication to treat migraine attacks.[39]

Can be globalised and associated with nausea. Characterised by regular medication overuse for at least 3 months.[3]

Because they are available without a prescription, over-the-counter non-steroidal anti-inflammatory drugs and aspirin, especially aspirin/paracetamol/caffeine combinations, are common causes of medication-overuse headache.

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There are no differentiating tests.

Headache after head or neck trauma

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Post-traumatic headaches can mimic most forms of primary headache, including migraine.

In a patient with a prior history of migraine, worsening of headache in response to head trauma is considered to be an aggravation of migraine.

Diagnosis is made on the basis of the history. Post-traumatic headache is diagnosed only when a new type of headache begins for the first time within 7 days of head or neck injury.[3]

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There are no differentiating tests.

Subarachnoid haemorrhage (SAH)

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SAH is commonly a severe, sudden-onset headache (thunderclap headache), although up to 50% of patients may have a prodrome of a lower-grade 'sentinel' headache.[61]

As with migraine, analgesics or triptans may improve the pain.[62]

The physical examination may be normal, although up to 25% of patients have neurological findings.[61]

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Plain CT scans can detect the presence of gross blood, but if CT is negative, consider lumbar puncture in patients with a history strongly suggestive of SAH. Angiography may be needed.[42][46][61]

Cerebral neoplasm

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While headache is a common symptom in patients with cerebral neoplasms, it has no consistent characteristics and rarely occurs in the absence of other suspicious historical or examination features.

Suspicion is increased in patients with a progressive pattern of headache worsening in conjunction with the development of new neurological signs or symptoms.

Papilloedema on fundoscopic examination should prompt consideration of a neoplastic or other cause of high cerebrospinal fluid pressure.[63]

INVESTIGATIONS

CT or MRI scans may identify space-occupying lesions.

Low-pressure headache

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Headache attributed to low cerebrospinal fluid pressure is often worsened with standing and improved with lying down.[3]​​

It can result from a spontaneous or iatrogenic dural tear; for example, following craniotomy or epidural analgesia.

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The diagnosis of low-pressure headache can be very difficult if the dural tear occurred spontaneously. Lumbar puncture may show a low opening pressure, and MRI scans of the brain with gadolinium may demonstrate pachymeningeal enhancement.[64] Spinal myelogram with CT imaging may demonstrate contrast extravasation.[65]

High-pressure headache (idiopathic intracranial hypertension)

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Historical and physical examination features suggestive of headaches due to idiopathic intracranial hypertension include visual disturbances, tinnitus, and the finding of papilloedema on ophthalmological examination.

High cerebrospinal fluid pressure can result from intracranial pathology, such as cerebral neoplasms, or from idiopathic intracranial hypertension (IIH).[3]

IIH is most common in obese women of childbearing age and is also associated with the use of certain antibiotics and oral contraceptives.[66]

INVESTIGATIONS

Lumbar puncture (LP) may show a high opening pressure, but must not be done in the presence of papilloedema until an imaging study has been performed. LP must be performed with the patient in an appropriate position (lateral decubitus), with careful measurement of cerebrospinal fluid pressure.[67]

Central nervous system (CNS) infection

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Headache is a common feature of CNS infections, and has no consistent clinical characteristics.

The diagnosis is straightforward in the presence of a high fever or altered consciousness. Indolent CNS infections, however, can be more difficult to diagnose.

Suspicion for these disorders should be increased in patients with immune compromise that predisposes to infection with Toxoplasma gondii, Cryptococcus, or cytomegalovirus.

INVESTIGATIONS

Culture and microscopy of cerebrospinal fluid and samples from other potential sites of infection may identify the infecting micro-organism.

Giant cell arteritis

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Giant cell arteritis should be considered in patients over the age of 50 years with new-onset or worsening headache.

It is most common in people of northern European descent.[68]

If untreated, permanent visual loss can occur.

The headache has no characteristic features, but it commonly improves or disappears within 3 days of beginning high-dose corticosteroid treatment.[3]

Historical features include a history of jaw claudication, muscle pain, and a tender temporal artery.[45][68]​​

INVESTIGATIONS

Elevated erythrocyte sedimentation rate (>100 mm/hour) and/or elevated C-reactive protein is associated with giant cell arteritis; biopsy of temporal artery shows typical inflammatory infiltrate.[45] Ultrasound can detect pathological changes in other cranial arteries than the temporal artery.[69]

Arterial dissection

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Headache and/or neck pain occurs in more than 50% of cases of cervical artery dissection. This is the most frequent initial symptom (33% to 86% of cases) and can occasionally be the only symptom. A severe acute migraine in the setting of neck pain may indicate an increased risk for cervical artery dissection, resulting in stroke.[70]

The headache has no consistent features, and can mimic primary headache disorders or present as a sudden, severe thunderclap headache.[71]

Headache is usually found on the same side as the dissection and can occur with Horner's syndrome or tinnitus.[72]

INVESTIGATIONS

Angiography may demonstrate the lesion.

Cerebral venous thrombosis (CVT)

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Headache is the most common symptom (80% to 90% of cases) and the most common initial symptom in CVT.

The headache has no specific characteristics, can mimic any of the primary headache disorders, and can be a sudden-onset, severe thunderclap headache.[73]

In 90% of patients, CVT is associated with focal neurological signs and evidence of idiopathic intracranial hypertension.[73]

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Neuroimaging (magnetic resonance venogram) is generally necessary for definitive diagnosis.[74]

Ischaemic stroke

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Headache can be a symptom of ischaemic stroke. Migraine, particularly with aura, is an independent risk factor for ischaemic stroke, with highest risk in women aged under 45 years.[75]

Neurological deficit in stroke or transient ischaemic attack (TIA) is usually maximal at onset and lasts longer than an hour.[76]

Migraine aura can be confused with ischaemic stroke or TIA, but typically develops gradually, consists of positive and negative symptoms with no relevant imaging abnormalities, and is fully reversible.[4]

INVESTIGATIONS

CT scans or MRI scans may detect ischaemic lesions.

Reversible cerebral vasoconstriction syndrome (RCVS)

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RCVS is associated with repeated thunderclap headaches, rather than one prolonged severe headache as seen in migraine.[77]

RCVS causes short irregular segments of vasoconstriction in small arteries, in an asymmetrical distribution. It is often associated with convexity subarachnoid haemorrhage, rather than basilar subarachnoid haemorrhages, and can be associated with ischaemic stroke.[78]

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CT followed by lumbar puncture is used to rule out subarachnoid haemorrhage. MR angiography or CT angiography can visualise vasoconstriction in cerebral arteries.

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