Migraine Headache Differential Diagnoses

Updated: Apr 18, 2023
  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Helmi L Lutsep, MD  more...
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Diagnostic Considerations

When headache is episodic and recurrent and follows a well-established pattern, the patient likely has a primary headache disorder (ie, headaches with no organic or structural etiology). Differentiating migraine from other primary headaches (eg, muscle contraction tension headache, cluster headache) is important, as optimal treatment may differ.

Migraine may also may simulate or be simulated by secondary headache disorders or coexist with a secondary headache disorder. Any of the following features suggest a secondary headache disorder and warrant further investigation:

  • The first or worst headache of the patient's life, especially if rapid in onset

  • A change in frequency, severity, or clinical features of the attack

  • New progressive headache that persists for days

  • Precipitation of headache with Valsalva maneuvers (ie, coughing, sneezing, bearing down)

  • The presence of associated neurologic signs or symptoms (eg, diplopia, loss of sensation, weakness, ataxia)

  • Onset of headaches after the age of 55 years

  • Headache developing after head injury or major trauma

  • Persistent, 1-sided throbbing headaches

  • Headache accompanied by stiff neck or fever

  • Atypical history or unusual character that does not fulfill the criteria for migraine

  • Inadequate response to optimal therapy

Crash migraine

Severe headache of sudden onset is a concern despite its occurrence in primary headache disorders. Migraine headaches may have an abrupt onset; these are termed "crash" migraine headaches and are similar to a "thunderclap" headache. Cluster headache also may be sudden and excruciating, but it lasts only 15-180 minutes and is recognized easily if the patient has had previous attacks.

Exertional headache

Exertional headaches are precipitated by strenuous activity (eg, running, coughing, sneezing, Valsalva maneuver) and build in intensity over minutes. They are particularly common in patients who have an inherited susceptibility to migraine. Coital headache is a type of exertional headache that can develop at the height of orgasm or it may build up through intercourse.

Intracranial aneurysm

Despite the possibility of a benign cause, a ruptured intracranial aneurysm is the primary consideration if the headache is severe and of sudden onset and reaches maximum intensity in minutes. The classic presentation of an aneurysmal subarachnoid hemorrhage (SAH) is as follows:

  • Severe headache with sudden, explosive onset

  • Stiff neck

  • Photophobia

  • Nausea and vomiting

  • Possibly, alteration of consciousness

An extensive evaluation is indicated in such cases, including an initial computed tomography (CT) scan of the head without contrast. Lumbar puncture (LP) should be considered if the scan is negative, as 25% of cases are missed by CT scanning. Questions remain over whether an angiogram should be performed if the patient has normal findings on neurologic and cerebrospinal fluid (CSF) examination, as well as on CT scan or MRI.

In one study, acute, severe thunderclap headache comparable to that of SAH without the nuchal rigidity occurred in 6.3% of patients with unruptured aneurysm. Other studies have revealed that in patients with severe thunderclap headache with normal CT-scan and CSF findings, none developed SAH. [73]

In selected cases, angiography should probably be performed if an experienced angiographer is available. Patients at risk include those whose CT scan and LP are performed late after symptom onset, so that negative results are unreliable, and patients with suggestive clinical features, such as family history or past medical history of SAH, classic SAH-like symptoms, or the presence of neurologic signs (in particular a third cranial nerve palsy affecting the pupil)

In patients with unrevealing studies in whom the diagnosis of aneurysmal SAH is possible but very unlikely, MRI and magnetic resonance angiography (MRA) are screening tests. Close follow-up is appropriate if the findings of these tests are negative.

Space-occupying lesion

Another concern is the possibility of a space-occupying lesion mimicking migraine. In a series of 111 patients with primary (34%) or metastatic (66%) brain tumor, headache was reported in 48%; the headache had characteristics similar to migraine in 9% and to tension-type headache in 77%, while the so-called classic early morning brain tumor headache occurred in only 17%. Headache was intermittent in 62%, usually lasting a few hours. [74]

All patients with headaches similar to migraine had other neurologic symptoms or abnormal signs. Of note is that 32% of the patients had a history of headache; in 36% of those patients, the headache was of identical character to prior headaches but was more severe or frequent and was associated with other symptoms, such as seizures, confusion, prolonged nausea, and hemiparesis. [74]

These data indicate that patients with a history of headache should have further diagnostic workup if the headache is accompanied by new symptoms or abnormal signs or differs in any way from their usual headache. With new-onset headache, imaging should be obtained if headache is severe or occurs with nausea, vomiting, or abnormal signs.

Other space-occupying lesions must be considered in the appropriate clinical setting. Large intraparenchymal hemorrhage presents dramatically with headache and neurologic symptoms or signs shortly after onset. Of patients with chronic, subacute, or acute subdural hematoma, 81%, 53%, and 11%, respectively, have headaches. In brain abscesses, a progressive, severe, intractable headache is common, and headache is reported in 70-90% of patients.

Cerebral venous thrombosis

Cerebral venous thrombosis involves the sagittal sinus in about 70% of cases; these patients present with signs and symptoms of increased intracranial pressure (ICP), such as headache and papilledema. Should the thrombus extend to the superficial cortical veins, then focal findings may be noted. In the appropriate setting with known risk factors, cerebral venous thrombosis must be considered, with the patient evaluated with MRI, MRA, or magnetic resonance venography (MRV).

Spontaneous internal carotid artery dissection

Spontaneous internal carotid artery dissection is an uncommon cause of headache and acute neurologic deficit, but it must be considered in younger patients who have unilateral, severe, persistent head pain of sudden onset preceding the development of neurologic signs, most commonly Horner syndrome. This differentiates spontaneous from posttraumatic cases, in which cerebral ischemic symptoms are more common.

Other secondary causes

Other secondary causes of alarming headaches should be sought, in the proper clinical setting, in the presence of the "red flags" mentioned above. Increased ICP may result from colloid cysts, ventricular tumors (such as ependymomas), or Chiari malformations. Other features needing further diagnostic workup include positional headaches, which may result from low CSF pressure.

Headaches after age 50 years must be investigated to consider temporal or giant cell arteritis. Headaches associated with systemic disease require consideration of infectious and noninfectious inflammatory processes.

Bear in mind that response to 5-hydroxytryptamine–1 (5-HT1) agonists (sumatriptan and related compounds) is not diagnostic of a migraine headache. Because of their ability to block expression of c-fos by their action on 5-HT1 receptors, these agents may be effective in decreasing headache pain associated with meningovascular irritation from a variety of causes, such as viral and bacterial infections and subarachnoid hemorrhage.

Differential Diagnoses