Acute Headache: Diagnosis by Stephanie J Nahas MD (Dr

Acute headache: diagnosis By Stephanie J Nahas MD (Dr. Nahas of Thomas Jefferson University has no relevant financial relationships to disclose.) Originally released October 21, 2004; last updated December 4, 2017; expires December 4, 2020

Introduction

This article incudes discussion of diagnosis of acute headache; migraine; thunderclap headache; tension-type headache; headache with systemic illness or systemic symptoms; migraine aura; headache triggered by cough, exertion, or orgasm; headache during pregnancy or postpartum; positional headache; headache in the elderly; sinus symptoms and headache; and ocular disorders. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Headache is a common chief complaint in acute settings. The diagnosis of acute headache can be challenging and should proceed in an orderly fashion. An important first step is to distinguish primary from secondary headaches. The approach is to seek “red flags” that suggest the possibility of secondary headache. If 1 of these features is identified, the physician must conduct the workup indicated by the red flag and, thereby, diagnose any secondary headache disorder that is present. In the absence of secondary headache, the clinician proceeds to diagnosing a primary headache disorder. In this article, the author follows this approach to discuss the differential diagnosis of acute headaches.

Key points • Migraine is the most common diagnosis in the evaluation of acute headache. • Secondary causes must be ruled out in all cases of acute headache presentation, mainly based on “red flags” uncovered in the history and physical/neurologic examination. • A systematic approach to the headache, characterizing it in terms of duration, quality, location, and accompanying symptoms, speeds the diagnosis.

Headache classification

Headache is a common type of recurrent pain and 1 of the most frequent symptoms in neurology. Although virtually everyone gets occasional headaches, there are well-defined headache disorders that vary in incidence, prevalence, and duration (Robbins and Lipton 2010).

Before 1988, the headache classification systems that were available did not have clear operational rules, and nomenclature varied widely. In 1988, the International Headache Society instituted a classification system that has become the standard for headache diagnosis and, particularly, for clinical research (Headache Classification Committee of the International Headache Society 1988). The 2nd edition of the International Classification of Headache Disorders (ICHD-2) was released in September of 2004 (Headache Classification Committee of the International Headache Society 2004), and the 3rd edition (ICHD-3 beta) was issued in July 2013 (Headache Classification Committee of the International Headache Society 2013). According to this system, headaches are divided into 2 broad categories: primary headache disorders and secondary headache disorders. In secondary disorders, headaches are attributed to another condition, such as a brain tumor, infection, or head injury; for the primary disorders, no specific cause can be found.

Headache is the fifth most common chief complaint in the emergency department in about 2% of patients, or 2 million visits annually in the United States (Goldstein et al 2006). Internists and neurologists are often called to evaluate, or are consulted by, patients during a headache attack. The diagnosis of acute headache is challenging and should proceed in an orderly fashion. Crucial elements include a thorough history, supplemented by general medical and neurologic examinations, and laboratory testing and neuroimaging of selected patients. Approaching a patient with acute headache

An important first step in acute headache diagnosis is to distinguish a primary from a secondary headache. Most patients who have an acute headache have a primary headache disorder (Friedman and Lipton 2011), but the probability of secondary headaches increases in the emergency department.

Certain “red flags” suggest the possibility of secondary headache. Once these features are identified, the physician must conduct the workup indicated by the red flag (Table 1) and diagnose the secondary headache disorder if one is present.

Table 1. Red Flags in the Diagnosis of Headache Red flag Consider Possible investigations Sudden-onset headache • Subarachnoid hemorrhage, • Neuroimaging first and foremost • Lumbar puncture (after • See Table 2 for differential neuroimaging evaluation) diagnosis Worsening headache pattern • Mass lesion • Neuroimaging • Subdural hematoma • Medication overuse Headache with cancer, HIV, or • Meningitis • Neuroimaging other systemic illness (fever, neck • Encephalitis • Lumbar puncture stiffness, cutaneous rash) • Lyme disease • Biopsy • Systemic infection • Blood tests • Collagen vascular disease • Arteritis Focal neurologic signs or • Mass lesion • Neuroimaging symptoms other than typical • AVM • Collagen vascular evaluation visual or sensory aura • Collagen vascular disease Papilledema • Mass lesion • Neuroimaging • Idiopathic intracranial • Lumbar puncture (after hypertension neuroimaging evaluation) • Encephalitis • Meningitis Triggered by cough, exertion, or • Subarachnoid hemorrhage • Neuroimaging Valsalva • Mass lesion • Considerer lumbar puncture • Posterior fossa pathology Headache during pregnancy or • Cortical vein or cranial • Neuroimaging postpartum sinus thrombosis • Carotid dissection • Pituitary apoplexy

Modified from: (Lipton et al 2008)

Table 2. Differential Diagnoses of Thunderclap Headache Vascular etiologies Subarachnoid hemorrhage Cervical artery dissection Aneurysmal thrombosis or expansion Cerebral venous thrombosis Hypertensive crisis Reversible cerebral vasoconstriction syndrome (especially for recurrent thunderclap headache) Pituitary apoplexy Retroclival hematoma Nonvascular etiologies Spontaneous intracranial hypotension/hypovolemia Colloid cyst of the third ventricle Meningitis Sinusitis (especially sphenoid) Primary cough, sexual, and exertional headache Primary thunderclap headache (idiopathic)

Identifying secondary headaches

Herein we discuss common red flags, the differential diagnoses suggested by these red flags, and the appropriate investigation required by each one. It is important to emphasize that red flags indicate an increased probability of secondary headache. The presence of a red flag increases the need to perform further investigation, but the patient must be analyzed in the context of the overall clinical picture. Certain “comfort signs,” such as acknowledgement of a typical headache trigger, a family history of similar headaches, or the presence of typical signs and symptoms of a primary headache disorder may offset minor red flags. Some clinical scenarios may prompt the clinician to ascribe a secondary diagnosis erroneously, leading to incorrect treatment.

(1) Sudden onset of severe headache (thunderclap headache). The sudden onset of a severe (explosive) headache must be investigated. Although it is not the most common cause of thunderclap headache, subarachnoid hemorrhage is the most feared. A meta-analysis showed that 10% to 43% of patients with subarachnoid hemorrhage demonstrate thunderclap headaches (incidence varies in different settings) (Polmear 2003). More studies have also identified the following features as predictive of subarachnoid hemorrhage: age greater than 40, witnessed loss of consciousness, neck stiffness, onset during exertion, vomiting, blood pressure greater than 160/100, and arrival by ambulance (Perry et al 2010; Perry et al 2013). All patients with thunderclap headache should have an expedient and exhaustive search for an underlying cause. These include serious intracranial vascular disorders, such as aneurysmal subarachnoid hemorrhage, intracerebral hemorrhage, cerebral venous (or sinus) thrombosis, arteriovenous malformation, arterial dissection (intra- and extracranial), CNS angiitis, pituitary apoplexy, and reversible cerebral vasoconstriction syndrome, which is increasingly recognized as a cause of recurrent thunderclap headaches (Calabrese et al 2007; Sheikh and Mathew 2014). Other organic causes of thunderclap headache are colloid cysts of the third ventricle, CSF hypotension, acute sinusitis (particularly with barotrauma), and meningoencephalitis (Ju and Schwedt 2010).

A thunderclap headache evaluation should include head CT and a lumbar puncture if the CT is negative to evaluate for subarachnoid hemorrhage first and foremost. If these studies are unrevealing, many clinicians will then order an MRA or CTA in effort to discover an aneurysm if suspicion remains high, especially within 12 hours of ictus. Some authors have argued that all patients with explosive headache should be evaluated with conventional angiography even when all the other examinations (including MRA) are normal (Linn and Wijdicks 2002; Polmear 2003). However, as noninvasive vascular technology has improved greatly over time, this argument loses some strength (Chen et al 2008; Grayev et al 2009). More recently, a mathematical analysis suggested that a follow-up lumbar puncture is highly cost- effective, but that CTA is questionable in this regard with no clearly defined utility (Malhotra et al 2016).

If no aneurysm is revealed, or if a different etiology is highly suspected based on the presentation, other studies are warranted. When considering cerebral venous thrombosis, CT is often inadequate for diagnosing it, and MRV or CTV is necessary to exclude this disease. When pituitary apoplexy is suspected, dedicated views of the sella turcica should be requested. When reversible cerebral vasoconstriction syndrome is of concern, particularly with recurrent thunderclap headache, serial arterial imaging (be it MRA, CTA, or conventional angiography) may be required to detect it because it can be an intermittent phenomenon that also may not be visible on imaging performed early in the course. When a patient with a thunderclap headache has a completely negative work-up, a diagnosis of primary thunderclap headache may be assigned.

(2) Worsening headache pattern. A worsening headache pattern must be interpreted in the context of a patient's overall headache history. Headaches of recent onset may indicate a mass lesion, such as a brain tumor, abscess, or subdural hematoma. Although mass lesions often present with focal neurologic deficits or papilledema, these features may be absent, particularly if the mass lesion is slow-growing or in a silent area. In this context, neuroimaging is mandatory.

When progression occurs in the context of a well-established primary disorder, 2 possibilities exist. Progression may represent the development of a new headache disorder (either primary or secondary) superimposed on a preexisting primary headache. Alternatively, progression may represent the transformation of a primary preexisting headache disorder. If these possibilities cannot be differentiated clinically, investigation is necessary.

Migraine and tension-type headache are well known to progress. Migraine may evolve to a condition known as chronic migraine, in which headache attacks (not necessarily migraine attacks) occur 15 or more days per month (or 180 or more days per year) with an average duration of 4 or more hours per day. Subjects with chronic migraine usually report a process of transformation over months or years, characterized by increasing headache frequency. Up to 80% of patients seen in specialty headache centers have this condition (Silberstein et al 2008; Evers and Marziniak 2010).

Risk factors for the development of chronic migraine include high frequency of headaches prior to transformation, obesity, stressful life events, alcohol overuse, hypothyroidism, viral infections, head trauma, snoring, and sleep disturbances. Overusing acute medications is the most important risk factor for chronic migraine; it is present in more than 80% of chronic migraine patients in subspecialty clinics (Dodick 2009).

A gradual progression of headache in a migraine sufferer who has readily identified exacerbating factors (medication overuse) and a normal examination is most likely chronic migraine. Patients who have atypical clinical features or exacerbating factors that cannot be easily identified require neuroimaging. Patients who have atypical clinical features or exacerbating factors that cannot be identified easily require further investigation.

(3) Headache with systemic illness or systemic symptoms. Many systemic disorders are associated with a prominent complaint of acute headache, including intracranial and extracranial infections (meningitis, encephalitis, Lyme disease, HIV, sinusitis), hypoxia and hypercapnia (high-altitude illness, diving, sleep apnea), dialysis, uncontrolled arterial hypertension, hypotension, hypothyroidism, fasting, collagen vascular disorder, systemic arteritis, and carbon monoxide poisoning, among others (Gladstone and Bigal 2008).

Clues that the headache is associated with a systemic illness include systemic symptoms, such as fever, neck stiffness, cutaneous rash, fatigue, malaise, and arthralgias. A skin rash could suggest Lyme disease (erythema migrans), herpes zoster (vesicles distributed in a dermatomal pattern), or sarcoidosis (erythema nodosum). Other dermatologic disorders might suggest the presence of a systemic or localized disease, such as antiphospholipid antibody syndrome or Sneddon syndrome (De Luca and Bartleson 2010). A clinician should search for opportunistic infections (including toxoplasmosis and cryptococcal meningitis) and malignancy in patients who have AIDS or HIV risk factors (Gladstone and Bigal 2010).

When patients have cancer, brain and leptomeningeal metastasis should be considered. Depending on the clinical setting, blood work, neuroimaging, and CSF examination may be required.

(4) Headache with focal signs other than typical visual or sensory aura. Aura is most commonly associated with migraine, but also may occur with other primary headaches (chronic paroxysmal hemicrania, cluster headache, and tension-type headache) (Matharu and Goadsby 2001; Peres et al 2002; Krymchantowski 2005; Peres and Vieira 2006; Ekbom et al 2009). Typical migraine aura is rarely associated with secondary causes.

Focal signs other than aura are divided into those that are transient and those that are permanent. Transient focal signs may be the manifestations of seizure, transient ischemic attack, and toxic-metabolic disorders. Permanent deficits (even those that are partial and difficult to detect unequivocally) may be caused by stroke, mass lesion, arteriovenous malformation, or collagen vascular disease. Appropriate workup includes neuroimaging, collagen vascular evaluation, and sometimes lumbar puncture. Differentiating a headache aura from a simple partial seizure may be difficult. Table 3 describes clinical clues that are useful in establishing this differentiation. If seizure is suspected, EEG, followed by neuroimaging (in subjects who have not been previously investigated), is required. Postictal headaches might be of special importance, especially considering that migraine and epilepsy are comorbid (Bigal et al 2003).

Table 3. The Aura in Migraine and Epilepsy Symptom Migraine Epilepsy Duration of aura 15 to 60 minutes Brief, often--shorter than 1 min Automatisms Unusual Frequent for complex partial seizures Gastrointestinal aura Abdominal pain (rare); "Butterflies"--rising epigastric sensation Nausea (common) Visual disturbances Positive or negative Complicated visual phenomenon Paresthesias Common (5 to 60 minutes) Common (seconds to minutes) Altered consciousness Usually responsive Often unresponsive Olfactory Very uncommon More common Aphasia Common Common Déjà vu Rare Common

Modified from: (Bigal et al 2003)

(5) Headache triggered by cough, exertion, or orgasm. The key issue in establishing this red flag is to identify the sudden development of a severe headache temporally related to a trigger. In other words, severe headache unequivocally triggered by cough, heavy exercise, or orgasm must be investigated. Postcoital headaches, mild headaches following exercise, and mild headaches followed by cough do not seem to be associated with secondary headaches at a higher risk than headaches not associated with red flags.

A headache triggered by straining, coughing, or sneezing suggests a hindbrain malformation, occipitocervical junction disorder (including Arnold-Chiari malformation), increased intracranial pressure, or vasospasm. With orgasmic headaches, one must exclude subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, and mass lesions (Wang and Fu 2010).

(6) Headache during pregnancy or postpartum. Most headaches that occur during pregnancy or postpartum are migraine or tension-type headaches. In a pregnant or postpartum woman with a history of migraine or tension-type headache, without atypical features and with a normal examination, investigation is usually not necessary. However, some women report new onset of severe headaches with migraine features, or a worsening pattern of a previously diagnosed primary headache. In these cases, intracranial hypertension or hypotension, cortical vein or cranial sinus thrombosis, carotid dissection, reversible cerebral vasoconstriction syndrome, and pituitary apoplexy enter into the differential diagnosis, especially in the proper clinical context (O'Neal 2017). These disorders are much more common in the third trimester or in the early postpartum period. Stroke is thought to be more common in late pregnancy and the early postpartum period. Neuroimaging, including MRI and MRA, is necessary to exclude such vascular disorders. The differential diagnosis also includes preeclampsia, a multi-system disorder with various forms. In addition to hypertension and proteinuria, tissue edema, thrombocytopenia, and abnormalities in liver function can occur. Preeclampsia appears to involve a strong maternal inflammatory response with broad systemic activity. Subsidiary investigation includes blood and urine testing (Loder et al 2006; Contag et al 2009).

(7) Positional headaches. Orthostatic and reverse-orthostatic headaches bring to mind dysregulation of cerebrospinal fluid pressure or volume. Though orthostatic headaches are typically due to low pressure/volume, and reverse- orthostatic headaches can be due to elevated pressure/volume, the opposite may also be true. In fact, elevated pressure/volume usually does not present with positional headaches, but rather with visual changes, pulsatile tinnitus, and papilledema, with variable but commonly migrainous headache quality (Wall et al 2014). The diagnosis of a low pressure/volume state is suggested not only by orthostatic headache, but also by “second-half-of-the-day headache.” Migraine features are common, and if significant hindbrain descent occurs, cerebellar and brainstem signs and symptoms may be present. MRI with gadolinium may show “brain sag,” pituitary engorgement, and pachymeningeal enhancement, and MRV may show the “venous distention sign” of a convex appearance to the transverse sinuses on sagittal view (Agid et al 2008; Mokri 2013). Some orthostatic headaches are due to slow, undetectable leaks or result from increased compliance of the lower lumbar CSF space without actual leak (Leep Hunderfund and Mokri 2008). Spinal CSF leaks, traditionally difficult to detect, are increasingly recognized as a cause of orthostatic headaches, with some leaks having the etiology of a CSF-venous fistula (Kranz et al 2017). Other orthostatic headaches are not due to CSF pressure dysregulation at all, but rather to autonomic dysfunction in disorders such as orthostatic hypotension and postural orthostatic tachycardia syndrome (Lanier et al 2011). Finally, orthostatic headache may also be reflective of vestibular pathology, particularly in the presence of vertigo, nystagmus, and other positional triggers.

(8) Headache in the elderly. Headache in this age group should always be investigated for secondary cause, although primary headaches do occur. Giant cell arteritis is an underdiagnosed and preventable cause of visual loss in the elderly. When giant cell arteritis is suspected (headache, constitutional signs and symptoms, jaw claudication, temporal artery tenderness, transient neurologic symptoms, etc.) and the erythrocyte sedimentation rate is elevated, empiric treatment with steroids is justified and mandatory while awaiting the results of a biopsy of the temporal artery. The workup must be guided by the clinical picture, but often includes a complete blood cell count with differentiation, sedimentation rate, and chemical profile (Nahas 2012). Headache in the elderly associated with activity may be an anginal equivalent, a rare disorder sometimes termed “cardiac cephalgia” (Bini et al 2009). Other common diagnostic considerations are cervicogenic headache from severe degenerative disease, metastatic cancer, and subdural hemorrhage; these are usually suggested by typical history and examination findings. A common primary headache disorder in the elderly is hypnic headache (see below).

(9) Sinus symptoms and headache. The interplay of sinus symptoms and migraine is a complex relationship and can pose challenges in diagnosis and treatment (Charleston et al 2014). Congestion, rhinorrhea, aural fullness, and facial pain may occur in primary headache disorders (migraine, tension-type, and cluster headaches), often leading to a misdiagnosis of “sinus headaches.” In 1 series, only 5% of suspected sinus headaches actually met criteria for this diagnosis (acute sinus infection with headache that resolves after appropriate antimicrobial therapy), leading to incorrect treatment with antibiotics in a vast majority, sinus endoscopy in about a quarter, and even septoplasty in about 15% (Foroughipour et al 2011). A diagnosis that is not to be missed is sphenoid sinusitis, an elusive entity due to the general lack of obvious sinus symptoms. Fever and facial numbness are 2 key features suggesting the disorder, which are easily seen on neuroimaging. Undiagnosed, it can lead to significant morbidity.

(10) The eye and headache. Most ophthalmologic disorders in which a symptom of headache is common are readily diagnosed based on the obvious abnormal physical manifestations typical of these problems. However, these signs may be absent or easily overlooked, as in acute angle closure glaucoma (Renton and Bastawrous 2011); therefore, one must maintain clinical suspicion in order to arrive at the correct diagnosis. Some other examples of ocular disorders that may not have obvious physical abnormalities are dry eye, keratitis, uveitis, and trochleitis (Friedman et al 2010). Not all headaches accompanied by abnormal physical appearance of the eye are ophthalmologic in nature, of course, with the trigeminal autonomic cephalgias being the best example (see below).

Diagnosing a primary headache disorder

In the absence of secondary headache, the clinician can proceed to diagnosing a primary headache disorder. If the headache is atypical or difficult to classify, the possibility of secondary headache should be reconsidered, although the modifying effect of any treatment should be kept in mind. Discussing the diagnostic criteria of primary headaches is beyond the scope of this article. The objective of this section is to propose a strategy to approach the primary headaches, after excluding secondary disorders.{embed="pagecomponents/media_embed" entry_id="8410"}

If a patient has acute headache and secondary headache syndromes have been excluded, either by clinical history or appropriate investigation, the next step is to assign the primary headache diagnosis. Patients can be divided into those whose headaches are of low-to-moderate frequency (fewer than 15 headache days per month) or those whose headaches are of high frequency (15 or more headache days per month). Based on average duration of a typical untreated headache attack, the headache syndrome is classified as either short-duration (less than 4 hours a day) or long-duration (4 or more hours) (Lipton et al 2004).

Low-to-moderate frequency headaches of long duration"

Low-to-moderate frequency headaches of long duration include episodic migraine and episodic tension-type headache. The main pain features of tension-type headache are bilateral location, non-pulsating quality, mild to moderate intensity, and lack of aggravation by routine physical activity. The pain is not accompanied by nausea or vomiting, although either photophobia or phonophobia (but not both) may occur (Headache Classification Committee of the International Headache Society 2013). Even though episodic tension-type headache is the most prevalent primary headache disorder in the population, it is not a frequent cause of medical visits.

Migraines are the most common acute headaches seen in the emergency department, by far more frequent than secondary headaches (Friedman and Lipton 2011). Migraine attacks in the acute care setting are usually severe, throbbing, and associated with nausea, photophobia, or phonophobia. If the attack is severe, the patient may be prostrate and pale, sometimes vomiting. Although unilaterality of pain is a diagnostic criterion, it may be bilateral. It is not necessary to investigate a typical attack. However, migraine-like attacks not responsive to treatment and requiring prolonged observation (longer than 12 hours) should be investigated.

Presentations other than typical migraine with or without aura are more common in the emergency department than in other settings. Migraine with brainstem aura is a subtype characterized by at least 2 of the following aura symptoms, all fully reversible: dysarthria, vertigo, tinnitus, decreased hearing, double vision, ataxia, and decreased level of consciousness. The headache fulfills criteria for migraine (Headache Classification Committee of the International Headache Society 2013).

Hemiplegic migraine is the first migraine syndrome to be linked to a specific set of genetic polymorphisms (Ducros 2014). This is migraine with aura, except that the aura includes motor weakness (hemiplegia) and may be more prolonged than 60 minutes (up to 24 hours). In familial hemiplegic migraine, at least 1 first-degree relative has had similar attacks (also meeting these criteria). Cerebellar ataxia occurs in 20% of familial hemiplegic migraine sufferers. Headaches that otherwise meet these criteria but present without family history of the disorder are classified as sporadic hemiplegic migraine. Unless patients already have a diagnosis of hemiplegic migraine (and were, therefore, previously investigated), additional investigation is necessary.

Status migrainosus refers to an attack of migraine with a headache phase that lasts longer than 72 hours. The pain and associated symptoms are debilitating, by definition.

Persistent aura without infarction is diagnosed when aura symptoms, otherwise typical of past attacks, persist for more than 1 week, and investigation shows no evidence of infarction. It is an unusual but well-documented complication of migraine that is now included in the International Headache Society classification.

Migrainous infarction is an uncommon occurrence. One or more otherwise typical aura symptoms persist beyond 1 hour, and neuroimaging confirms ischemic infarction. Strictly applied, these criteria distinguish this disorder from other causes of stroke, which must be excluded. The neurologic deficit develops during the course of an apparently typical attack of migraine with aura and exactly mimics the aura of previous attacks (Headache Classification Committee of the International Headache Society 2013).

High-frequency headaches of long duration

High-frequency headaches of long duration include chronic migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Medication overuse is common, being present in more than 80% of chronic migraine patients in subspecialty clinics but in only 30% of chronic headache sufferers in population studies (Silberstein et al 2008; Evers and Marziniak 2010). Patients with chronic migraine seek care when they have a superimposed full-blown migraine (exacerbation). When a clear history is obtained, investigation is not required.

New daily persistent headache is characterized by the abrupt onset of a chronic daily headache. It is classified as a primary headache disorder, although a viral prodrome may precede the onset, suggesting that some syndromes may actually be secondary despite the lack of an obvious demonstrable cause. When patients with acute headache first seek care with this syndrome, thorough investigation is necessary to exclude secondary disorders (Rozen 2014).

Hemicrania continua is commonly mistaken for chronic migraine. Both disorders are characterized by chronic unilateral pain with superimposed painful exacerbations. In hemicrania continua, the exacerbations often are associated with ipsilateral autonomic features, such as conjunctival injection, lacrimation, and ptosis. In chronic migraine, exacerbations are more typically accompanied by nausea, photophobia, and phonophobia. In addition, patients with hemicrania continua usually do not have an antecedent history of episodic migraine. Chronic migraine attacks increase in frequency over time. If the headaches are longstanding, the patient may not remember how they began. Though pain fluctuates in hemicrania continua, it does not usually have the morning and end-of-dosing-interval pattern of exacerbations typical of chronic migraine. It is advisable to offer patients with unilateral chronic daily headache a therapeutic trial with indomethacin (doses of up to 225 mg/day for 3 to 4 days) prior to other intervention (Charlson and Robbins 2014).

Headaches of shorter duration

High-frequency, short-duration headaches include the trigeminal autonomic cephalgias (episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania), SUNCT (short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and SUNA (short lasting unilateral neuralgiform headaches with autonomic features) syndromes, hypnic headache, and exertional headaches.

The trigeminal autonomic cephalgias (TACs) are characterized by unilateral pain in the trigeminal distribution, with ipsilateral autonomic features. The most common disorder in this family is cluster headache. The pain of cluster headache is described variously as sharp, boring, drilling, knife-like, piercing, or stabbing, in contrast to the pulsating pain of migraine. It usually peaks in 10 to 15 minutes but remains excruciatingly intense for an average of 1 hour within a duration range of 15 to 180 minutes. During this pain, patients find it difficult to lie still, often exhibiting marked agitation and restlessness, and autonomic features are usually obvious. After an attack, the patient remains exhausted for some time (Halker et al 2010).

Like cluster headache, the paroxysmal hemicranias are characterized by unilateral attacks of trigeminal pain and autonomic features. In contrast to cluster headache, the paroxysmal hemicranias have 3 main features: (1) greater frequency (more than 5 per day); (2) short lasting duration (2 to 30 minutes); (3) absolute response to therapeutic doses of indomethacin. They are rare (Goadsby et al 2010).

Another trigeminal autonomic cephalgias, SUNCT, is a rare primary headache. The diagnostic criteria require at least 20 high-frequency attacks (3 to 200 per day) of unilateral orbital, supraorbital, or temporal stabbing or pulsating pain, lasting 5 to 240 seconds and accompanied by ipsilateral conjunctival injection and lacrimation. The attacks are characteristically dramatic, with moderately severe pain, peaking in intensity within 3 seconds, and prominent tearing (Goadsby et al 2010).

SUNA syndrome is similar to SUNCT, but it is even rarer. Attacks may last slightly longer and be less frequent. Either conjunctival injection or tearing may be present, but not both, and other autonomic features are more common (Cohen et al 2006). SUNCT and SUNA currently are classified together as 1 syndromic disorder with variation among patients (Headache Classification Committee of the International Headache Society 2013).

Hypnic headache is a primary headache disorder of the elderly, characterized by short-lived attacks (typically 30 minutes) of nocturnal head pain that awaken the patient at a consistent time each night, in many cases on more nights than not. It does not occur outside sleep. Hypnic headache is usually bilateral (although unilaterality does not exclude the diagnosis) and typically mild to moderate, different from the unilateral orbital or periorbital, knife-like, intense pain of cluster headache. Autonomic features are absent (Obermann and Holle 2010).

Headaches triggered by cough, exertion, and sexual activity include the disorders named for these triggers. Especially in patients presenting in the emergency department, or during an attack, these headaches may only be diagnosed after an exhaustive and methodic search for secondary causes. However, in a patient previously investigated or previously diagnosed, repeating the investigation is usually not necessary, and patients should be treated (Wang and Fu 2010).

Conclusions

As previously discussed, the differential diagnosis of the acute headaches requires a systematic approach. In a 1990 review article, John Edmeads stated that even when a patient is quiet and calm, able and willing to present an orderly history, and easy to examine, the headache diagnosis may be difficult (Edmeads 1990). However, during an attack, headache sufferers may not be completely cooperative, and, consequently, the quality of the information may be affected. We have herein presented an orderly approach to differential diagnosis. The precise criteria for each disorder are presented elsewhere (Headache Classification Committee of the International Headache Society 2013). These algorithms should help neurologists move forward quickly and safely when assessing patients with acute headaches. References cited

Agid R, Shelef I, Scott JN, Farb RI. Imaging of the intracranial venous system. Neurologist 2008;14(1):12-22. PMID 18195652

Bigal ME, Lipton RB, Cohen J, Silberstein SD. Epilepsy and migraine. Epilepsy Behav 2003;4(Suppl 2):13-24. PMID 14527480

Bini A, Evangelista A, Castellini P, et al. Cardiac cephalgia. J Headache Pain 2009;10(1):3-9. PMID 19139804

Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med 2007;146(1):34-44. PMID 17200220

Charlson RW, Robbins MS. Hemicrania continua. Curr Neurol Neurosci Rep 2014;14(3):436. PMID 24452694

Charleston L, Strabbing R, Cooper W. Is sinus disease the cause of my headaches? An update on sinus disease and headache. Curr Pain Headache Rep 2014;18(6):418. PMID 24760488

Chen W, Yang Y, Xing W, Qiu J, Peng Y. Sixteen-row multislice computed tomography angiography in the diagnosis and characterization of intracranial aneurysms: comparison with conventional angiography and intraoperative findings. J Neurosurg 2008;108(6):1184-91. PMID 18518726

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. Brain 2006;129(Pt 10):2746-60. PMID 16905753

Contag SA, Mertz HL, Bushnell CD. Migraine during pregnancy: is it more than a headache. Nat Rev Neurol 2009;5(8):449-56. PMID 19597515

De Luca GC, Bartleson JD. When and how to investigate the patient with headache. Semin Neurol 2010;30(2):131-44. PMID 20352583

Dodick DW. Review of comorbidities and risk factors for the development of migraine complications (infarct and chronic migraine). Cephalalgia 2009;29 Suppl 3:7-14. PMID 20017749

Ducros A. Familial hemiplegic migraine: A model for the genetic studies of migraine. Cephalalgia. 2014;34(13):1035-7. PMID 24707017

Edmeads J. Challenges in the diagnosis of acute headache. Headache 1990;30(Suppl 2):537-40. PMID 2272821

Ekbom K, Waldenlind E, Tfelt-Hansen P. Cluster headache and aura. Headache 2009;49(5):786-7. PMID 19456891

Evers S, Marziniak M. Clinical features, pathophysiology, and treatment of medication-overuse headache. Lancet Neurol 2010;9(4):391-401. PMID 20298963

Foroughipour M, Sharifian SM, Shoeibi A, Ebdali Barabad N, Bakhshaee M. Causes of headache in patients with a primary diagnosis of sinus headache. Eur Arch Otorhinolaryngol 2011;268(11):1593-6. PMID 21626445

Friedman BW, Lipton RB. Headache in the emergency department. Curr Pain Headache Rep 2011;15(4):302-7. PMID 21400252

Friedman DI, Gordon LK, Quiros PA. Headache attributable to disorders of the eye. Curr Pain Headache Rep 2010;14(1):62-72. PMID 20425216

Gladstone J, Bigal ME. Headaches attributable to infectious diseases. Curr Pain Headache Rep 2010;14(4):299-308. PMID 20499213

Gladstone JP, Bigal ME. Infectious, toxic, and metabolic headaches. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolff's Headache and Other Head Pain. New York: Oxford University Press, 2008:247-82. Goadsby PJ, Cittadini E, Cohen AS. Trigeminal autonomic cephalalgias: paroxysmal hemicrania, SUNCT/SUNA, and hemicrania continua. Semin Neurol 2010;30(2):186-91. PMID 20352588

Goldstein JN, Camargo CA Jr, Pelletier AJ, Edlow JA. Headache in United States emergency departments: demographics, work-up and frequency of pathological diagnoses. Cephalalgia 2006;26(6):684-90. PMID 16686907

Grayev A, Shimakawa A, Cousins J, Turski P, Brittain J, Reeder S. Improved time-of-flight magnetic resonance angiography with IDEAL water-fat separation. J Magn Reson Imaging 2009;29(6):1367-74. PMID 19472410

Halker R, Vargas B, Dodick DW. Cluster headache: diagnosis and treatment. Semin Neurol 2010;30(2):175-85. PMID 20352587

Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8(Suppl 7):1-96. PMID 3048700

Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders. Cephalalgia 2004;24:1-160.

Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013;33(9):629-808.

Ju YE, Schwedt TJ. Abrupt-onset severe headaches. Semin Neurol 2010;30(2):192-200. PMID 20352589

Kranz PG, Malinzak MD, Amrhein TJ, Gray L. Update on the diagnosis and treatment of spontaneous intracranial hypotension. Curr Pain Headache Rep 2017;21(8):37. PMID 28755201

Krymchantowski AV. Aura with non-migraine headache. Curr Pain Headache Rep 2005;9(4):264-7. PMID 16004842

Lanier JB, Mote MB, Clay EC. Evaluation and management of orthostatic hypotension. Am Fam Physician 2011;84(5):527-36. PMID 21888303

Leep Hunderfund AN, Mokri B. Orthostatic headache without CSF leak. Neurology 2008;71(23):1902-6. PMID 19047563

Linn FH, Wijdicks EF. Causes and management of thunderclap headache: a comprehensive review. The Neurologist 2002;8:279-89. PMID 12803675

Lipton RB, Bigal ME, Steiner TJ, Silberstein SD, Olesen J. Classification of primary headaches. Neurology. Neurology 2004;63(3):427-35. PMID 15304572

Lipton RB, Silberstein SD, Dodick DW. Overview, diagnosis and classification. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolff's Headache and Other Facial Pain. New York: Oxford University Press, 2008:6-26.

Loder E, Golub J, Rizzoli P, Anger J. Postpartum headache: Avoiding diagnostic and therapeutic pitfalls. Headache and Pain: Diagnostic Challenges. Current Therapy. 2006;17(4):155-65.

Malhotra A, Wu X, Kalra VB, Schindler J, Forman HP. Cost-effectiveness analysis of follow-up strategies for thunderclap headache patients with negative noncontrast CT. Acad Emerg Med 2016;23(3):243-50. PMID 26728524

Matharu MJ, Goadsby PJ. Post-traumatic chronic paroxysmal hemicrania (CPH) with aura. Neurology 2001;56:273-5. PMID 11160973

Mokri B. Spontaneous low pressure, low CSF volume headaches: spontaneous CSF leaks. Headache 2013;53(7):1034- 53. PMID 23808630

Nahas SJ. Headache and temporal arteritis: when to suspect and how to manage. Curr Pain Headache Rep 2012;16(4):371-8. PMID 22552735

Obermann M, Holle D. Hypnic headache. Expert Rev Neurother 2010;10(9):1391-7. PMID 20839413

O'Neal MA. Headaches complicating pregnancy and the postpartum period. Pract Neurol 2017;17(3):191-202. PMID 28473606

Peres MF, Vieira DS. Tension-type headache with aura. Cephalalgia 2006;26(3):349-50. PMID 16472346

Peres MF, Siow HC, Rozen TD. Hemicrania continua with aura. Cephalalgia 2002;22:246-8. PMID 12047466

Perry JJ, Stiell IG, Sivilotti ML, et al. High risk clinical characteristics for subarachnoid haemorrhage in patients with acute headache: prospective cohort study. BMJ 2010;341:c5204. PMID 21030443

Perry JJ, Stiell IG, Sivilotti ML, et al. Clinical decision rules to rule out subarachnoid hemorrhage for acute headache. JAMA 2013;310(12):1248-55. PMID 24065011

Polmear A. Sentinel headaches in aneurysmal subarachnoid haemorrhage: what is the true incidence. A systematic review. Cephalalgia 2003;23(10):935-41. PMID 14984225

Renton BJ, Bastawrous A. Acute angle closure glaucoma (AACG): an important differential diagnosis for acute severe headache. Acute Medicine 2011;10(2):77-8. PMID 22041605

Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol 2010;30(2):107-19. PMID 20352581

Rozen TD. New daily persistent headache: an update. Curr Pain Headache Rep 2014;18(7):431. PMID 24820732

Sheikh HU, Mathew PG. Reversible cerebral vasoconstriction syndrome: updates and new perspectives. Curr Pain Headache Rep 2014;18(5):414. PMID 20425213

Silberstein SD, Lipton RB, Saper JR. Chronic daily headache, including transformed migraine, chronic tension-type headache, and medication overuse headache. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolff's Headache and Other Head Pain. New York: Oxford University Press, 2008:247-82.

Wall M, Kupersmith MJ, Kieburtz KD, et al. The idiopathic intracranial hypertension treatment trial clinical profile at baseline. JAMA Neurology 2014;71(6):693-701. PMID 24756302

Wang SJ, Fuh JL. The “other” headaches: primary cough, exertion, sex, and primary stabbing headaches. Curr Pain Headache Rep 2010;14(1):41-6. PMID 20425213

**References especially recommended by the author or editor for general reading.

Former authors

Richard B Lipton MD, Benjamin W Friedman MD (original authors), and Marcelo E Bigal MD PhD

Differential diagnosis list

Abscess aneurysmal subarachnoid hemorrhage antiphospholipid antibody syndrome Arnold-Chiari malformation arterial dissection (intra- and extracranial) arteriovenous malformation brain and leptomeningeal metastasis brain tumor carbon monoxide poisoning carotid dissection cerebral venous (or sinus) thrombosis CNS angiitis collagen vascular disorder colloid cysts of the third ventricle cortical vein or cranial sinus thrombosis cryptococcal meningitis CSF hypotension and acute sinusitis (particularly with barotrauma) dialysis encephalitis fasting giant cell arteritis herpes zoster (vesicles distributed in a dermatomal pattern) hindbrain malformation HIV/AIDS hypotension hypothyroidism hypoxia and hypercapnia (high-altitude illness, diving, sleep apnea) increased intracranial pressure intracerebral hemorrhage Lyme disease mass lesion meningitis meningoencephalitis occipitocervical junction disorder pituitary apoplexy pre-eclampsia reversible benign CNS angiopathy sarcoidosis (erythema nodosum) seizure sinusitis Sneddon syndrome stroke subdural hematoma systemic arteritis toxic-metabolic disorders toxoplasmosis transient ischemic attack uncontrolled arterial hypertension