INTRODUCTION
Headache is a very common complaint. Approximately 90% or more of the general population report a lifetime history of headache.1 It has been estimated that 1-year prevalence of headache in Karnataka state of India is 64%.2 Hence, it is commonly encountered in routine clinical practice. People seek medical attention when their headaches become recurrent and disabling or present as an acute catastrophic event. It becomes challenging for the physicians to make sense of headache as a complaint and arrive at a diagnosis. The causes of headache are many and until and unless these patients are evaluated with a systematic and structured approach, the underlying conditions may remain elusive. Hence, in the following sections, the principles of approach to a headache patient are discussed from a practical framework.
OBJECTIVES OF HEADACHE EVALUATION
As stated earlier, the approach to a headache patient may be challenging because there are more than 300 causes to consider which may overwhelm the logical thinking process. It is always better to start with five basic questions. These are:
- Is it a sinister headache? (Is it a potentially life-threatening headache? If yes, what will be my immediate action plan?)
- Is it a primary headache? (Have I ruled out common secondary causes?)
- If yes, what is the type of primary headache? (Do the headache features fulfill the clinical criteria of one of the primary headaches?)
- What subtype is it? (Episodic, frequent, infrequent, chronic, complicated)
- What is its impact on patient's life? (Especially in frequent and chronic headache patients)
GENERAL POINTS ABOUT RULING OUT A SECONDARY HEADACHE
When a headache patient visits a physician for the first time, one of the chief concerns is not to miss a secondary cause of headache. The International Classification of Headache Disorders, 3rd edition (beta version) (ICHD-3β) also classifies headache disorders into two groups, namely:
- Primary headaches
- Secondary headaches.
Further, at the end of defining criteria of each primary group in ICHD-3β, it is mandated that all possible secondary causes need to be ruled out.3 There are no biological markers for primary headaches. To make the matters worse, primary headaches are much more common than secondary headaches. Therefore, in the clinic, the physician has to look for secondary headaches (which are uncommon) from a large group of patients with primary headaches (which are common). Thus, it becomes challenging to make sure that one is not missing a hidden secondary cause when one is diagnosing a primary headache. However, since headache is such a common problem, it is neither possible nor cost-effective to screen all patients of headache with imaging or other investigations. Hence, certain clinical red flags have been identified which if present suggest the possibility of secondary headaches. Patients with red flags should be subjected to investigations. Physicians dealing with headache patients must therefore be familiar with these red flags. Red flags may be remembered by a mnemonic (for example, SNOOP4 given by Professor David Dodick).4 Other way is to remember three key elements in headache diagnosis namely onset and progression, certain headache characteristics, and headache associations (OCA, Table 1). Certain historical features can be reassuring for the diagnosis of a primary headache. These include onset in adolescence and early adulthood, a stable phenotype over a long period of time, positive family history of a primary headache (like migraine), strong association with menstruation, and side shifting headaches (in case of migraine).4
PRACTICAL FRAMEWORK OF THE APPROACH TO A HEADACHE PATIENT
It is important to know how to frame your questions to get your diagnosis. Headache patients may present to the emergency department (ED) or in the outpatient clinic. The approaches are slightly different and hence discussed separately.
Patient Presenting in Emergency Department
When did this headache start? Did you have previous history of such headaches? These are the first questions to be asked. If the patient says that she had similar episodes of such headaches in the past, possibility of an acute attack of a primary headaches exits and needs to be characterized further. It may be possible that even this particular attack may be of secondary cause. Hence, questions regarding red flags need to be asked even if there is previous history of primary headaches. All patients with a thunderclap headache (TCH) presentation, that is, sudden onset headache reaching maximal intensity instantaneously must be evaluated for a secondary cause (Box 1). Up to 25% will turn out to be subarachnoid hemorrhage. Any first attack of worst headache ever, even though not fulfilling TCH criteria (that is, attaining maximum intensity within 1 min), must also be evaluated for a secondary cause. Additionally, history of fever, generalized malaise and weight loss, seizures, jaw claudication, recent exposure to toxins or drugs, recent head trauma, substance abuse or its withdrawal, history of symptoms related neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cervical structure must be taken. Sometimes, myocardial ischemia can present as acute severe headaches. History of previous exertion headaches in an elderly or ischemic heart disease may be useful.
5Occasionally, psychiatric patients present with acute headaches in ED. However, headaches attributable to a psychiatric disorder should only be considered after exclusion of other causes.
Certain points in general and systemic examination are important to note. Vital parameters should be assessed for elevated blood pressure, pulse rate, and temperature. An elevated blood pressure is often the result and not the causative factor of severe headache. However, if blood pressure is more than 180/120 mmHg, possibility of hypertensive crisis with or without encephalopathy must be entertained. Conditions like intracranial hemorrhage, infarction, subarachnoid hemorrhage, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome (RCVS) may be entertained. Uncommon causes for hypertension-related headaches include pheochromocytoma and autonomic dysreflexia in patients with spinal cord injury. General physical examination should include skin (for rash), head, and neck (for sinus tenderness, conjunctival injection, temporal artery tenderness, bruit, and enlarged lymph nodes).
Patients presenting in ED with headache and focal or global neurological deficits will invariably have a secondary cause. Hence, it is relatively easy to provisionally diagnose these patients as secondary headache and go ahead with appropriate investigations. For example, an acute headache presenting with focal deficit like hemiplegia in an uncontrolled hypertensive patient may suggest a diagnosis of intracranial hemorrhage and an urgent plain computed tomography scan of cranium will clinch the diagnosis. However, the signs may be subtle during the initial phase of a disease and hence, may be missed. For example, a patient presenting with acute onset hemicranial headache and neck pain may not have much clinical signs except subtle painful Horner's syndrome and hence, the diagnosis of carotid dissection might be totally missed. Essentially, the clinical challenge lies in detection of soft signs. Any subtle deficits on examination assume importance to correctly proceed toward a diagnosis of secondary headache.
Patient Presenting in Clinic
For patients presenting in the clinic, the evaluation should proceed in a systematic manner as follows:
Onset and Temporal Course
Headache onset and course provides very important clues for headache diagnosis. Based on this, headaches can be broadly classified into three groups, namely
- Acute new onset headaches
- Episodic recurrent headaches
- Chronic headaches.
Acute new onset headaches such as TCH have been discussed in the previous section. Primary headaches with acute de novo onset may also occur but difficult to diagnose unless secondary causes are ruled out. Most of the primary headaches begin insidiously and follow a pattern of recurrence with ups and downs in frequency. Three common primary headaches are tension-type headache (TTH), migraine, and cluster headache (CH) (Table 2). Tension-type headache is a relatively featureless headache with patients complaining headaches (or heaviness), usually mild, dull, and pressing type, usually holocranial with absence of systemic features like nausea and/or vomiting, photophobia, and phonophobia. Patients do not have motion sensitivity and, therefore, can move around and work despite the headache. The duration varies widely from 30 minutes to 7 days. Most of them do not present to the clinic. In contrast, chronic TTH (CTTH) patients may present to the clinic. Typically, CTTH patients have long history of daily or near daily headaches and are poorly responsive to treatments. Despite this, most of them are able to carry out their day-to-day work. Many of these patients have psychiatric comorbidities and some have pericranial tenderness.
The most common headache seen in the clinic is migraine. Migraine patients have recurrent, episodic, long-lasting hemicranial or holocranial headaches, throbbing or bursting in character, usually moderate to severe in intensity that inhibits or prohibits work, builds up slowly and abates slowly, some preceded by aura and associated with nausea and/or vomiting, photophobia, phonophobia, and motion sensitivity (aggravation of headache due to movements and hence preference to lie down quietly). Onset is usually in adolescence or early young age. A common reason for presentation in the clinic is worsening over past few months to years. The clinician should try to analyze the reasons for the worsening. The usual causes include stress, family conflicts, bereavement in the family, change in job, and study pressures. Triggers strongly influence the occurrence of migraine attacks. Sometimes, the attacks become frequent especially due to persistence of triggers like stress or sleep deprivation. In up to 3% of the patients, episodic migraine headaches can transform into a chronic state leading to chronic migraine. Many such chronic migraine patients abuse acute pain medications such as analgesics, triptans, ergots or opioids, and thus also have medication overuse headache (MOH). ICHD-3β allows both the diagnoses in such patients.3 To diagnose MOH, information about the duration, nature, and frequency of drug(s) abused is important. Chronic migraine patients may lack typical characteristics of migraine in many of their attack days and the headaches may have the phenotype of TTH.
6
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
However, when asked in detail, at least some days still retain the migraine phenotypic features. ICHD-3β requires presence of at least 8 such days to make chronic migraine diagnosis.3 Certain risk factors for chronification have been identified. These need to be identified as some of them are modifiable (Table 3).5 Chronic migraine along with CTTH are the two common forms of long duration primary chronic daily headaches. The other two, namely, new daily persistent headache and hemicrania continua (HC) are uncommon. The differential features are tabulated in Table 4.
The third common type of headache seen in clinic is CH, the first disorder grouped under trigeminal autonomic cephalalgias (TACs). Cluster headache has short-lasting side-locked unilateral severe headaches with prominent ipsilateral cranial autonomic symptoms/signs (CAS) and restlessness. The headaches usually peak early within minutes and abate abruptly as they had begun. In typical cases, the phenotype is distinct. Acute onset with episodic 1–8/day short duration attacks with circadian periodicity suggests the diagnosis. History of clustering of such attacks around weeks/months clinches the diagnosis. Chronic subtype with daily attacks without remission is uncommon. In contrast, the other headache in this group, namely, paroxysmal hemicrania (PH) with similar clinical features occurs more commonly in chronic form and is distinguished from cluster by the brevity of attack duration and greater number of attacks per day.7
| |||||||||||||
Headache Characteristics
Attack duration
An important key feature in headache diagnosis is based on duration of an individual attack. The ICHD-3β differentiates primary headaches based on attack duration3 and these have been broadly divided into two groups, namely:
- Long duration headaches
- Short duration headaches.
Migraine headaches are long duration headaches (4–72 hours), whereas TACs are short duration headaches lasting for minutes to 3 hours. There are headaches which can last from seconds to few minutes, examples being short-lasting unilateral neuralgiform headache attacks (SUNHA), trigeminal neuralgia (TN), and stabbing headaches. Although, in clinical practice, some overlaps are common, if most of the headache episodes have attack duration within a defined category, it becomes much easier to narrow down the differentials. In chronic headaches, the number of attack days should be noted along with the duration of exacerbations, if any.
Attack Frequency
Based on attack frequency, headaches are classified into two groups:
- Episodic (low or medium frequency headaches occurring less than 15 days in a month)
- High frequency (headaches occurring more than 15 days in a month).
Although arbitrary, this distinction is useful as it leads to different differentials. Together with information about attack duration, it can lead to a practical diagnostic algorithm for primary headaches (Flowchart 1).6 For all primary headaches, ICHD-3β requires presence of certain minimum number of attacks for the diagnosis. It is important to note that attack frequency is also important to categorize headaches as episodic or chronic. Also, subtyping of the TACs group is based on number of attacks per day.3 As one move from CH to PH and SUNHA, the duration becomes less and less but the attack frequency/day becomes more and more (see the chapter on Trigeminal Autonomic Cephalalgias).
Time to Peak
While there is usually a slow build up in migraine, CH and PH have a very rapid peaking within minutes. Tension-type headache patients usually have more or less same intensity of headache with occasional increase especially during evening hours after work. Information about time to peak has a bearing on treatment as well. For example, some migraine patients may have rapid peaking; if present, such patients should be advised a rapidly acting triptan such as subcutaneous sumatriptan to abort their attacks.
Time of the Day
In general, headaches can occur at any time. Some headaches have predilections for nocturnal occurrence. Classic examples include hypnic headache (HH) and CH. In HH, attacks tend to occur every time at a same time of the night (usually 2–3 hours after the onset of sleep) and hence, the name “alarm clock headaches”. In CH, the attacks may also be fixed at particular times of the day or night. Daytime naps are known triggers for CH. Early morning headaches are seen in secondary headaches due to raised intracranial pressure (ICP) and headaches secondary to sleep apnea. Some migraine patients can also complain of headaches upon awakening.
Time of the Year
Cluster headache may display circumannual periodicity in addition to circadian periodicity. The cluster periods lasting for weeks to months tend to occur in certain months/seasons of the year. Occasionally, migraine patients may also show cyclical patterns (cyclical migraine).8
Location and Laterality
Location of pain may provide useful clues. Trigeminal autonomic cephalalgias are usually unilateral and side-locked pain predominantly affecting V1 distribution. Characteristically, the maximum pain intensity occurs in and around the eye. In 15% patients, the headaches change sides, either within (rarely) or between the cluster periods. Most of the patients complain the pain maximally at orbital, retro-orbital, and periorbital areas. Migraine headaches can be hemicranial or holocranial. In many, hemicranial headaches may progress to involve the entire head. However, more importantly, even in those with hemicranial headaches, side changes from bout to bout. Side-locked migraine occurs in around 15–20% of patients and is a relative red flag. Tension-type headaches are usually band-like and bilateral. In neuralgias, the pain usually radiates to another region depending upon the distribution of the nerve. For example, in TN, the pain primarily involves V2, V3, and V1 distribution. Isolated V1 distribution of pain in TN occurs rarely and alternate diagnosis such as SUNHA may be considered. Pain and tenderness along temporal artery may suggest temporal arteritis. Headache due to raised intracranial tension usually occurs in bifrontal and bioccipital areas.
Pain Character
This is the most difficult part in evaluation as people use different expressions to describe the character of their pain. Some cannot describe them at all and insist only on severity. Migraine pain is usually described as throbbing or bursting, whereas TTH pain is described as heaviness, pressing, or band-like. Trigeminal autonomic 9cephalalgias patients describe the pain as boring, piercing, electric current-like, burning or bursting. It is noteworthy that because of these variable expressions, ICHD-3β has not defined any character of pain in TACs in contrast to migraine and TTH.
Severity
Although occurrence of recurrent severe pain brings the patient to the doctor, in terms of differential diagnosis, assessment of headache severity is not very useful. Tension-type headache is usually described as mild whereas migraine patients have moderate to severe and TAC patients have extremely severe headaches. However, these complaints may vary widely between the groups and also from attack to attack. However, assessment of severity is important for stratification of patients in migraine to select the right options of abortive medications. Severity is also important to define the TCH in ED. Change in headache severity has also been taken as an outcome parameter to study the efficacy of a drug.
Associated Symptoms and Signs
Most often, headache history revolves around headache phase. But it is also important to know what happens before and after the headache phase. Hence, these are described separately.
Before the Headache
Many migraine patients have premonitory symptoms before the onset of a clinical attack. These are important to ask because it has been found that 72% patients correctly predicted migraine onset from their premonitory symptoms when evaluated by a prospective electronic-based diary.7 Three most common premonitory symptoms are feeling tired and weary, having difficulty in concentrating, and stiff neck. About 20–25% patients report transient focal neurological deficits in the form of aura in migraine.8 Aura has been less commonly reported from Indian subcontinent. Visual aura is the most common followed by sensory and language aura. Patients with hemiplegic migraine, a rare disorder, may have motor aura. Aura has also been described in CH. Clinically, visual aura in migraine is characterized by four features, namely:
- Slow evolution and lasting over 20–30 minutes
- Occurrence in hemifield distribution
- Positive phenomenon (like scintillations and fortification spectra) followed by enlarging negative phenomenon (like scotomas)
- Disappearance of the symptoms in the same order as that of beginning.
Close differentials include epilepsy in children and young adults and transient ischemic attack in elderly. In retinal migraine, a rare condition, the patients complain of visual loss in monocular distribution.
During the Headache
Three questions regarding associated symptoms and signs are important to ask during the headache phase:
- Systemic complaints: Important symptoms during the headache phase are presence of photophobia, phonophobia, osmophobia, nausea, and vomiting. These should be routinely asked. Among these, nausea and phonophobia are the most common complaints in migraine. It should be noted that all these symptoms may not be preset in all the attacks. Secondly, although classically seen in migraine, these may also be seen in TACs, although in lesser frequency and in much less florid manifestations. Notably, when present in TACs, they are commonly reported lateralized to symptomatic side in contrast to migraine where they are usually bilateral. Tension-type headache patients usually do not report such systemic complaints and hence their headaches are often “featureless”.
- Behavior during the attack: Migraine patients have motion sensitivity. Routine physical activities increase their headaches. Hence, they prefer to limit their movements by lying down or resting in a dark quiet room (to avoid photo- and phonophobia). However, these manifestations depend on severity of the attack, social context, and environment. In contrast to migraine, TAC patients have both motor and behavioral restless during the headache. They usually cannot sit still and tend to perform various activities like pacing around, running, pressing their head repetitively, banging their head, immersing their face in hot or cold water, crying, and shouting. This characteristic feature of “restlessness” has now been included as a diagnostic feature of CH in ICHD-3β.3
- Cranial autonomic symptoms and signs: Ipsilateral cranial autonomic symptoms and signs are the hallmarks of TACs. These include seven features, namely:
- Conjunctival injection and/or lacrimation
- Eyelid edema
- Forehead and facial sweating
- Nasal congestion and/or rhinorrhea
- Sensation of fullness in the ear
- Forehead and facial flushing
- Miosis and/or ptosis.
Presence or absence of these symptoms must be asked routinely to all headache patients. It is important to note that aural fullness has been recently included as a CAS in ICHD-3β.3 Presence of even a single CAS can be taken as a diagnostic criterion in TACs. Some of these features may also occur bilaterally in TACs despite the headache occurring unilaterally; however, bilateral CASs are more common in migraine and can be seen in up to 50% of patients.910
|
After the Headache
Many migraine patients complain of fatigue and lack of concentration even after their headaches are over. This may persist for hours and has been called as postdrome. In contrast, TAC patients are usually free of postdrome; their attacks begin abruptly and end abruptly. While episodic TTH patients are usually free of any symptoms once the headaches are over, CTTH patients usually complaint an all-pervasive heaviness for most of the days.
Triggers
Migraine gets precipitated by well-known triggers and it is important to ask them. They aid in diagnosis. Triggers, if avoided, can lead to significant decrease in the frequency of headache episodes; however, not all can be avoided. Some patients are well aware of their triggers and try to avoid them before they seek consultation. Some, however, are oblivious of the “concept” of triggers. Once identified by them, they can be instructed to avoid at least some of them and thus avoid the precipitation of headaches. Common triggers in three common primary headaches are shown in Table 5.
Besides these three primary headaches, there are a group of uncommon primary headaches wherein many entities are characterized and defined by their association with a precipitating factor. Examples include cough (Valsalva maneuver)-induced headaches, exercise-induced headaches, and headaches associated with sexual activity. It is important to note that similar presentations can also be seen in secondary etiologies. Other headaches in this group are described by assuming cause and effect relationship. Examples are cold stimulus headache and external pressure headache. It is also important to ask for effect of posture on headaches. Characteristically, low cerebrospinal fluid pressure headaches are promptly relieved while lying down from a sitting or standing posture. Many neuralgias and SUNHA get precipitated by cutaneous as well as activity-related triggers like talking, eating, shaving, and drinking. Characteristically, an innocuous touch or contact with strong breeze on the affected side can precipitate neuralgic pains.
Family History
Migraine patients have a strong family history of headaches. It is important to know because it aids in diagnosis especially in children and in others where all the defined criteria are not met. Cluster headache patients also have higher occurrence of headaches including CH in their family although the effect size seems to be small.
Drug History
It is very important to take drug history in primary headaches. Previous or current intake of acute and preventive medications and their efficacy are important to note. Needless to re-emphasize the fact that presence of MOH should be actively sought in chronic headaches. Response to indomethacin in adequate doses is considered as a diagnostic criterion in PH and HC. Many drugs can trigger TCHs due to RCVS such as cocaine, amphetamines, sildenafil, marijuana or marihuana, and triptans. Hence, history of such drug intake should be sought in patients suspected of RCVS. History of substances abuse and/or their withdrawal should also be taken as some secondary headaches may be caused by them (Table 6).11
| |||||||||||||||||||||||
Comorbidities
Psychiatric
Psychiatric comorbidities such as anxiety, depression, mania, and somatization are common in headache patients. It is important to ask and characterize them as until and unless these are addressed, treating headaches alone may not be rewarding. Presence of these associated conditions may provide therapeutic opportunities in choosing a preventive medication while at times may result in limitations. For example, amitriptyline may be a good choice in patients of migraine with depression.
Systemic
Many somatic conditions are comorbid with migraine. Examples include bronchial asthma, atopy, and hypertension. History should incorporate such associations because these may provide both therapeutic opportunities as well as limitations when both acute and preventive medications are considered. A common example is contraindication of β-blockers like propranolol in migraine patients with bronchial asthma.
Personal History
Migraine is common in young women of childbearing age. Hence, history must include details of menstruation, pregnancy, and use of contraceptives. Female migraine patients (with aura) who smoke and use contraceptives are at higher risk of future vascular events.10 They need to be counseled accordingly. Many CH patients are smokers. Many have precipitation of cluster attacks during the cluster period with modest intake of alcohol. Some patients already recognize this fact and abstain during their cluster period; others need to be made aware. Repeated attacks of TCHs during sexual activity are most commonly due to RCVS. Such patients should refrain from using vasoactive drugs listed above.
Examination
Primary headache patients have normal neurological examination. The exception being presence of Horner's in patients with CH even after the attack during the cluster period. In some uncommon migraine subtypes, patients may develop prolonged neurological deficits. At the minimum, measurement of blood pressure, detailed optic nerve functions including fundus examination and field testing by confrontation and elicitation of subtle neurological deficits in other cranial nerves, motor, sensory, and cerebellar systems are a must in all headache patients. Pituitary tumors are notorious for escaping clinical detection as they may cause very subtle deficits initially. They can mimic migraine, tension, and CH like headaches.11
Diagnostic Formulation
After detailed history and examination, a diagnostic formulation must be made. Sometimes, diagnosis may 12remain provisional till certain investigations are done. However, attempts should be made to distinguish between primary and secondary headaches and answer the first four questions listed at the beginning of this chapter. It is to be noted that a patient may be having more than one type of headaches at a given time or may have past history of different types of headache. However, many patients may not be aware of this. Careful history will unravel the multiple headache types and each must be approached separately in the same sequential and structured manner. The treatment may be directed toward the dominant type.
Investigations
After detailed history and examination, most of the patients have clear cut features of a primary or secondary headache. Those with red flags or atypicality must be investigated. Guidelines and consensus statements of how to investigate a headache patient have been published.12 However, physicians must decide on case-to-case basis.
Role of Headache Diary
Headache diary is an important tool to follow-up a headache patient. It clearly shows the impact of therapy and objectively records headache characteristics. Sometimes, it may unearth existence of another headache disorder. It also gives the patient a tool to make meaningful decisions on managing their headaches.
Disability Assessment
Two common tools for measuring migraine disability are Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Scale (MIDAS). These give scores which indicate the degree of disability because of the headache. Treatment approaches may differ depending on how disabling the headaches are. Hence, they are important to know.
CONCLUSION
Approach to headache patients may seem challenging but systematic and structured approach will make the task easier. Careful and detailed history is the cornerstone for the diagnosis. Red flags in history, abnormalities detected during examination, and appropriate investigations will rule out potential secondary causes. Detailed history will also give many leads for choosing the right therapy for a patient with headache. Assessment of disability and encouraging the use of headache diaries will be rewarding for both the patient and the physician.
REFERENCES
- Rasmussen BK, Jensen R, Schroll M, et al. Epidemiology of headache in a general population—a prevalence study. J Clin Epidemiol. 1991;44(11):1147–57.
- Kulkarni GB, Rao GN, Gururaj G, et al. Headache disorders and public ill-health in India: prevalence estimates in Karnataka State. J Headache Pain. 2015;16:67.
- Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629–808.
- Dodick D. Pearls: headache. Semin Neurol. 2010;30:74–81.
- Scher AI, Midgette LA, Lipton RB. Risk factors for headache chronification. Headache. 2008;48:16–25.
- Lipton RB, Silberstein SD, Dodick DW. Overview of diagnosis and classification. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolff's Headache and Other Head Pain. 8th ed. New Delhi: Oxford University Press; 2008. pp 29–43.
- Giffin NJ, Ruggiero L, Lipton RB, et al. Premonitory symptoms in migraine: an electronic diary study. Neurology. 2003;60:935–40.
- Russell MB, Olesen J. A nosographic analysis of the migraine aura in a general population. Brain. 1996;119:355–61.
- Lai TH, Fuh JL, Wang SJ. Cranial autonomic symptoms in migraine: characteristics and comparison with cluster headache. J Neurol Neurosurg Psychiatry. 2009;80(10):1116–9.
- Chang CL, Donaghy M, Poulter N. Migraine and stroke in young women: case control study. The World Health Organization Collaborative Study of cardiovascular disease and steroid hormone contraception. BMJ. 1999;318:13–8.
- Levy MJ, Matharu M, Goadsby PJ. Chronic headache and pituitary tumors. Curr Pain Headache Rep. 2008;12(1):74–8.
- Mitsikostas DD, Ashina M, Craven A, et al. European Headache Federation consensus on technical investigation for primary headache disorders. J Headache Pain. 2015;17:5.