ACCURATE DIAGNOSIS OF URGENT HEADACHE

Stephanie J. Nahas, MD, MSEd Thomas Jefferson University Hospital Philadelphia, PA Introduction The diagnosis of acute headache can be challenging, but an orderly approach will lead to appropriate management decisions. Crucial elements of a systematic evaluation include a thorough history, focused general medical and neurologic examinations, and laboratory testing and neuroimaging when indicated. An important first step is distinguishing primary (no apparent cause) from secondary (identifiable underlying pathology) headaches. Primary headache syndromes are diagnosed according to criteria based on clinical features.1 Although the probability of secondary headaches increases in the urgent setting, most patients with acute headache have a primary disorder.2 Does the patient have migraine? A simple three-question inventory called ID Migraine serves as a moderately sensitive (81%) and specific (75%) screening tool with excellent positive predictive value (93%) for the presence of migraine in clinic patients (Table 1). A patient in an urgent care setting probably already fulfills the second question (disability), so simply asking about nausea and photosensitivity should point in the direction of migraine. It is important not to forget that secondary headaches can mimic migraine, so before jumping to this diagnosis, assess for red flags which suggest the possibility of secondary headache. Using the SNOOP mnemonic (Table 2) will help identify them. Comfort signs, such as a longstanding, stable, or slowly progressive disorder; normal neurologic exam; typical triggers, clinical features, and history; and response to appropriate medication, also are important to recognize as indicators of a primary disorder, and may offset certain lesser red flags, thus avoiding unnecessary diagnostic testing, which can be costly and waste time. If secondary headache is excluded, diagnostic criteria dictate the diagnosis of primary headache. Table 1. ID Migraine
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1. Nausea: Are you nauseated or sick to your stomach when you have a headache? 2. Disability: Has a headache limited your activities for a day or more in the last 3 months? 3. Photophobia: Does light bother you when you have a headache? 2 out of 3 symptoms: 93% migraine 3 out of 3 symptoms: 98% migraine Lipton, et al., 2003 Table 2. Red Flags: SNOOP4 stands for Systemic symptoms Secondary risk factors Neurologic symptoms/signs Onset Older Prior history for example Fever, weight loss HIV, cancer, immune suppression Altered consciousness, focal deficits Split-second, thunderclap New after age 50 First, newly progressive, or different from usual Dramatic change upright vs. recumbent think of Infections, metastatic cancer, carcinomatous meningitis Encephalitis, mass lesion, stroke Subarachnoid hemorrhage, and others (see Table 3) Giant cell arteritis Any secondary cause can lead to change in pattern Intracranial hypotension, orthostatic dysautonomia Increased intracranial pressure

S N O O P

Positional

Visual obscurations Papilledema Modified from Dodick, D.W., 2003

The initial assessment should be swift but thorough. Focus questioning to the history of the evolution of the current headache, its clinical characteristics, and any associated features or phenomena. Pay particular attention to the following in the physical examination: Vital signs: fever, hypertension, hypotension Carotid and vertebral arteries: palpate for tenderness, auscultate for bruits (listen for intracranial bruits as well) Temporal arteries: palpate for tenderness and presence of pulses Neurologic examination o Mental status: level of consciousness, presence of delusions or hallucinations o Pupils and fundi: pupillary shape, symmetry, and reactivity; assess for papilledema and retinal hemorrhage o Vision: diplopia, dysconjugate gaze, injection, visual field deficit o Neck: discern between stiffness from muscle spasm and rigidity from meningeal irritation o Extremities: focal weakness or sensory loss, limb ataxia, asymmetric reflexes, Babinski sign o Gait and station: ataxia, hemiparesis, Romberg sign Identifying red flags (1) Sudden onset of severe headache (thunderclap headache). While subarachnoid hemorrhage should be the diagnosis that springs to mind first and foremost in the case of the sudden onset of severe headache, many other etiologies can cause thunderclap headache (Table 3). The first step is brain computed tomography (CT) to look for obvious bleed, then lumbar puncture if the CT is negative, to look for evidence of occult bleeding and to check cerebrospinal fluid (CSF) pressure. Even with bloodless CT and CSF, vascular imaging with magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) (since noninvasive and obtainable more swiftly, these are preferable to formal angiogram in this circumstance) is suggested to exclude dissection, unruptured aneurysm, and reversible cerebral vasoconstriction syndrome (RCVS), the latter of which is becoming increasingly recognized as a cause of thunderclap headache, especially recurrent thunderclap headache.5 Magnetic resonance venography (MRV) or computed tomographic venography (CTV) will identify cerebral venous thrombosis, which should be suspected if there is papilledema or a procoagulant state (hereditary, autoimmune, hormonal). While spontaneous intracranial hypotension is usually not of thunderclap onset, some cases have been described, and this should be suspected especially if the headache is positional (better with recumbency) or associated with magnetic resonance imaging (MRI) findings of pachymeningeal enhancement, pituitary engorgement, and hindbrain descent (also termed brain sag or false Arnold-Chiari malformation) (Figure 1). The diagnosis can be confirmed with lumbar puncture (opening pressure will be less than 10 cm CSF, sometimes unmeasurable or even negative) or radionucleotide myelogram/cisternogram (rapid CSF turnover is evidenced by early appearance of the tracer in the kidneys/bladder and failure of tracer to appear in the cerebral conxevities after 16-24 hours {Figure 2], and the site of leak might also be seen).6 MRI with gadolinium and general medical evaluation will reveal most other causes of thunderclap headache.7 A diagnosis of primary thunderclap headache may be assigned when all appropriate investigation is negative. Table 3. Differential Diagnosis of Thunderclap Headache8 Vasular Etiologies Subarachnoid hemorrhage Aneurysmal thrombosis or expansion Cervical arterial dissection Reversible cerebral vasoconstriction syndrome Cerebral venous thrombosis Hypertensive crisis Pituitary apoplexy Retroclival hematoma Non-Vascular Etiologies Spontaneous intracranial hypotension/hypovolemia Meningitis Sinusitis (especially sphenoid) Colloid cyst of the third ventricle Primary cough, sexual, and exertional headache Primary thunderclap headache (idiopathic)

Modified from Nahas, S.J., 2010.

Figure 1: MRI findings in CSF hypotension/hypovolemia

On the left, pachymeningeal enhancement, and on the right, brain sag and pituitary engorgement. Figure 2: Radionucleotide myelogram/cisternogram in CSF hypotension/hypovolemia

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Tracer appears early in the bladder and kidneys, and never reaches the cerebral convexities. The site of leak is not detectible on this study. (2) Worsening headache pattern. A mass lesion may be the most feared etiology of worsening headaches of recent onset. These often present with focal neurologic deficits or papilledema, but if the mass is slow-growing or in a silent area, progressive headache could be the only symptom. Historical clues which may suggest the possibility of a mass manifesting only as headache include known cancer (metastatic disease), HIV (toxoplasmosis), immune suppression (empyema), and recent fall in an elderly patient (subdural hematoma). If a mass lesion is suspected, MRI with gadolinium is the best test to detect it. CSF hypovolemia may also present as a progressively worsening headache, and is not always prominently orthostatic. Sometimes these headaches are only worse in the latter part of the day, or are paradoxically worse when lying down.

Two possibilities exist when headache progression occurs in the context of a well established primary disorder: 1) a primary or secondary superimposed headache disorder and 2) chronification of primary headache. Migraine and tension-type headache can become chronic over months to years in susceptible patients. Chronic daily headache, defined as headache on more days than not, is a primary disorder (except when a definite contributor is identified, such as excessive use of pain medication). Risk factors for chronification include high frequency of headaches, frequent use of acute medications, obesity, stressful life events, alcohol overuse, hypothyroidism, viral infections, head trauma, snoring, and sleep disturbances.9 When atypical clinical features are present, or exacerbating factors cannot be identified easily, further investigation should be considered. (3) Headache with systemic illness or systemic symptoms. Intracranial and extracranial infections, hypoxia and hypercapnia, dialysis, uncontrolled hypertension, hypotension, hypothyroidism, fasting, collagen vascular disorder, and arteritis are among the many systemic disorders can cause acute headache.10 Fever, neck stiffness, rash, fatigue, malaise, and arthralgias are particularly suggestive of this etiology. It is noteworthy that an acute infection isolated to the sphenoid sinus usually presents without nasal drainage; suspect it when a febrile headache involves facial paresthesiae or cranial nerve palsies. Giant cell arteritis is a preventable but underdiagnosed cause of blindness in the elderly. This should be suspected when an older person with headaches also notes fatigue and constitutional symptoms, attests to jaw claudication, or has temporal artery hardness and tenderness with a weak or absent temporal artery pulse. Even before confirmation that the erythrocyte sedimentation rate is elevated or inflammation is demonstrable on temporal artery biopsy, empiric treatment with steroids is justified. In patients with cancer, brain and leptomeningeal metastasis should be considered.11 (4) Headache with focal signs other than typical visual or sensory aura. Table 4 outlines clinical clues that are useful in differentiating neurologic transients of epileptic or vascular etiology from migraine aura. Toxic metabolic disorders may also cause headache with transient neurologic symptoms, but these rarely present with focal signs, and rather are characterized by prominent encephalopathy. More persistent neurologic deficits associated with headache suggest stroke, encephalitis, and mass lesions. Occasionally, CSF hypovolemia can manifest with signs referable to hindbrain dysfunction (visual disturbances, diplopia, tinnitus or other hearing changes, facial weakness or numbness, other bulbar signs, or altered consciousness), particularly when bran sag is severe. Transient visual obscurations, pulsatile tinnitus, and papilledema in an obese patient with normal imaging suggests intracranial hypertension, and lumbar puncture must be performed expeditiously, both for diagnostic and therapeutic purposes. Table 4. Transient Neurological Symptoms in Migraine, Epilepsy, and TIA Symptom Duration and spread Automatisms Gastrointestinal symptoms Migraine 5 to 60 minutes, with slow spread Unusual
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Abdominal pain (rare), nausea (common) Visual disturbances Simple positive or negative phenomena Paresthesiae Common (5 to 60 minutes) Level of consciousness Usually responsive Olfactory Very uncommon Aphasia Uncommon Dj vu Rare Modified after Bigal, et al., 2003

Epilepsy Brief, often shorter than 1 min, with rapid spread Frequent for complex partial seizures Rising epigastric sensation ("butterflies") Complicated visual phenomena Common (seconds to minutes) Often unresponsive More common Somewhat common Common

TIA Hours, sudden onset with rapid spread Very unusual Unusual Usually negative phenomena Common (hours) May be altered Very uncommon Very common Rare

(5) Headache triggered by cough, exertion, or orgasm. These headaches do not have secondary causes more often than headaches not associated with red flags, but suspect pathology if the headache is severe and unequivocally associated with the trigger. Valsalva-induced headache may indicate increased intracranial pressure, occipitocervical junction disorder, or a hindbrain malformation. Sometimes orgasmic headaches are due to subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, or mass lesions.13 Exertional headache sometimes represents a rare disorder termed cardiac cephalgia, an anginal equivalent.14

(6) Headache during pregnancy or postpartum. A pregnant or postpartum woman with a history of migraine or tension-type headache, who has a normal examination and a headache without atypical features, usually needs no investigation. In the presence of red flags, consider in particular cerebral venous thrombosis, stroke, preeclampsia, and pituitary apoplexy, especially in the third trimester or the early post-partum period.15,16 Diagnosing a primary headache disorder It is beyond the scope of this session to detail the diagnostic criteria1 of primary headaches, but a simple strategy aids in reaching the correct diagnosis. If the headache is difficult to classify, the possibility of secondary headache should be reconsidered. Primary headaches can be conceptualized in terms of frequency and duration of attacks. In syndromes of low-tomoderate frequency, headaches occur on fewer than 15 days per month; in high frequency, 15 or more days per month. Short duration is defined as less than 4 hours a day, long-duration 4 or more hours.17 Then using diagnostic criteria, one may assign the appropriate diagnosis (Table 5). Table 5: Common headache syndromes Frequency/ Duration Long (>4 hours) Chronic (15 or more days per month) Episodic (fewer than 15 days per month) Episodic migraine Episodic tension-type headache

Chronic migraine Chronic tension-type headache New daily persistent headache Hemicrania continua Short Cluster headache (<4 hours) Paroxysmal hemicrania SUNCT/SUNA Trigeminal neuralgia Hypnic headache Adapted from Lipton, R.B., et al., 2008 Low-to-moderate frequency headaches of long duration

Cough, exertional, sexual headache Idiopathic stabbing headache

These syndromes include episodic migraine and episodic tension-type headache. Tension-type headaches are bland. The pain tends to be bilateral, non-pulsating, mild to moderate in intensity, and not aggravated by activity. There is no nausea or vomiting, but either photophobia or phonophobia may be present. While very common, 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.2 In its fully featured form, pain typically is severe, throbbing, unilateral, aggravated by activity, and associated with nausea, photophobia, and phonophobia, but often, only some of these features are present, yet the headache is still classified as migraine. Two of the four pain characteristics above, accompanied by either nausea or photophobia and phonophobia, fulfills diagnostic criteria. Aura is not required in migraine diagnosis; only about 30% of patients with migraine experience aura, and usually with only some attacks. High-frequency headaches of long duration These syndromes include chronic migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Patients with chronic migraine often seek acute care when having a severe exacerbation, and can present in quite dramatic fashion. When a clear history of increasingly frequent and severe attacks over the course of weeks or months without other red flags is obtained, investigation is not required before empiric treatment. New daily persistent headache is as the name implies daily from onset. At initial presentation, as early in the course as possible, a thorough investigation should be done to exclude a multitude of potential 18 secondary disorders. Fairly commonly, this syndrome begins in the context of a viral illness, but often, no specific cause is found, despite an exhaustive search. Hemicrania continua is typified by constant unilateral pain with superimposed exacerbations, and is commonly mistaken for chronic migraine.19 Exacerbations are of variable duration and frequency. They are associated with ipsilateral autonomic features, such as conjunctival injection, lacrimation, and ptosis, although migrainous features can coexist. In chronic migraine, autonomic

features may also occur with exacerbations, compounding the diagnostic challenge. In practice, many patients indeed have crossover syndromes, and this is reflected in the ongoing debate whether to classify hemicrania continua along with migraine, with other headaches characterized by prominent autonomic features, or as some other primary headache. Headaches of shorter duration High-frequency syndromes include the trigeminal autonomic cephalgias: cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with autonomic features (SUNA) syndromes; and also trigeminal neuralgia, hypnic headache, and exertional headaches. The trigeminal autonomic cephalgias are typified by unilateral pain in the trigeminal distribution with ipsilateral autonomic features (conjunctival injection, lacrimation, nasal congestion, rhinorrhea, eyelid edema, forehead or facial sweating, miosis, or ptosis). Cluster headache is the most common syndrome. Cluster pain is described as sharp, boring, drilling, knife-like, piercing, or stabbing. 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. Patients are agitated and restless. Attacks have a predilection for specific times of day: nocturnal most commonly, and sometimes early morning and mid-afternoon. Attacks may be as infrequent as every other day, or as frequent as 8 per day, with an average of 2-3 per day. Attacks tend to come in cycles lasting weeks to months with remission periods of months 20 to years, although a subset of patients experience attacks daily without remission. Paroxysmal hemicrania is similar to cluster headache with 3 main exceptions: 1) greater frequency (more than 5 per day at least half of the time); 2) shorter duration (2 to 30 minutes); 3) absolute response to therapeutic doses of indomethacin. Other distinguishing characteristics are that it is more common in women, and attacks do not have nocturnal predilection.21 SUNCT attacks are only seconds to minutes in duration, and can occur hundreds of times per day. They are characteristically dramatic with prominent tearing. A cutaneous trigger may be present, which can lead to misdiagnosis of trigeminal neuralgia of the ophthalmic division. SUNA syndrome is similar to SUNCT, but attacks last slightly longer and are less frequent.21 In trigeminal neuralgia, attacks are very brief, electric-like jolts of pain involving one or more unilateral trigeminal distributions. Some patients experience volleys of pain at such a high rate that overall pain seems to be nearly constant. Cutaneous triggers (e.g., stroking the skin, cold air on the face, eating or drinking, brushing teeth or hair) are almost universal, and autonomic features are almost never present. Hypnic headache affects older patients, and is characterized by short-lived attacks (typically 30 minutes) of head pain that causes awakenings at a consistent time each night. Pain is usually bilateral and mild to moderate, without autonomic or migrainous features.22 Headaches triggered by cough, exertion, and sexual activity include the disorders named for these triggers. Especially in patients presenting urgently, these headaches may only be diagnosed after an exhaustive and methodic search for secondary causes.13 Summary Accurate diagnosis of acute headaches requires a thorough systematic evaluation. Here is presented an orderly approach to differential diagnosis. The most important first step is to decide how likely a secondary cause to the headache exists, and then to proceed to investigate this possibility expeditiously to guide diagnosis and treatment. References 1. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders. Cephalalgia 2004;24:1-160. 2. Friedman BW, Grosberg BM. Diagnosis and management of the primary headache disorders in the emergency department setting. Emerg Med Clin North Am. 2009;27(1):71-87.

3. Lipton RB, Dodick D, Sadovsky R, Kolodner K, Endicott J, Hettiarachchi J, et al. A self-administered screener for migraine in primary care: The ID migraine validation study. Neurology 2003;61(3):375-382. 4. Dodick DW. Clinical clues and clinical rules: Primary vs secondary headache. Advanced Studies in Medicine. 2003;3(6 C). 5. Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med 2007;146(1):34-44. 6. Mokri B. (2005). Spontaneous intracranial hypotension spontaneous CSF leaks. Headache Currents 2005;2(1):11-22. 7. Yu YE, Schwedt TJ. Abrupt-onset severe headaches. Semin Neurol 2010;30(2):192-200. 8. Nahas, SJ. Diagnosis of the acute headache. 2010. Available from: www.medlinkneurology.com. 9. 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. 10. Gladstone JP and Bigal ME. Infectious, toxic, and metabolic headaches. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolffs Headache and Other Head Pain. New York: Oxford University Press 2008:247-82. 11. Ward TN, Levin M. Headache in giant cell arteritis and other arteritides. Neurological Sciences. 2005;26(SUPPL. 2):S134-7. 12. Bigal ME, Lipton RB, Cohen J, Silberstein SD. Epilepsy and migraine. Epilepsy Behav 2003;4(Suppl 2):13-24. 13. Wang S-, Fuh J-. The "other" headaches: Primary cough, exertion, sex, and primary stabbing headaches. Curr Pain Headache Rep. 2010;14(1):41-6. 14. Bini A, Evangelista A, Castellini P, Lambru G, Ferrante T, Manzoni GC, et al. Cardiac cephalgia. Journal of Headache and Pain. 2009;10(1):3-9. 15. Contag SA, Mertz HL, Bushnell CD. Migraine during pregnancy: Is it more than a headache? Nature reviews.Neurology. 2009;5(8):449-56. 16. 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. 17. Lipton RB, Silberstein SD, Dodick DW. Overview, diagnosis and classification. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolffs Headache and Other Facial Pain. New York: Oxford University Press, 2008:6-26. 18. Mack KJ. New daily persistent headache in children and adults. Curr Pain Headache ep. 2009;13(1):47-51. 19. Peres MFP, Valena MM, Gonalves AL. Misdiagnosis of hemicrania continua. Expert Review of Neurotherapeutics. 2009;9(9):1371-8. 20. Halker R, Vargas B, Dodick DW. Cluster headache: Diagnosis and treatment. Semin Neurol. 2010;30(2):17585. 21. Goadsby PJ, Cittadini E, Cohen AS. Trigeminal autonomic cephalalgias: Paroxysmal hemicrania, SUNCT/SUNA, and hemicrania continua. Semin Neurol. 2010;30(2):186-91. 22. Obermann M, Holle D. Hypnic headache. Expert Review of Neurotherapeutics. 2010;10(9):1391-7.