Headaches: a comprehensive review

This excellent summary on headaches was written by a friend at Harvard, Dr. Ula Jurkunas. It is comprehensive and will answer questions about what one has to consider when headaches change in character. 

Headache and the Eye

Ula Jurkunas, MD, John W. Gittinger, JR, MD
Compr Ophthalmol Update. 2004;5(4) 
Headaches that present to an ophthalmologist include migraine, facial pain syndromes, and pain associated with cranial neuropathies, orbital, and ocular disease. Some headaches are symptoms of medical emergencies, placing the ophthalmologist in the front line of their recognition and management.
Headache and ocular pain are frequent complaints in ophthalmic practice. Clinically a clear distinction between headache, facial pain, and eye pain is not always apparent, but when present, it helps in the diagnostic approach. In this update we will categorize pain syndromes into migraines, facial pain with or without Horner’s syndrome, and headaches associated with other cranial nerve involvement. Intraocular findings may be manifestations of both ocular and systemic pathology. The goal is to present the most common and the most ominous headache presentations.
The most common definable headache syndromes are those designated migraine, with a prevalence of 5-25% and a marked female preponderance. In 2004, the Headache Classification Committee of the International Headache Society separated migraine syndromes into two main groups: migraine with and without aura.[1]
Migraine without aura, or common migraine, represents more than half of migraine headaches. Most often the headache is unilateral, variable in frequency, and lasts a minimum of 4 hours.[1-3] Unilaterality is less common in children (approximately 20%). The pain is usually throbbing or pulsating, moderate to severe, and aggravated by physical activity, bright lights, and loud noises. A clear relationship with menstrual cycle has been established.[1] Associated symptoms are nausea, anorexia, and photophobia—the latter possibly from irritation of the trigeminal nerve. Activation of the trigeminal autonomic reflex arc also accounts for sympathetic dysfunction during the attacks, such as delayed dilation of pupil in the darkness on the symptomatic side.[2,4,5] Patients with autonomic symptoms, such as eyelid edema, redness, lacrimation, or nasal congestion, during the migraine attacks are more likely to respond to sumatriptan, a serotonin receptor agonist.[6] A hallmark of migraine without aura is the absence of permanent neurological deficits.[2]
Migraine with aura, formerly called classic migraine, constitutes 10-35% of migraines and consists of aura, headache, and postheadache period. The aura is a transient cortical or brain stem dysfunction of gradual onset and less than 60 minutes duration. Cerebral blood flow reduction above ischemic threshold has been demonstated.[1] Diagnostic criteria include a nor mal neurological examination and absence of an underlying organic disorder.[2,7]
Auras can be divided into visual and neurological with both occurring at the same time in 88%.[2,7]Neurological auras are paresthesias, numbness, motor weakness, vertigo, aphasia, alexia, and even hemiplegia.[2,7] Paresthesias in extremities are especially common with visual auras, and symptoms in the extremities are characteristically associated with visual aura.[1] Visual auras are thought to orginate in striate cortex and range from an enlarging scintillating spot to a complete homonymous hemianopia. Scotomas may be positive or negative. The shimmering border of scintillating scotomas are colored lines forming angles and polygons to produce so-called fortification figures that usually progress from central field to the periphery.[2]The persistence of visual aura following bilateral enucleation and its simultaneous binocular nature proves these originate in the brain, not the eye.[2] Although recurrent transient monocular visual loss without headache and with complete recovery in young persons has been considered a variant of migraine, this phenomenon clearly must emanate from retina and optic nerve.[2,7]

Multiple mechanisms have been proposed in an attempt to explain the unique symptoms of migraine headache and to aid in management of this challenging disorder. Despite the success of conventional pharmacologic therapy of migraine with nonsteroidal anti-inflammatory drugs, caffeine, and calcium channel blockers, there are reports of treatment with botulinum toxin injections to the cranial musculature and injections of lidocaine with epinephrine to block the branches of the ophthalmic nerve.
[10-13]Headache on the contralateral side typically follows aura and lasts for several hours. Other visual symptoms in migraine are micropsia, macropsia, diplopia or polyopia, halos, movement of stationary objects, changes in color, and even for med visual hallucinations.[2] Migraine with aura does carry a small risk of ischemic stroke.[9,10]
Lasting neurological defects, including visual field defects, should prompt neuroimaging.[2,8,9] Of particular interest to the ophthalmologist is the novel notion that there might be increased prevalence of glaucomatous visual field defects in migraineurs.[7,14]
Headache may be associated with an ipsilateral defect in oculosympathetic pathways—Horner’s syndrome (HS) characterized by ptosis, miosis, and anhidrosis. The anisocoria is more apparent in dim light. The abnormal pupil is smaller, and pupillary reactions to light remain intact. Conventional pupillophar macological testing with cocaine and hydroxyamphetamine may be problematic because the ophthalmic solutions are difficult to obtain and the results are hard to interpret.[15-17] A few recent reports suggest that reversal of anisocoria with alpha-adrenergic agonists may be diagnostic of HS.[18] If this is shown to be a reliable test, it will greatly simplify pharmacologic diagnosis.
Causes of headache and third-order HS are listed in Table 1 . Because it can lead to stroke, internal carotid artery dissection (CAD) should always be considered in acute HS.[19-21] The classic presentation is cervical or facial pain radiating to the ipsilateral eye, but in 10% of cases the HS is the only sign.[22,26] Other manifestations of CAD are lightheadedness, bruits, syncope, amaurosis fugax, dysgeusia (foul taste), and cranial nerve palsies (VI, IX, XI, XII).[23] Marfan’s syndrome and fibromuscular dysplasia predispose to spontaneous CAD, which is also caused by direct trauma, whiplash injury, or chiropractic cervical manipulation.[24,25] Consideration of CAD should prompt an urgent evaluation with magnetic resonance imaging and magnetic resonance angiography and a neurological consultation for possible admission for anticoagulation (Figure 1).[23-25] While CAD is usually benign, it may cause life-threatening thromboembolic events. Even after the resolution of CAD by imaging, the HS may persist.[22]
 Top: Magnetic resonance angiography of right carotid artery dissection 2 cm from bifurcation (on left side). Bottom: Magnetic resonance angiography of right carotid artery dissection with clot in the wall (on left side). Dissection stops below skull base. Images contributed by Philip Kousoubris, MD.

Acute treatment consists of tapering dose of prednisone, methysergide (Sansert
®, Novartis, East Hanover, NJ), sumatriptan, or dihydroergotamine. Calcium channel blockers, such as verapamil, are used for prophylaxis. Avoidance of precipitants, such as alcohol and vasodilators, is recommended. A variant of CH that is distinguished by its dramatic response to indomethacin prophylaxis is chronic paroxysmal hemicrania.[31] Facial pain syndromes not associated with HS include trigeminal neuralgia, atypical facial pain syndrome, and temporomandibular joint syndrome ( Table 3 ).[32-34]Another headache plus HS entity is cluster headache (CH)—sudden, severe, lancinating pain that often awakens the patient at night.[27,32] Cluster headache characteristically attacks men between 20 and 40 years of age, is unilateral, and when recurrent affects the same side (85%) ( Table 2 ).[1] Orbital myositis, cavernous sinus lesions, and arteriovenous malformations have been confused with CH, leading some to advocate imaging.[28-30]
Idiopathic stabbing headache resembles trigeminal neuralgia and consists of icepick-like pains in the temple and orbit and may be associated with migraine, cluster, and tension headaches. This jabs or jolts syndrome consists of transient knife-like pains lasting less than 1 minute without any structural abnormalities.
A history of facial skin cancer excision along with pain and numbness or hyperesthesia in the distribution of the cranial nerve V should prompt consideration of neurotrophic spread of carcinoma along trigeminal or facial nerves, including squamous cell, basal cell, and nasopharyngeal cancers, as well as sinus and salivary gland tumors.[35-38] Such recurrences may manifest years after the original surgery. Neuroimaging may be normal.[35] These tumors may travel along the nerve into the cavernous sinus and Meckel’s cave.[38]

Orbital and cavernous sinus involvement secondary to HZV occlusive vasculitis may result in numerous posterior pole manifestations as well as cranial nerve palsies, most often cranial nerve III. A severe headache not related to dermatomal distribution, along with focal neurologic findings, indicates an intracranial vasculitis that is life-threatening and may present even several months after acute HZO infection.
[39,41-43] A young patient with HZO or bilaterality should raise the question of HIV infection.[44,45] Postherpetic neuralgia, persistent chronic pain after acute infection, is more prevalent with advancing age and occurs in 50% of patients in the sixth and seventh decades of life.[46,47] Treatment of HZO is outlined in Table 4 .In herpes zoster ophthalmicus (HZO), trigeminal der matomal involvement produces pain that may precede the vesicular eruption by several days. The patient may experience flushing, hypesthesias, and pain secondary to acute neuroganglionitis upon the reactivation of the latent herpes zoster virus (HZV).[39] Many patients are elderly, immunocompromised, or have neoplasia or blood dyscrasias. Spread of virus through trigeminal nerve sensory branches involves frontal and nasociliary nerve branches. In these cases, the pain may be exacerbated by corneal involvement, iridocyclitis, scleritis, or anterior segment ischemia from 360° perilimbal vasculitis. Marked elevation in intraocular pressure in 10% of patients is produced by trabeculitis and endotheliitis.[39-41]
The presentation of headache and ptosis will most likely unveil a painful cranial nerve III palsy that is usually of microvascular or aneurysmal etiology. Vascular risk factors, such as diabetes and hypertension, predispose to microcvascular palsies. The pupil is involved in only about 10% of microvascular palsies.[39,48] If the palsy does not remit within about 12 weeks, further testing is indicated to rule out mass lesion or myasthenia gravis.[39,49,50]
Isolated, painful cranial nerve IV or VI palsy may also be microvascular. Rheumatoid arthritis and other inflammatory disorders cause trochleitis.[51] Patients present with restricted elevation on adduction and tenderness in the superomedial orbit that may respond to local corticosteroid injections.[51] Sudden, painful cranial nerve VI palsy in an adult is most commonly of microvascular origin.[52,53] Work-up with neuroimaging, lumbar puncture, and/or edrophonium testing is warranted when there is bilaterality, progression, a history of malignancy, or no resolution within 3 months. Other indications for imaging are persistent pain or age less than 40 years.[53,54]The sudden onset of painful, complete (with pupillary involvement) cranial nerve III palsy is a posterior communicating artery aneurysm until proven otherwise. The pupil may be spared initially, but it then becomes involved in the first 24 hours. Such cases require emergency medical resonance imaging or medical resonance angiography.[39]
Painful abducens palsy with loss of tearing and/or involvement of second division of the trigeminal nerve may be caused by nasopharyngeal or metastatic carcinoma in the sphenopalatine fossa.[39] In the cavernous sinus, cranial nerve VI is vulnerable and is also affected by lesions mentioned in Table 5 .
Idiopathic paralysis of the facial nerve, or Bell’s palsy, may be accompanied by pain that usually fades within weeks. Severe and persistent pain inside the ear followed by the facial palsy sug gests the Ramsay Hunt syndrome, herpes zoster oticus (Figure 2). Inspection of the external auditory canal and skin behind the ear usually reveals vesicles. Other features are hearing loss, vertigo, and lymph node enlargement. Acyclovir is the treatment of choice.[55,56]
Ramsay Hunt syndrome with herpes zoster oticus

Table 5 highlights processes causing either isolated or multiple cranial neuropathies. In the cavernous sinus, blockage of venous outflow causes proptosis and chemosis. Pain is usually present due to involvement of trigeminal nerve. Bilaterality also suggests cavernous sinus involvement.
High-flow carotid-cavernous fistulas manifest as severe proptosis, chemosis, ophthalmoplegia, loss of vision, and bruit. Nevertheless, posterior-draining low-flow dural AV fistulas may present with painful ocular motor nerve palsy without congested orbital features.[57] Cavernous sinus thrombosis is usually accompanied by the systemic manifestations of sepsis. Mucor mycosis and aspergillosis should be ruled out in these cases.[58]
A nonspecific noninfectious granulomatous inflammation of cavernous sinus and superior orbital fissure, Tolosa-Hunt syndrome, manifests as severe retro-orbital pain with ipsilateral ophthalmoplegia.[59] Imaging studies are usually nonspecific but occasionally show enlargement of extraocular muscle bellies and optic nerve, suggesting an etiologic continuum with idiopathic orbital inflammation, also called pseudotumor of the orbit (Figures 3-5).[60,64] A hallmark of Tolosa-Hunt syndrome is a rapid response to corticosteroids; nevertheless, steroid responsiveness is nonspecific as other conditions may improve transiently.
Right orbital pseudotumor in adult. Computed tomography of orbits shows right scleral thickening, stranding of orbital fat, and thickening of extraocular muscle tendons.
Computed tomography scan of bilateral orbital pseudotumor in 2-year-old child.
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Tolosa-Hunt syndrome. Arrow shows signal enhancement at left orbital apex and cavernous sinus.
Similarly, idiopathic orbital inflammation has various presentations and may be a diagnosis of exclusion.[61,62] Patients experience acute retro-orbital pain with proptosis and soft tissue and orbital congestion. Radiologic findings and clinical course are usually suggestive of the diagnosis (Figure 3).[63] An unusual clinical presentation or course may require an orbital biopsy.[61-63]
Children have a higher prevalence of bilateral involvement and anterior chamber inflammation than adults (Figure 4).[63,65] Bilaterality in adults could be due to underlying systemic vasculitis. After infectious etiologies have been ruled out, the treatment of choice is oral prednisone.[61,64] Other causes of orbital pain are trauma, infection, cancer, or vasculitis ( Table 6 ).
The eye is a transparent, superficial organ, and routine examination techniques readily identify ocular causes of headache. There has been ongoing debate whether uncorrected refractive error causes asthenopia or eye strain. Although there is little evidence that refractive error or strabismus directly causes headaches, appropriate correction may improve symptoms.[66,67] Untreated hyperopia can result in persistent attempts to accommodate, thus relaxing accommodation with hyperopic prescription may lessen the eye discomfort. Accommodative spasm usually occurs in young patients and presents with eye pain, myopia, and miosis when doing near work. Management is reassurance and general relaxation techniques.
Any ocular surface disease should be treated. Uveal and scleral inflammation should be addressed with anti-inflammatory therapy and work-up for underlying systemic causes.[67]
Acute elevation in intraocular pressure is usually associated with pain, while an eye with a similar pressure of gradual onset may be asymptomatic.[67] While acute angle-closure glaucoma is the most common painful glaucoma, some for ms of secondary open- and closed-angle glaucoma are associated with acute pressure spikes and pain ( Table 7 ).
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Retrobulbar optic neuritis presents with subacute loss of vision and pain on eye movement with nor mal-appearing optic nerves initially.[68] In papillitis there is disk swelling. Patients are usually women between 15 and 45 years of age. Magnetic resonance imaging should be performed to look for evidence of demyelination elsewhere, as treatment with high-dose corticosteroids may delay the onset of clinically definite multiple sclerosis (MS). Immunomodulatory therapies used in relapsing/remitting MS, such as beta-interferons, may be appropriate early therapy in these patients with optic neuritis and evidence of brain demyelination (i.e., those patients therefore at higher risk for the subsequent development of MS).[69,70]
Temporal headache in an elderly person should alert one to a possibility of giant cell arteritis, which is an emergency ( Table 8 ).[71] Appropriate clinical assessment and evaluation with sedimentation rate and C-reactive protein should be targeted at this group of patients. If there is already visual loss in one eye from anterior ischemic optic neuropathy or central retinal artery occlusion and this diagnosis is suspected, corticosteroid therapy should be initiated immediately and followed by temporal artery biopsy. The main goal is prevention of contralateral eye involvement.
Bilateral disk edema in a patient with headache most often represents papilledema and warrants urgent neuroimaging to rule out tumor, hydrocephalus, or bleeding. The headache of increased intracranial pressure need not be severe, but it is often present on awakening and associated with vomiting. When neuroimaging is normal, the next step is referral for lumbar puncture to measure intracranial pressure and determine cerebrospinal fluid (CSF) composition. The diagnosis of pseudotumor cerebri, or idiopathic intracranial hypertension, is established by normal neuroimaging and CSF composition with elevated intracranial pressure. The ophthalmologist should not consider this entity benign, as chronic papilledema may lead to blindness. Treatment includes weight reduction, diuretics (especially acetazolamide), shunting, and optic nerve sheath fenestration.
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Low intracranial pressure also may cause headache and is encountered after lumber puncture or with spontaneous CSF leaks.[74] Imaging may show thickened meninges on T1 that enhance with gadolinium.
Headache from elevated blood pressure may be accompanied by bilateral disk swelling, a variant of malignant hypertension, in which medical treatment may preserve life and vision.
We all learned in medical school that a patient reporting the worst headache of his or her life may have subarachnoid hemorrhage.
Headaches that present to an ophthalmologist include migraine, facial pain syndromes, and pain associated with cranial neuropathies, orbital, and ocular disease. Some headaches are symptoms of medical emergencies, placing the ophthalmologist in the front line of their recognition and management.

Headache and the Eye

Ula Jurkunas, MD, John W. Gittinger, JR, MD
Compr Ophthalmol Update. 2004;5(4) 

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