Headache and the eye Rima M. Dafer a and Walter M. Jay b

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1 Headache and the eye Rima M. Dafer a and Walter M. Jay b a Department of Neurology and b Department of Ophthalmology, Loyola University Medical Center, Maywood, Illinois, USA Correspondence to Rima M. Dafer, MD, MPH, Department of Neurology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA Tel: ; fax: ; [email protected] Current Opinion in Ophthalmology 2009, 20: Purpose of review Visual disturbances and ocular symptoms are common manifestations of two primary headache disorders, migraine and trigeminal autonomic cephalalgias, and many secondary headache disorders. Recent findings Structural lesions have been described with trigeminal autonomic cephalalgias. A systematic diagnostic evaluation including neuroimaging with assessment of intracranial and cervical vasculature, and the sellar and paranasal regions is recommended in every patient presenting with symptoms indicative of trigeminal autonomic cephalalgias for the first time. Summary Ophthalmologists are often the first physicians to evaluate patients presenting with headaches and ocular pain or visual symptoms. Knowledge of primary and secondary headache disorders, a detailed history, and a thorough clinical examination are prerequisites for accurate diagnosis and appropriate management. Keywords headache, migraine, ophthalmoplegia, trigeminal autonomic cephalalgia Curr Opin Ophthalmol 20: ß 2009 Wolters Kluwer Health Lippincott Williams & Wilkins Introduction Visual disturbances and ocular symptoms are common manifestations of certain primary headache disorders and many secondary headache disorders. The main primary headache disorders that we discuss are migraine, trigeminal autonomic cephalalgias, and hemicrania continua. Trigeminal autonomic cephalalgias can be subdivided into cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing. We will also review a number of secondary headache disorders with ocular symptomatology. Primary headache disorders Three main primary headache disorders are associated with prominent ophthalmological manifestations, including migraine, trigeminal autonomic cephalalgia, and hemicrania continua [1]. The latter is discussed under trigeminal autonomic cephalalgias (TACs) due to the similarity in clinical symptomatology. Migraine Migraine is a common paroxysmal primary headache disorder affecting 28 million people in the USA [2]. Migraine is often associated with ophthalmologic manifestations, including ocular pain, visual disturbances, and ophthalmoplegia (Table 1). Visual aura occurs in 15 20% of migraineurs, and usually precedes the headache onset. Typical migraine aura is described as scintillating scotoma, fortifications, stereotyped visual hallucinations, micropsia or Alice in Wonderland, or constriction of the visual field. The duration of the visual aura typically lasts 20 min, rarely up to 60 min [1]. Migraine aura without headache or acephalgic migraine is seen in 3 5% of migraineurs, often in older patients with a remote history of migraine [1]. The visual manifestations are similar to that of migraine with aura. The condition should be differentiated from transient ischemic attack and occipital lobe seizures. Retinal migraine is characterized by recurrent episodes of unilateral transient visual loss lasting minutes to 1 h. Headache is not a prominent feature of the disorder. Retinal migraine should be differentiated from ischemic transient monocular blindness or amaurosis fugax associated with internal carotid artery disease [1,3 6]. Diplopia may occur in basilar-type migraine, a subtype of migraine, in which headache is accompanied by neurological symptoms emanating from either brainstem or bilateral hemispheric disturbance. Dizziness, dysarthria, ataxia, tinnitus, hearing loss, dysarthria, bilateral paresthesias, altered consciousness, and syncope may occur [1,7 9]. The condition is more common in adolescent ß 2009 Wolters Kluwer Health Lippincott Williams & Wilkins DOI: /ICU.0b013e d

2 2 Ocular manifestations of systemic disease Table 1 Visual symptoms in migraine subtypes Migraine subtype Headache Visual symptoms Migraine with typical aura Unilateral or bilateral, throbbing, Zigzag lines, scintillating scotomata, blurred vision, visual distortion and fortifications, visual field defect/tunnel vision, micropsia Retinal migraine Not prominent Transient monocular blindness Basilar-type migraine Unilateral or bilateral, throbbing, Ophthalmoplegia Ophthalmoplegic migraine Unilateral or bilateral, throbbing, Ophthalmoplegia, typically oculomotor neuropathy Migraine aura without headache Absent Zigzag lines, scintillating scotoma, blurred vision, visual distortion and fortifications, visual field defect/tunnel vision, micropsia girls and young women. Basilar-type migraine should be differentiated from demyelinating, inflammatory, vascular, or neoplastic conditions affecting the brainstem, and is a diagnosis of exclusion. Another form of migraine variant is ophthalmoplegic migraine, a rare form of childhood neuralgia, often associated with migraine-like headache and periorbital pain. The oculomotor nerve is most commonly involved followed by the abducens and rarely the trochlear nerve. The ophthalmoplegia may last from days to months. Remission is usually spontaneous. The condition has been recently reclassified as a demyelinating neuropathy of the ocular cranial nerves. Differential diagnosis includes conditions involving the parasellar region, orbital, and posterior fossa leading to headache and ophthalmoplegia. Enduring thickening of the cranial nerve affected has been reported on MRI [10]. The pathophysiology of migraine is not clearly understood. Cortical spreading depression (CSD) is thought to be the neuronal process underlying visual aura. CSD, in turn, activates the trigeminovascular system and triggers pathophysiological mechanism of the migraine headache [11,12,13]. Management of migraine is targeted at acute treatment and preventive therapy. Acute migraine headaches may be treated with nonsteroidal anti-inflammatory drugs, triptans, or ergot alkaloids. Triptans and ergot alkaloids are contraindicated when basilar-type migraine is suspected. Patients with frequent migraine attacks usually require long-term preventive therapy. Options include beta-blockers, calcium channel blockers, tricyclic antidepressants, and antiepileptic agents such as topiramate and valproic acid. Trigeminal autonomic cephalalgias TACs are primary neurovascular headache disorders characterized by severe, strictly unilateral, typically retro-orbital or periorbital, short-lasting headaches accompanied by prominent cranial facial parasympathetic autonomic features [1,14 ]. TACs include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). TACs subtypes differ in duration, frequency, and rhythmicity of the attacks and in the response to treatment (Table 2). Cluster headache is the most frequent of the TACs. It is characterized by attacks of severe excruciating periorbital or retro-orbital pain accompanied by ipsilateral cranial autonomic symptoms such as lacrimation or conjunctival injection, miosis, and ptosis [1]. It is typically seen in men in the third and fourth decade of life, commonly among smokers. The attacks occur once every other day or up to eight times a day and last 15 min to 3 h. Cluster headache may be episodic, with periods of remission between attacks, or chronic, in which attacks occur almost daily for a year or more. Circadian biological changes and neuroendocrine disturbances have suggested a pivotal role for the posterior hypothalamus in the pathogenesis of cluster headache [1,15]. Paroxysmal hemicrania is similar to cluster headache in that headaches are severe, strictly unilateral, orbital or supraorbital, accompanied by ipsilateral cranial autonomic features. Paroxysmal hemicrania may also be Table 2 Characteristics of trigeminal autonomic cephalgias and hemicrania continua Cluster Paroxysmal hemicrania SUNCT Hemicrania continua Age (years) > M : F ratio 3 : 1 1 : 2 1 : 2 1 : 3 Location Orbital/temporal Orbital/temporal Periorbital Orbital/temporal Duration of pain min 2 30 min 5 s to 4 min Minutes to days Frequency of attacks 1 every other day to 8 per day 1 40 per day per day Variable Response to indomethacin þ/ þþ þþ F, female; M, male.

3 Headache and the eye Dafer and Jay 3 episodic or chronic. The condition is more common in younger women in the second and third decades of age. The duration of the attacks is 2 30 min, with a frequency of 5 40 attacks a day. Paroxysmal hemicrania is characterized by absolute responsiveness to indomethacin [1]. SUNCT syndrome is characterized by short-lived attacks of unilateral moderate-to-severe stabbing or electric shock-like orbital or periorbital pain, accompanied by prominent lacrimation and conjunctival injection. The attacks are much more brief than those seen in other TACs, typically lasting s, and often recurring up to 200 times a day. The disorder has a male predominance, often affecting those in the fifth to seventh decades of life [1,16]. Hemicranium continuum is another primary headache disorder, similar in characteristics to TACs, and is included in the discussion for completeness. Hemicranium continuum is a daily continuous unremitting, strictly unilateral headache of moderate-to-severe intensity, accompanied by trigeminal autonomic features, sometimes with eyelid swelling or twitching. Patients may experience migrainous symptoms and ice-pick headaches. Like paroxysmal hemicranium, hemicranium continuum has female preponderance. Complete responsiveness to therapeutic doses of indomethacin is an essential criterion for the diagnosis according to the International Classification of Headaches Disorders II. Structural lesions have been described with TACs [17 20,21,22,23]. A systematic diagnostic evaluation including neuroimaging and assessment of intracranial and cervical vasculature and the sellar and paranasal regions is recommended in every patient presenting with symptoms indicative of TAC for the first time [21 ]. The periodicity of the attacks in TACs suggests involvement of a biological clock within the hypothalamus, with activation of nociceptive and autonomic pathways, specifically the trigeminal nociceptive pathways. Management of acute cluster headache attacks includes oxygen therapy, parenteral or nasal triptans, or ergot alkaloids. Preventive therapies are aimed at aborting a cluster headache and decreasing the number of attacks. These include prednisone, verapamil, lithium, and various antiepileptic drugs, mainly valproic acid, topiramate, gabapentin, pregabalin, and lamotrigine. Both paroxysmal hemicrania and hemicrania continua are characterized by absolute responsiveness to indomethacin. SUNCT is usually refractory to treatment, although antiepileptic drugs may be considered. Other interventions may include sphenopalatine ganglion and occipital nerve stimulation. Deep brain stimulation of the posterior hypothalamus has recently emerged as a potential treatment option for refractory chronic drug-resistant TACs. Secondary headache disorders Painful ophthalmoplegia may occur in patients presenting with headaches secondary to vascular conditions, such as aneurysm, carotid dissection, and carotid-cavernous fistula, and inflammatory disorders including giant cell arteritis (GCA), sarcoidosis, idiopathic orbital inflammatory diseases (IOIDs), and Tolosa Hunt syndrome. A systematic approach to the evaluation of painful ophthalmoplegia can lead to prompt recognition of serious disorders that can be associated with significant morbidity or mortality if left untreated [24]. IOID or orbital pseudotumor is an inflammatory disorder that involves one or multiple structures contained within the orbit. Prominent features include acute onset ocular pain, swelling, proptosis, ophthalmoplegia, and progressive optic neuropathy. The condition should be differentiated from systemic diseases such as Graves disease, Wegener s granulomatosis, sarcoidosis, malignancies, infectious diseases, or trauma. Management includes systemic immunosuppression with corticosteroids, or rituximab, in combination with surgery or radiation therapy [25,26]. Tolosa Hunt syndrome is a rare cause of painful ophthalmoplegia attributed to inflammatory granulomatous infiltration of the superior orbital fissure or cavernous sinus. It is characterized by unilateral periorbital or retro-orbital pain, ipsilateral ophthalmoparesis mainly oculomotor neuropathy, and less commonly trochlear or abducens cranial nerve palsies, ipsilateral paresthesias in the distribution of the ophthalmic division of the trigeminal nerve, and remarkable steroids responsiveness [24,27,28]. Ophthalmoplegia has been reported in patients with headaches with neurologic deficits, and cerebrospinal fluid (CSF) lymphocytosis (HaNDL) syndrome (known as pseudomigraine syndrome with CSF pleocytosis) [29,30]. This condition is a monophasic benign selflimited syndrome characterized by headaches, transient neurologic symptoms, and the presence of aseptic CSF lymphocytic pleocytosis. Pituitary apoplexy is not an uncommon clinical syndrome characterized by abrupt onset of severe headache, vomiting, visual impairment, ophthalmoplegia, meningismus, altered level of consciousness, and endocrine dysfunction. It occurs as a complication of sudden hemorrhage or infarction of the pituitary gland, generally within a pituitary adenoma [31]. Treatment with corticosteroids should be initiated as soon as possible, and decompressive

4 4 Ocular manifestations of systemic disease surgery should be considered in patients with decreased visual acuity or visual field defect. Paratrigeminal oculosympathetic syndrome (Raeder s paratrigeminal neuralgia) is an uncommon benign neurologic disorder characterized by unilateral periocular pain and ipsilateral postganglionic Horner s secondary to involvement of the oculosympathetic fibers along the course of the internal carotid artery [32,33]. Idiopathic lesions of the middle cranial fossa should be excluded [34]. Headaches, Horner s syndrome, and painful ophthalmoplegia may also be seen in the setting of cavernous sinus thrombosis or aneurysm, carotid dissection, and parasellar neoplasms, and infectious causes such as mucormycosis, rhizopus, and herpes zoster ophthalmicus. Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure and the absence of structural causes such as space-occupying lesion, ventriculomegaly, dural venous sinus thrombosis or meningeal process. It is more common in overweight young women during their reproductive years. Headache is the most prominent clinical feature and is present in over 90% of patients with IIH, followed by visual loss, blurred vision, and diplopia secondary to abducens nerve palsy. The headache is chronic, diffuse, nonspecific in characteristic, worse in the morning, usually exacerbated by coughing, bending, sneezing, or by the valsalva maneuver [35 39]. The presence of papilledema requires prompt diagnosis and immediate intervention to prevent visual loss. MRI and MR venogram should be obtained to exclude secondary causes of papilledema. An increased opening CSF pressure with normal fluid analysis is diagnostic. Management includes strict weight loss, acetazolamide, and diuretics. Surgical intervention with optic nerve sheath fenestration and CSF diversion procedures should be considered in patients with rapid visual loss and refractory headaches. Acute optic neuritis is an inflammatory condition characterized by monocular visual loss and decreased color vision with pain on eye movements. Traction of the inflamed optic nerve sheath at the orbital apex is thought to be the causative factor in pain generation on eye movements [40,41]. Other causes of optic neuritis such as infectious inflammatory conditions, connective tissue, and ischemic disorders are usually painless [42]. High doses of intravenous steroids are proven to hasten the recovery process [41]. Anterior ischemic optic neuropathy (AION) is a common cause of visual loss in giant cell arthritis (GCA), a systemic vasculitis of the median and large arteries affecting patients in the fifth and sixth decades of age [43,44]. Symptoms include constant nonspecific nagging holocephalic headache, jaw claudication, malaise, and weight loss. The visual loss is usually painless and is due to ischemia of the short posterior ciliary arteries. Other ocular symptoms include ophthalmoplegia, monocular blindness, central retinal artery and cilioretinal artery occlusion [45]. Conclusion Headaches associated with visual disturbances are often due to underlying neurological conditions. Migraine and its variants are the most common primary headache disorder associated with ophthalmological symptoms, followed by TACs and hemicrania continua. Many secondary headache disorders are associated with a wide spectrum of ocular manifestations including true papilledema, ophthalmoplegia, and Horner s syndrome. Familiarization with both primary and secondary headache disorders is the key for accurate diagnosis and management. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp ). 1 The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004; 24 (Suppl 1): Lipton RB, Bigal ME. Migraine: epidemiology, impact, and risk factors for progression. Headache 2005; 45 (Suppl 1):S3 S13. 3 Evans RW, Grosberg BM. Retinal migraine: migraine associated with monocular visual symptoms. Headache 2008; 48: Pradhan S, Chung SM. Retinal, ophthalmic, or ocular migraine. Curr Neurol Neurosci Rep 2004; 4: Grosberg BM, Solomon S, Friedman DI, Lipton RB. Retinal migraine reappraised. Cephalalgia 2006; 26: Grosberg BM, Solomon S, Lipton RB. Retinal migraine. Curr Pain Headache Rep 2005; 9: Kaniecki RG. Basilar-type migraine. 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