however, isolated and localized occipital or temporal lobe seizures may produce visual hallucinations as their only manifestation.

Release hallucinations often occur in patients with decreased vision or visual field defects.254 They may also occur in the setting of monocular or binocular visual loss or homonymous hemianopia and may manifest in patients with relatively mild visual loss.60,254 These hallucinations range from unformed phosphenes to formed hallucinations with complex patterns. Release hallucinations presumably occur when normal visual impulses are removed, releasing indigenous cerebral activity within the visual system.60 They tend to be continuous and can last from minutes to days, in contradistinction to irritative hallucinations, which last from seconds to a few minutes.60 Release hallucinations are neither associated with electroencephalographic abnormalities nor altered by anticonvulsant therapy.

The failure to clearly distinguish the irritative from the release type of hallucination has led to considerable confusion regarding their localizing value. The concept that hallucinations of occipital origin comprise unformed phosphenes applies only to the irritative variety. Unlike irritative hallucinations, which vary in character depending on their site of origin, release hallucinations have no localizing value and can follow injury to the visual system anywhere from the eye to the occipital cortex.60,225,412 For example, formed release hallucinations occasionally occur in adults with dense cataracts or macular degeneration.244 Children can experience “phantom vision” following enucleation of one or both eyes.61 Patients with visual loss frequently acknowledge experiencing both formed and unformed visual hallucinations when specifically asked.

The aura may occur prior to, concurrently, or even after the onset of the headache.

The diagnosis of pediatric migraine is established on the basis of the personal profile, attack profile, and family history, as well as the absence of physical findings. In the child with transient visual disturbances or unexplained headache, the personal history provides important clues to the diagnosis of migraine.65 Pediatric migraineurs often have a history of migraine equivalents, including colic, recurrent abdominal pain, cyclic vomiting, pavor nocturnus (night terrors), paroxysmal vertigo, and paroxysmal torticollis in the first few years of life.26,27,49,125

Some children stop playing with their friends, watching television, or using the computer. Even between attacks, migraineurs often describe themselves as very reactive to extraneous visual, auditory, olfactory, gustatory, and thermal stimuli.14,86–88,137 Bright lights (sunlight reflecting from snow or water) or strong smells (e.g., perfume, gasoline) can precipitate a migraine.80,85,87 A history of motion sickness is also strongly associated with migraine and considered to be an associated feature of the migraine diathesis.14,24,86–88 In attempting to elicit a family history of migraine, it is useful to ask whether any of the firstdegree relatives have “sick headaches” or have ever had to go into a dark room, put a damp rag on their head, and go to sleep because of a severe headache. Features of the attack history include the presence or absence of an aura, the characteristics of the headache, and the presence or absence of additional neurological impairment. The prevalence of migraine is approximately equal in boys and girls younger than 7 years of age. A female predominance of 3:2 is present from 7 years of age until puberty. After puberty, the relative prevalence becomes further skewed toward girls.36

Transient Visual Loss

Migraine

Migraine is not just a headache49 but an episodic brain disorder that affects approximately 15% of the population.240 Migraine can cause transient sensory, autonomic, motor, visual, and cognitive impairment. Although headache is a prominent feature of migraine, it is not invariably present.49 Many migraine attacks begin slowly and evolve through sequential stages of neurological dysfunction. Selby357 described migraine as a “drama in three acts,” comprising premonitory symptoms (frequently not recognized) and aura, a headache phase, and a post-headache phase. Premonitory symptoms, which precede the aura, include mood changes, irritability, fluid retention, increased thirst, and frequent urination, food cravings, and increases or decreases in energy levels.11

Migraine Aura

Although migraine headache is less prevalent in children than in adults, the presenting complaint of transient visual disturbances results in the diagnosis of migraine with considerable frequency in the pediatric age group.36,58,100 The stereotypical visual migraine aura lasts 25–30 min but occasionally may subside in a few minutes or last several hours. The variability in the characteristics and the frequency of migraine aura so common in adults is even greater in children. The examiner must be aware not only of the classic adult migraine aura but also of the variations on this theme that are presented in the pediatric age group.10,108,176

Some children are able to describe the classical form of scintillating scotoma with expansion or buildup of the fortification figure (Fig. 5.1). The visual disturbance typically begins as a fog, loss of illumination, central flashbulb, or brightness pericentrally in one hemifield, progressing in a

few seconds or minutes to a few degrees of central scotoma lined on the temporal side by a luminous zigzag line, or teichopsia (Greek word meaning fortification-seeing). The jagged lines of the fortification specter may be colored or gray and appear to vary in brightness in a way that is often described as flashing, jabbing, boiling, or rolling217 (Figs. 5.1 and 5.2). The visual disturbance expands in the shape of a horseshoe with a centrally directed open end encompassing a negative scotoma.176

Fig. 5.1  Fortified Italian City of Palmanova, Italy. Courtesy of James J. Corbett, M.D.

This sensation usually begins as a small pericentral disturbance encompassing only a few degrees, and gradually expands toward the temporal periphery over 20–30 min to involve a large portion of the hemifield of both eyes (although patients frequently interpret the visual disturbance as monocular). As the fortification scotoma expands peripherally, it erases the visual field to produce a transient homonymous scotoma. Fortification scotomas are seen with the eyes open or closed and are even perceived in patients with no eyes. This hemifield scotoma frequently precedes the characteristic headache of migraine, but it may also occur alone in the absence of a headache, in which case it is termed an acephalgic migraine.290

In addition to the typical fortification scotoma, the range of visual disturbances in adult migraine is quite broad and includes positive and negative scotomas,108 blurred vision, foggy vision, flickering lights, colored lights, zigzag lines, and a heat wave sensation, all presumably of occipital origin. Children with migraines are more likely than adults to describe a variety of visual disturbances other than the classic fortification scotoma.65 The descriptions provided by children tend to be more picturesque, such as “a star breaking into a million pieces,” “heat waves,” “water coming down a window,” “lines coming down from the sky like it’s raining,” “like looking through cellophane,” “sparkles,” “dancing lights,” or “dots and blobs” that gradually enlarge to obliterate the visual field.152,299

Migraine with aura (classic migraine) is preceded by or accompanied by a focal disturbance of cerebral or brainstem function.49 The migraine aura may also be nonvisual. Some patients experience a sensory aura consisting of migratory paresthesias of the tongue, lips, and hand (cheiro-oral

migraine). Transient language disturbance, including mild aphasia, may occur as part of the aura phenomenon. Common migraine may not have a clearly defined visual or sensory prodrome, but autonomic premonitory symptoms may occur, including yawning, hunger, thirst, irritability, edema, euphoria, or depression. The premonitory mood changes and skin pallor, which are often noted by parents prior to the onset of childhood migraine, may be manifestations of the same autonomic symptomatology.280 Benign paroxysmal childhood vertigo can precede by months or years migrainous vertigo symptoms in affected patients.305 Mothers learn to recognize their child’s migraine attack prior to the onset of headache by observing skin pallor and “goose bumps,” with cold, clammy perspiration, and cold extremities.49 Some children develop periorbital discoloration during or just before a migraine.365

Amaurosis Fugax as a Migraine Equivalent

The old term amaurosis fugax is somewhat arbitrarily applied to transient monocular visual loss of relatively rapid onset and fairly rapid resolution. The episodes characteristically last 2–10 min and are unaccompanied by significant pain. In adults older than 50 years of age, the term amaurosis fugax has come to signify transient visual loss associated with ipsilateral carotid atherosclerosis. The characteristics and duration of transient visual loss have therefore become the critical historical determinants in distinguishing retinal embolization from migrainous visual loss in older adults. In young adults or children, however, migraine is a common association with amaurosis fugax. Tomsak and Jergens388 described 24 adults with benign recurrent transient monocular blindness that was presumed to be migrainous in etiology. The visual loss was predominantly one-sided and stereotyped in character, although symptoms varied greatly from patient to patient. Postural change or exercise was a provocative factor in half of the cases. Other neurological symptoms were not present, and only one patient developed permanent visual loss during an attack. Evaluation by computed tomography (CT) scanning, cerebral angiography, echocardiography, and ophthalmodynamometry, when performed, were uniformly normal.

Tippin et al386 reported similar findings in a group of adolescents and young adults with amaurosis fugax. They found that headache or orbital pain accompanied the amaurotic spells in 41% of cases and that an additional 25.3% had severe headaches independent of the visual loss. None of the 11 patients who had angiography had an atherosclerotic lesion of the carotid artery. None of the patients who were reexamined after an average follow-up of 5.8 years have had a stroke. The authors concluded that amaurosis fugax is associated with a more benign clinical course in young patients and that migraine is a likely cause for the visual episodes. They advised that carotid angiography and invasive diagnos-

tic studies are unwarranted in young patients with transient visual loss and who are otherwise healthy because significant and/or systemic diseases are rarely discovered.

O’Sullivan et al299 found a personal or family history of migraine in 8 of 9 children and young adults with transient monocular visual loss. They noted that, as with migraines, the episodes of visual loss tended to occur in clusters. Investigation revealed no embolic or atheromatous etiology. Appleton et al16 also attributed atypical forms of transient visual loss in children with acephalgic migraine and found that it carries a benign prognosis in young patients. While the term migraine is reassuring to parents and useful to clinicians in connoting a benign prognosis in children with transient monocular visual loss, little is known about the underlying pathophysiology or the site (retinal neurons, retinal vessels, optic disc) of dysfunction.

Migraine Versus Retinal Vasospasm

The term vasospasm is often postulated as the mechanism of migrainous transient monocular visual disturbances in both children and adults.185 The notion that retinal vasospasm can be ascribed to migraine derives from the long-supplanted concept of migraine as a vasospastic process.220 However, retinal vasospasm may occur as an independent event or as a component of migraine. As discussed below, the hemodynamic changes that occur with migraine are not due to vasospasm but rather due to changes in neuronal activity with vasoneural coupling.128 While retinal vasospasm may occur idiopathically, affected individuals often have medical histories that are significant for Raynaud’s phenomenon, systemic lupus erythematosus, hypercoagulability, autoimmune diseases, and atherosclerosis. Retinal vasospasm may therefore be precipitated by a number of factors, including migraine headache or its pharmacological treatment with vasoconstrictors.

Isolated retinal vasospasm has been described, visualized, and photographed in fewer than ten adult patients.31,45, During these attacks, the retina appears pale, the arterioles are narrowed, there are focal arteriolar con-

strictions, the veins are narrowed, and fluorescein angiography shows delayed filling. The retinal veins appear to dilate dramatically as the attack abates. Similar arterial vasospasm may affect other tissues in the same patients (e.g., Raynaud’s phenomenon, Prinzmetal angina). The clinical course is generally benign, but optic nerve or retinal infarction has been documented as an uncommon consequence of retinal vasospasm.176

It has recently been argued that retinal vasoconstriction is a more likely mechanism than retinal migraine for transient monocular visual loss. A large review of previously reported cases found definite migraine, as defined by

International Headache Society (IHS) criteria, to be an exceedingly rare cause of transient monocular visual loss. With one possible exception, there have been no convincing reports of permanent monocular visual loss associated with migraine. Thus, the diagnosis of retinal migraine remains one of exclusion. Spreading depression has been observed in vitro in the avascular retinas of frogs and chicks,398,399 but has never been seen in vascularized mammalian retinas.167,261 Moreover, no clinical correlation has been made between retinal spreading depression and monocular visual loss.167,426 However, it remains entirely possible that these cases may result from transient neuronal inhibition or depression at the retinal level rather than focal ischemia related to vasoconstriction, and that such cases will eventually be classified as migraine equivalents.

Migraine Headache

Migraine headache in adults may be hemicranial or holocranial, bifrontal, or frontal in distribution. Unilateral headache is seen in both common and classic migraine. Migraine headache has a gradual onset and builds in intensity over minutes or hours. It can last a few hours to several days.49 It is described as a dull headache if the pain is not severe, but it becomes throbbing or pulsatile as the pain increases, although the character of the headache in children differs somewhat from that in adults, so that a minority of children describe their headache as throbbing.280 Even in the absence of the classic visual aura, some adults report short-lived phosphenes.62 The duration of migraine headache is shorter in children, typically lasting 1–2 h, compared with a 4-h minimum for adults.2,3 Complaints of bifrontal or bitemporal headaches or central forehead pain are more common in children, and unilaterality is uncommon.280 Head trauma may be a significant triggering factor. Migraine headache is often associated with nausea, vomiting, or diarrhea, and children are often photophobic and phonophobic during the attack.18,280 The pain is relieved by vomiting or sleep. In attempting to determine whether headaches are migrainous, we ask the patient what they do when they get an attack. They often give a stereotypical reply such as “I go in my room, close the door, turn off the lights, pull down the shades, pull the covers over my head, and go to sleep.”

Migraineurs may also describe jabs of pain in the scalp or eye when they are not having headaches, as well as during a migraine attack.49 These have been termed “ice-pick headaches” or “the syndrome of jabs and stabs.”329 They may be isolated or occur repetitively over a day or two. Those involving the eye are known as ophthalmodynia fugax.47

The diagnosis of migraine in an infant or toddler is often made only in retrospect, when the child is older and clear symptoms of pediatric migraine become evident. Barlow

found the most common migraine manifestations in the first years of life to be repeated vomiting followed by a behavioral change (i.e., irritability or lethargy), vertigo, ataxia, or pallor, and sleep relief.26,63 Many of these children were also able to communicate that they had a headache either verbally or by holding their head. Headaches that interrupt play are also an important clue to the diagnosis of migraine.

Contrary to the notion that migraine aura activates trigeminal afferents, thus causing the pain and cascade of events that we recognize as migraine, Goadsby and colleagues have argued that migraine aura is a parallel process to the pain.128,133 According to this hypothesis, the aura is triggered or facilitated by the same hyperexcitability that is responsible for the pain, and other symptoms and process that resides in, and is governed by the brain. These investigators believe that migraine pain may have more to do with abnormal perception of the normal sensory input than activation in the nociceptive pathways in the classical way that pain is generated. About two-thirds of patients with migraine complain of allodynia (pain from nonnoxious stimuli).357 In this context, the characteristic photophobia and phonophobia are normal light and sound sensation that become exaggerated or amplified by the migrainous brain.133

Complicated Migraine

Complicated migraine syndromes are more common in children and adolescents than in adults. Many systemic diseases including episodic ataxia type 2, MELAS, and ornithine transcarbamylase (OTC) deficiency may present with complicated migraines. For example, the finding of a micronystagmus with upbeat or downbeat nystagmus during a migraine, which is brought on by hunger, alcohol, anxiety, or fatigue, should suggest the diagnosis of episodic ataxia type 2.374 The MELAS syndrome may underlie the “malignant migraine syndrome,” in which children with complicated migraine headaches develop intractable seizures and large alternating occipital infarcts.58 OTC deficiency is a urea-cycle disorder caused by a mutation in the enzyme that converts ornithine to citrulline.374 This x-linked mutation decreases the efficiency of the urea cycle, causing an accumulation of ammonia. Affected males present as newborns and heterozygous females present later in life. The presenting signs of OTC deficiency are largely due to cerebral edema caused by elevated levels of ammonia. They include seizures, chronic vomiting, developmental delay, ataxia, headache, lethargy and cortical visual loss.434 Children with this disorder often have a history of protein aversion and frequent migraines.355

Acute confusional migraine was first reported by Gascon and Barlow116 in four children ages 8–16. It resembles acute toxic psychosis and usually presents as one of the first episodes of migraine in a child.116 During an attack, the

child may display confusion, agitation, an altered sensorium, or withdrawn, noncommunicative behavior. The attack usually ends with a period of prolonged sleep. Recurrent 30to 60-min episodes of confusion or even psychotic behavior in children should lead one to consider the diagnosis of migraine. These attacks eventually evolve into more typical migraine episodes.98

Acute hemiplegic migraine may occur as a manifestation of complicated migraine as a familial or sporadic disorder.57,127,129,385 Familial hemiplegic migraine is characterized by attacks of hemiplegia and hemianesthesia that begin in childhood and may last several days.57 Recurrent episodes may vary from side to side and may be associated with hallucinations, aphasia, or confusion. The gene for familial hemiplegic migraine has been mapped to chromosome 19.184 Triptans are contraindicated in the treatment of this form of migraine.

Alternating hemiplegia of childhood is a rare disorder characterized by paroxysmal spastic or dystonic attacks affecting one side of the body, with onset prior to 4 months of age.7,97,333 It is associated with tonic or dystonic attacks, abnormal ocular movements (monocular pendular nystagmus, episodic deviations of the ipsilateral eye),97 and autonomic abnormalities (focal blanching of a limb or whole side of the body), which may usher in an attack.97,333 Its onset is usually before 18 months of age, and its clinical course is progressive, with patients developing fixed neurologic deficits including choreoathetosis, dystonia, ataxia, and neurodevelopmental disturbances.333 Many patients have associated motion sickness.68 Seizures are reported in a subset of patients.7,97,112,330 Although familial cases have been reported,187,272 the disorder is usually isolated.

Benign paroxysmal vertigo of childhood is the most common cause of vertigo in children without any detectable ear disease or hearing loss.393 This condition was originally described as a typical vestibular attack including nystagmus, nausea, vomiting, and diaphoresis.27 The only objective evidence of vestibular system dysfunction is the presence of nystagmus during the attack.271 The age of occurrence is usually 1–5 years.6 Many patients have associated motion sickness and go on to have other migraine symptoms,393 suggesting that benign paroxysmal vertigo of childhood is a precursor of migrainous vertigo (alias, basilar artery migraine. See below).49 Benign paroxysmal childhood vertigo often precedes the onset of migrainous vertigo symptoms by months or years.305

Most patients show mild central ocular motor signs such as saccadic pursuit, spontaneous or gaze-evoked nystagmus, and positional nystagmus in the symptom-free interval, suggesting migraine. Benign paroxysmal torticollis of infancy may be another forerunner to migrainous vertigo,271,347 as its benign course and close association with migraine resembles benign paroxysmal vertigo of childhood.125

Bickerstaff33 first described symptoms of basilar artery migraine as referable to the very diffuse circulation territory of the basilar artery involving virtually all structures in the posterior fossa and brainstem. Because basilar migraine has symptoms that are neither limited to the basilar artery territory nor with evidence that the basilar artery is involved in its pathophysiology, it is now termed basilar type migraine, emphasizing that is it not a primary vascular event.129 Rather, it probably results from a regional hyperexcitability, with a similar vasoneural coupling to that seen in cortical sprea­ ding depression. This type of migraine is more common in adolescents.

In one study,249 5% of children with migraine in an outpatient clinic were diagnosed with this form of complicated migraine. Symptomatology is progressive during an attack, with each attack lasting 2–45 min. Visual loss is often the initial event, with a disturbance of central vision, which is often described as resembling a bright sun or flashbulb.49 This visual disturbance may evolve into a total loss of vision or large blotches of positive visual scotomas obscuring both hemifields. The visual loss is then followed by some combination of vertigo, ataxia, dysarthria, tinnitus and, occasionally, tingling of the hands and feet.

Other symptoms of basilar type migraine include alteration or loss of consciousness, and hyperacuisis. Headache may be absent, but when it occurs, it is frequently occipital and throbbing. Abrupt loss of consciousness, lasting for a few minutes, can also occur.171,216 Most children also have common or classic migraine attacks, and symptoms of basilar type migraine gradually become less frequent and eventually stop altogether. Basilar type migraine must be distinguished from benign childhood epilepsy with occipital paroxysms (discussed later). Triptans are contraindicated in the treatment of basilar type migraine (IHS criteria).

Acute migrainous vertigo is an important cause of episodic dizziness in children. The topic of migrainous vertigo encompasses an evolving classification system in which the terms paroxysmal torticollis of infancy, benign paroxysmal vertigo of childhood, migrainous vertigo, and basilar artery migraine are used to describe what are probably different expressions of the same disease as a function of age.68

Its pathophysiology can involve both central and peripheral vestibular dysfunction,406 which has shown to be linked to CACNA1A mutation.125 The differential diagnosis of migrainous vertigo includes the channelopathy episodic ataxia type 2,374 which also exhibits interictal nystagmus and saccadic pursuit,113 as well as neurometabolic disorders such as MELAS and OTC deficiency, and temporal lobe epilepsy.

Disturbances of higher cortical function have also been described with pediatric migraine.65,208,290 In older children, these disorders include disturbances of color vision (central achromatopsia), abnormal facial recognition (prosopagnosia),