45 have been used in an emergency department setting for the treatment of acute headache. For adolescents older than 12 years of age, sumatriptan nasal spray is effective and should be considered for the acute treatment of migraine.231 For preventative therapy, flunarizine is probably effective and can be considered, but it is not available in the United States.231

Migraine headaches that are frequent or severe enough to require prophylactic therapy are relatively uncommon in childhood.281 Only 18% of children younger than 8 years of age with migraine have more than one attack per month.281 Prophylactic therapy is warranted when the child has frequent headaches (more than four per month) or if the headaches are infrequent but severe, or if the child fails to respond to abortive therapy. Most medications used for adult migraine prophylaxis have been used in pediatrics; some have clinical studies to support their use, while others are used on the basis of clinical experience. Some studies have shown propranolol and anticonvulsants to be effective in the treatment of migraine in children;18,117,247 however, other studies have questioned these results.111,296 In our experience, these medications frequently have side effects (e.g., lethargy, tiredness, apathy, memory problems), and we use them infrequently. Periactin (cyproheptadine) is an effective prophylactic medication, but it causes drowsiness and weight gain.

In our experience, the most effective prophylactic medications are the tricyclic antidepressants or beta blockers as first-line treatments, calcium channel blockers as second-line treatment, and the anticonvulsant topiramate as a thirdline treatment.231 Amitriptyline appears to be a safe and effective prophylactic medication. It has been proven effective in the treatment of both migraine and tension-type headaches in adults and appears to be equally safe and effective in children when used at lower doses than those used to treat depression. For this reason, the prophylactic effect of amitriptyline against migraine is believed to be independent of its antidepressant effect. Once-a-day dosing (bedtime), relatively infrequent side effects (transient daytime sedation), and improvement in sleep patterns make it attractive to use in children.

Children younger than 5 years of age are usually given 10 mg as a starting dose, while older children are started at 25 mg. This dose can be gradually increased at 3- to 4-week intervals, with a maximum dose that rarely exceeds 75 mg a day. A baseline electrocardiogram (EKG) should be obtained prior to starting any tricyclic antidepressant to look for a prolonged PR interval (greater than 0.20 ms) or a corrected QT interval (greater than 0.45 ms). A follow-up EKG should be obtained once a therapeutic level has been reached. Beta blockers can be prescribed as propanolol, 1 mg/kg/day, or atenolol, 25 mg/day.

If the headache is exclusively migrainous, with no other headache (e.g., tension headache) occurring at regular inter-

vals, we also consider verapamil a safe and effective prophylactic medication.15 The starting dose is generally 20 mg three times a day in younger children and 40 mg three times a day in older children. This dosage can gradually be increased, with the final daily dosage rarely exceeding 240 mg. Side effects are few, with constipation being the most common. Treatment for 2–6 months is usually recommended before the child is weaned from the medication. Topiramate (76 mg/ day) has found application in pediatric migraine prophylaxis, but some patients report side effects including sedation, cognitive slowing, loss of appetite, and weight loss.105,232,439 Pediatric dosing starts at 25 mg at bedtime and increases to 50–100 mg at bedtime.

Many children, at some point, require reinstitution of a prophylactic medication if the headaches become frequent again. Nonpharmacologic therapy, including sleep regulation, avoidance of dietary triggers, and stress management, can be incorporated into the treatment plan.89,232 Relaxation techniques and biofeedback have been found to have both shortand long-term benefits in migraine.89 The concentration and effort required to learn these techniques limit their usefulness in children, but these techniques should be considered in children who seem intractable to other therapy. In our experience, some children with migraine and moderate amounts of hyperopia show a dimunition of frequency with glasses to correct most of their hyperopic refraction. In this setting, the work of constant focusing may precipitate migraines in the child who has an inherent predisposition. Tinted lenses can be prescribed when photophobia is problematic. In adults, botulinum toxin injected into the frontal region works by being a synaptic poison for cGRP, which may be a local mediator for pain in the trigeminal system. In the future, cGRP antagonists will undoubtedly find application in the treatment of migraine. MR stimulation has been reported to prevent headaches when administered during the aura.

Epilepsy

Epileptiform Visual Symptoms with Seizure Aura

In 1879, Gowers140 described a patient with epilepsy who had “epileptoid attacks with visual aura.” The patient described episodes of having a very brilliant image before him “as if he had a polished plate on his breast” or “a flickering light, like a gold serpent.” Gowers then examined the records of a thousand of his personal patients with epilepsy and found 84 who exhibited a visual aura.140 Holmes172 expanded on the findings of Gowers in his classic studies of gunshot wounds to the occipital region and elaborated on elementary visual hallucinations and temporary blindness as features of epilepsy in these patients. Penfield and Erickson309 reported the ability to

reproduce the visual aura by cortical stimulation of the occipital lobe at the time of surgery. Since that time, elementary visual hallucinations have been reported as the most common symptom of occipital lobe epilepsy.248,345,424,425

Children with a seizure focus may have irritative visual hallucinations associated with a purely focal seizure in which the visual hallucinations are associated with only minimal alterations in consciousness or with a more dramatic seizure with secondary generalization. The degree of organization of the visual hallucinations or images reflects the anatomical area of the visual sensory system that is involved in the abnormal discharge. The most complex visual scenes are produced by seizure discharge in the temporal lobe, which may take the form of vivid and detailed scenes containing recognizable human and animal forms that move and interact. Some children report autoscopic phenomena (visual reproductions of the self or parts of the body in external space) as part of a temporal lobe aura.419 Focal seizures in visual association areas may also produce complex imagery, including geometric shapes, such as squares and triangles, or simple animal forms.

Occipital lobe seizure foci are more common in children than in adults.402 Generalized seizures may or may not emanate from an occipital focus. When they do, epileptic photopsias last only seconds or, rarely, minutes before the onset of a seizure.212 Patients with photosensitive epilepsy are reported to have deficient cortical mechanisms for contrast gain control for pattern stimuli of low temporal frequency and high luminance, which may explain why television and video games can be powerful triggers of visually induced epileptic seizures.317

Seizures in area 17 (occipital pole) are elementary, lacking form, depth, movement, whereas those originating more anteriorly, in visual association areas (areas 18 and 19) are more elaborate, with form, color, depth, movement. A focal seizure in the occipital cortex produces the simplest form of epileptic visual image, consisting of multicolored hallucinations with circular or spherical patterns contralateral to the focus.303 Seizures that also affect the posterior temporal neocortex are the most complex, representing people and formed objects in the environment. The laterality of the seizure focus can often be inferred from the clinical signs and symptoms. Conjugate eye deviation that occurs at the onset of a clinical seizure is highly suggestive of an occipital focus contralateral to the direction of eye deviation, especially if visual auras are also present. The hallucination also tends to occupy the visual hemifield contralateral to the seizure focus. Some patients also report an unusual sensation that their eyes are moving.173

In a review of 42 patients with medically refractory occipital lobe epilepsy, 29% of the patients described blacking out of the vision, sometimes lasting for several minutes. In many of these patients, no other manifestation of seizure activity

occurred.345 Visual hallucinations, usually described as flashing, colored lights, stars, wheels, or triangles, were commonly reported. Only a small number of patients had formed visual hallucinations and, of these patients, all had right-sided occipital lesions. In this series, 46% became seizure-free, and 21% had a significant reduction in seizure frequency following surgical excision of the epileptic focus. Ludwig and Marsan248 found simple visual aura to be the most prevalent subjective sensory experience (47%) among 55 epileptic patients with EEG evidence of exclusively or predominantly occipital involvement.444

Visual field defects are found in 20% of epileptic patients with EEG evidence of occipital foci.248 Other estimates of the overall incidence of visual disturbances in epilepsy have ranged from 4% to 10%.124,310 Visual aura was most common when patients were selected according to the criterion of occipital epileptiform involvement.444 Hallucinations associated with seizures can be either ictal or part of a postictal cortical release phenomenon, and their clinical features may help distinguish their etiology.183

Occipital lobe epilepsy has been divided into benign and symptomatic categories. Benign occipital epilepsy (BOE) in childhood is further subdivided into two disorders. The first is early-onset Panayiotopoulos syndrome, which presents in early childhood with predominantly nocturnal spells of tonic eye deviation, nausea, vomiting, clonic activity, and possibly other autonomic manifestations.

Ictal visual symptoms occur in only 10% of patients and consist of elementary or complex visual hallucinations, illusions, blurring, or blindness. Long-term outcome is excellent, and seizures remit with age. The second is Gastaut syndrome, which presents in later childhood with diurnal, brief visual seizures consisting of elementary visual hallucinations and, possibly, sensory illusions of ocular movement and tonic eye deviation. Postictal headache is common. This form can be mimicked by other symptomatic etiologies of occipital lobe epilepsy. Common causes of symptomatic occipital epilepsy in children include Sturge-Weber syndrome, cortical dysplasia, neonatal hypoglycemia, celiac disease, MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes), traumatic brain injury, gliotic or inflammatory scarring of brain tissue, porencephalic cysts, glial tumors, and angiomatous lesions). It tends to be more refractory to medical treatment, and the prognosis is less clear than with Panayiotopoulos syndrome.248

Mitochondrial disease due to mutations in the POLG1 gene can cause an epileptoic syndrome with initial features of occipital lobe epilepsy.102,211 Occipital seizure phenomena include flickering colored light (sometimes persisting for weeks, months, or even years), ictal visual loss, horizontal or vertical nystagmus, dysmorphopsia, micropsia, macropsia, and palinopsia. In one study,102 age at presentation ranged

from 6 to 58 years, with a mean age at presentation of 18.4 years (6–58 years). Most patients develop simple partial seizure phenomena with motor symptoms, suggesting frontal lobe seizure initiation or spread. All patients develop status epilepticus, often leading to death.102 In other familial types of epilepsy, mutations may be found, and epilepsy susceptibility genes continue to be identified.211

Celiac disease is increasingly recognized as a multisystem disorder that can cause visual disturbances secondary to occipital lobe epilepsy in both children and adults. CT scanning shows bilateral cortical calcification of the occipitoparietal regions, while MR imaging shows low-signal areas on axial T2-weighted sequences corresponding to these calcifications. Seizure types include simple partial, complexpartial, and secondarily generalized seizures. The seizure semiology may include blurred vision, loss of focus, seeing colored dots, and brief stereotyped complex visual hallucinations, such as seeing unfamiliar faces or scenes.314

Ictal Cortical Blindness

Because occipital epileptiform activity is most common in children, ictal cortical blindness should be considered in the differential diagnosis of intermittent cortical blindness in children.444 Children with epilepsy limited to the occipital lobe may have acute cortical blindness as the major manifestation of the seizure.444 Most reports describe cases in which amaurosis was the sole presentation of epileptic activity (i.e., an “ictal equivalent”) or cases in which epileptiform activity was documented by EEG during the amaurotic episode. Due to the inherent difficulty involved in obtaining an EEG during these brief attacks (unless they occur frequently), the diagnosis is often made presumptively on the basis of the presence of interictal occipital epileptiform activity.

Strauss373 described an 11-year-old boy who suffered from attacks of complete blindness lasting 2–10 min, with preservation of consciousness. The postictal EEG showed bioccipital epileptic activity, with similar and often simultaneous activity in the temporal lobes. Zung and Margalith444 described a 7-year-old boy who experienced several episodes of complete visual loss, accompanied by gastrointestinal symptoms and a sensation of fright, but with preservation of consciousness. These episodes ended abruptly with visual recovery and no postictal phenomena. CT scanning was normal, and interictal EEG showed bioccipital epileptiform activity.

Postictal Blindness

Cortical blindness is a rare but well-recognized manifestation of epilepsy. Children seem to have transient visual loss following seizures more often than adults.204,342 Similar to the

weakness of Todd’s paralysis, postictal blindness is usually temporary, but cases of permanent visual loss have been described.9,203,340 These episodes of permanent visual loss have occurred in patients with preexisting visual abnormalities.307 Harris160 reported several cases of hemianopia following unilateral convulsions. Postictal blindness may range in duration from minutes to days, and in rare cases, it may last several weeks.204 The mechanisms of postictal visual loss are poorly understood.

Permanent neurological damage following seizures has usually been attributed to the effects of hypotension, ischemia, acidosis, and hypoxia. Permanent blindness following generalized seizures has been likewise attributed to the effects of poor oxygenation.342 However, primate studies have demonstrated that prolonged seizure activity can produce neuronal damage without hypotension, acidosis, or hypoxia.268 It may be that prolonged seizure activity can directly injure the visual cortex and thereby lead to permanent visual loss.

Distinguishing Epilepsy from Migraine

There is considerable overlap in the symptoms produced by epilepsy and migraine in children.25 Both disorders are episodic, with sudden onset and recovery. Both may have visual loss or hallucinations, are frequently associated with headache and behavioral changes, and are associated with neuronal hyperexcitability. There is an increased incidence of epilepsy among migraineurs and of migraine among epileptics. Although headaches associated with seizures are usually postictal, ictal headaches may, occasionally, be the sole expression of a seizure in the limbic system and/or other parts of the cortex. The utility of EEG in distinguishing epilepsy from migraine is unfortunately limited, because EEG abnormalities, including focal epileptiform changes, have been reported in up to 74% of children with migraine who never develop clinical epilepsy.25

The neurological features that can be used to differentiate migraine from epilepsy are summarized in Table 5.1. The major differentiating feature is that consciousness may be lost or substantially altered during a seizure, and the transition is relatively abrupt. The most common phenomenon in a complex partial seizure is progression to a state of altered consciousness, with an appearance of confusion and bewilderment accompanied by unresponsiveness. This is frequently the result of spread of the ictal discharge into the temporal lobe following occipital origination. Progression to loss of consciousness or secondary generalization with the production of a convulsive seizure may also occur. Loss of consciousness does not occur in most forms of migraine, but it may occur in basilar type migraine.33

EEG, electroencephalogram

Adapted, with permission, from Hanson158

The characteristics of the visual hallucinations and their temporal relationship to other symptoms are also useful in distinguishing epilepsy from migraine. The visual hallucinations of migraine are usually present longer (20–30 min) than the visual aura of a seizure (seconds to a few minutes). Occipital lobe seizures tend to occur daily, whereas migraine-associated hallucinations tend to occur with longer time intervals (weeks to months).288 However, occipital lobe seizures can be followed by a headache that is indistinguishable from migraine.288

Panayiotopoulos303 compared elementary visual hallucinations in 50 patients with migraine and 20 patients with occipital epileptic seizures. He found that epileptic seizures are predominantly multicolored, with circular or spherical patterns, as opposed to the predominantly black and white linear patterns of migraine. Elementary visual hallucinations, particularly when combined with headache, vomiting, or blindness, are more likely to be diagnosed as characteristic of migraine despite the fact that they are also common ictal manifestations of occipital lobe seizures.303 Other major points of differentiation between epilepsy and migraine are summarized in Table 5.2.

The distinction between migraine and epilepsy becomes critical in the child with photopsias and headaches who harbors an occipital arteriovenous malformation (AVM). In the absence of other clinical evidence of seizure activity, the character of the photopsias and their temporal relationship to the headache can often provide a historical clue to the presence of an occipital seizure focus. A history of flickering photopsias that begin and terminate abruptly and remain stationary rather than enlarging in a crescendolike fashion suggests the possibility of an occipital AVM or other seizure focus, as opposed to migrainous cortical phenomena; it also indicates the need for neuroimaging and EEG.390 Darkening or dimming of the homonymous visual field is also suggestive of seizure activity.390 In patients with an AVM, the visual disturbances start and almost always remain on the same side of the visual field (contralateral to the lesion), and headaches

Table 5.2  Causes of unexplained visual loss in children

Refractive abnormalities

 Bilateral high hyperopia

 Bilateral meridional amblyopia Cornea

 Early keratoconus

 Mucolipidosis IV

Retina

 Stargardt disease

 Cone dystrophies (congenital cone dystrophy, early progressive cone   dystrophy, blue-cone monochromatism)

 AIBSE, MEWDS, and related disorders

 Oligocone trichromacy

 Isolated foveal hypoplasia

 Bradyopsia

 Old ROP

Optic nerve

 Early bilateral optic neuritis

 Mild or segmental optic nerve hypoplasia

 Mild optic atrophy

Central Nervous System

 Structural

   Suprasellar tumors (craniopharyngioma, chiasmal glioma)

   Cortical visual loss

   PVL

   Alexia without agraphia

   Congenital prosopagnosia

 Nonstructural

   Amblyopia (due to transient amblyogenic factors)

   Monofixation syndrome

   Posttraumatic blindness

are usually localized to the side of the lesion and often lack the typical pulsatile quality of migraine.390

There is some evidence to suggest that occipital mass lesions may also predispose patients to developing classic migraine headaches.279 Troost et al390 reported a patient with an occipital AVM who described typical fortification scintillating scotomas lasting less than 30 min, with “buildup” that preceded a pulsatile headache with nausea. After removal of the AVM, the migrainous attacks resolved. Riaz et al331 described a similar patient