whose typical migraine headaches resolved following resection of a meningioma. The authors speculated that activation of intradural and extradural arteriovenous shunts, by a vascular meningioma, could effectively create a migraine diathesis.

Vigabitrin-Associated Visual Field Loss

Vigabitrin is an excellent antiepileptic drug that has found application in children with otherwise intractable epilepsy. Vigabitrin is an irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase, which is used in the treatment of epilepsy. One of the side effects associated with vigabitrin is persistent visual field constriction, which electrophysiologic studies suggest may be due to the toxic effects of vigabitrin on the retina. The visual field constrictions are often localized binasally, and mfERG has been used to evaluate topographical retinal dysfunction.32,159,221,251,316,341 mfERG demonstrates reduced generalized or peripheral mfERG response amplitudes. In some cases, these abnormalities correlate with the visual field defects, while in others, they are more diffuse than the visual field abnormalities. One limitation of this technique has been the restriction of mfERG responses to the central 50–60 degrees of retina, so that more peripheral retinal dysfunction may go undetected.

Posttraumatic Transient Cerebral Blindness

Occipital head trauma in children may produce a syndrome of transient cerebral blindness. This condition occurs preferentially following occipital head trauma, and there may be a delay of minutes to hours between the trauma and the onset of the blindness. The blindness is often accompanied by other symptoms, including somnolence, confusion, agitation, and vomiting. The duration of blindness may range from several hours to a day, and the prognosis for return to normal vision is excellent.

Electroconvulsive discharges are sometimes recorded from the occipital head regions during the first day following the injury. Greenblatt143 has called attention to the strong migraine and seizure diathesis in children who develop this syndrome, and suggested that vasomotor and neuronal instability may be important factors in its pathogenesis. The “ding” injury in football may produce a transient confusional state indistinguishable from transient global amnesia. These patients may have migraine features, and it has been suggested that most cases of transient global amnesia are migrainous.

The possibility of arterial dissection should be considered in children who present with transient visual loss following head or neck trauma.165,326 Carotid artery dissection presents with a nonthrobbing headache ipsilateral to the dissection.

The pain may be retro-orbital and extend to the face and neck. It is often accompanied by a bad taste in the mouth. The telltale neuro-ophthalmologic sign in carotid dissection is an ipsilateral postganglionic Horner’s syndrome. Carotid artery dissection may produce transient monocular visual loss or scintillating scotomata with headache, which simulates a migraine headache.327 Vertebral artery dissection is characterized by posterior headache or neck pain, which may be accompanied by other brainstem signs of vertebrobasilar ischemia. The most common visual symptoms include transient visual symptoms and diplopia. Treatment of arterial dissection usually consists of followed by administration of an antiplatelet agent.165 Surgical intervention is an option in patients with progressive neurological deficits.

Cardiogenic Embolism

Heart disease is considered to be the most common cause of stroke in children.332 Cerebrovascular emboli from the heart have been associated with a number of congenital and acquired disorders. Potential sources of cardiac emboli include left atrial myxoma, vegetative valvular lesions associated with bacterial endocarditis or old rheumatic heart disease, mitral valve prolapse, and atrial septal defects (including patent foramen ovale), which may be associated with right- to-left shunting of “paradoxical emboli.”431 Heart defects with a right-to-left intracardiac shunt can also cause polycythemia, with potential for thrombosis.332 Most of these conditions can be identified by echocardiography. However, the demonstration of a cardiac abnormality in a child with a previous stroke or with transient neurological disturbances does not constitute proof that the cardiac lesion is causative.

Emboli from the venous circulation are ordinarily unable to enter the systemic arterial circulation because they are filtered by the lungs. A patent foramen ovale provides venous emboli direct access to the systemic circulation and may be a source of “paradoxical” embolism that can cause cerebral and retinal dysfunction in patients of all ages.431 As with mitral valve prolapse, the subject of patent foramen ovale has generated considerable interest as more sensitive echocardiographic techniques have revealed a higher prevalence of anatomical defects than was previously recognized. Specifically, a number of recent studies have attempted to define the risk of developing neurological dysfunction when a patent foramen ovale is present. Several studies have found a significantly higher prevalence of patent foramen ovale in patients with stroke (40% vs. 10%) and transient cerebral ischemic events than in control patients.224,431 One recent study224 found that the association of mitral valve prolapse with stroke is not significant when controlled for the presence of a patent foramen ovale.224

Transesophageal echocardiography has proven to be more sensitive than routine transthoracic echocardiography for detecting patency of the foramen ovale in older patients.84,431 In infants and young children, transesophageal echocardiography requires general anesthesia. Many pediatric cardiologists reserve transesophageal echocardiography for cases in which there is a high index of suspicion for intrinsic cardiac disease. More recently, contrast transcranial Doppler imaging with Valsalva maneuver has been used to noninvasively diagnose patent foramen ovale in children.29a

The diagnosis of paradoxical embolism associated with a patent foramen ovale should be considered in children with cerebral or retinal ischemic events who (1) have been at prolonged bedrest, (2) have a history of lower extremity or pelvic fracture (producing the potential for venous stasis), and (3) have symptoms brought on by a Valsalva maneuver (which can reverse the normal intracardiac left-to-right pressure gradient).38 Associated venous thrombosis may be clinically occult, with no detectable signs of thrombophlebitis.224 Treatments for patent foramen ovale with paradoxical emboli include anticoagulation, interruption of the vena cava, or surgical closure of the foramen ovale.224 Many cardiologists are unenthusiastic about closing a patent foramen ovale surgically, even in children who have had cerebral ischemic events.

Nonmigrainous Cerebrovascular Disease

An exhaustive list of systemic vasculopathies and coagulopathies has been associated with stroke in children.332 Many of these conditions also produce retinal vascular occlusions. These include systemic vascular disease (e.g., hypertension), hemoglobinopathies (e.g., sickle cell disease), coagulopathies (e.g., antiphospholipid antibody syndrome, protein C deficiency, protein S deficiency), collagen vascular diseases (e.g., systemic lupus erythematosus), and structural vasculopathies (e.g., Moyamoya disease).332 Nantowicz and Kelley285 have summarized the many hereditary disorders that predispose to embolic, thrombotic, or hemorrhagic stroke. Certain rare conditions, especially Moyamoya disease, can present with transient visual loss or scintillating scotoma.277 Whether all of these conditions can produce transient visual loss in children is unclear, because children with known cerebrovascular disease are rarely asked about previous visual symptoms. Statistically, children with transient visual loss rarely turn out to have cerebrovascular disease as the underlying cause. Furthermore, a positive laboratory study does not necessarily establish a cause for the visual symptoms. Investigative studies are generally reserved for children who display other systemic signs of vascular disease, or who have had a previous stroke or retinal vascular occlusion.

The MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) can frequently present

with transient visual loss in early childhood.103 These children have episodes of vomiting, migrainelike headaches, seizures, and stroke-like events. Initially, there may be surprising improvement with partial recovery, but recurrent stroke-like episodes leave these children with mental deterioration, hemiparesis, hemianopsia, or blindness. Additional neuro-oph- thalmologic findings include chronic progressive external ophthalmoplegia, optic atrophy, and atypical pigmentary retinopathy with macular involvement.339 Other systemic abnormalities may include short stature, sensorineural deafness, and muscle weakness.139 Ragged-red fibers and complex I deficiency is usually seen in their muscle biopsies, and serum lactate levels are elevated.139 Similar features may be found in family members. MR imaging shows multifocal areas of hyperintense signal confined to the cortex of the cerebrum, cerebellum, and immediately adjacent white matter, with relative sparing of deep white matter.264 Several mitochondrial DNA mutations have been associated with MELAS syndrome.170

Miscellaneous Transient Visual Disturbances

in Children

Transient Visual Obscurations Associated with Papilledema

Transient visual obscurations associated with increased intracranial pressure may be monocular or binocular. They may be described by the child as a graying out or a blurring out of the vision and usually last only a few seconds at a time. There is usually a buildup in the frequency of the obscurations over time until a diagnosis is made. The child may describe dozens of these episodes over the course of a day. Precipitating factors may include rapid changes in position or Valsalva maneuvers; however, the obscurations may occur with no precipitating event. These transient visual obscurations can be distinguished from migraine by their frequency, lack of any positive visual scotoma, and the rapidity with which they come and go. In our experience, most children with elevated intracranial pressure present initially with complaints of headache, nausea, and vomiting and acknowledge transient visual disturbances only when asked. Transient visual disturbances are rare as a presenting symptom.

Headaches associated with elevated intracranial pressure share a number of similarities with migraine headaches. Like migraine headaches, these headaches are made worse by coughing, sneezing, or changes in posture, and they are not relieved by mild analgesics, such as acetaminophen. Headaches associated with increased intracranial pressure tend to be worse in the reclined position, causing some patients to prop themselves up to sleep in a position that reduces venous pressure. Unlike migraine headaches, they are rarely of sufficient severity to necessitate an emergency

department visit (excruciating headaches are rarely caused by brain tumors). They are frequently present on awakening, in contradistinction to migraine headaches, which are usually relieved by sleep. In a comparison study of headache characteristics in patients with migraine versus brain tumors, Rossi and Vassella337 found nocturnal headache, headache present on arising, and increased frequency of headache, to be most predictive of brain tumor. The authors noted that progressive neurological symptoms or signs appeared within 4 months of the headache onset in 94% of cases with tumors. However, elevated intracranial pressure headaches cannot always be clinically distinguished from migraine, because vascular symptomatology may also accompany the headache of elevated intracranial pressure. Children with preexisting migraine headaches can also develop brain tumors.

Anomalous Optic Discs

Transient visual loss has been documented in eyes with anomalous elevated optic discs, including pseudopapilledema with and without visible drusen, and congenitally tilted discs. Most reported cases are in adults, suggesting that the disc elevation may have to reach some critical degree before visual symptoms develop. Lorentzen245 reported an 8.6% incidence of visual obscurations (and, in some cases, amaurosis) in patients with disc drusen. Sadun et al343 proposed a vascular hypothesis by which both papilledema and anomalous elevation of the optic discs lead to increased interstitial pressure and decreased perfusion pressure in the intraocular portion of the optic nerve. Thus, minor fluctuations in arterial, venous, or cerebrospinal fluid pressure would result in brief but critical decrements in perfusion, leading to transient

obscurations of vision. Katz and Hoyt191 recently described an uncommon disorder associated with anomalous optic discs and posterior vitreous detachment.191 They described a group of young myopic Asians (ages, 11–42 years) whose optic discs were mildly dysplastic and slightly elevated. These patients manifested intrapapillary and subretinal peripapillary hemorrhages with incomplete posterior vitreous detachment. Visual symptoms were mild (blur, spot, smudge) or absent, but abnormalities were detected on visual field testing in most cases. They suggested that elevated anomalous optic discs may have abnormal vitreopapillary adhesions and may be unusually susceptible to vitreous traction.

Transient visual loss can also occur in patients with excavated optic disc anomalies.141,359 Graether141 described a young adult who had episodes of amaurosis accompanied by transient dilation of the retinal veins in an eye with a morning glory disc anomaly. Brodsky42 reported an almost identical case in a 10-year-old boy (Fig. 5.5). Seybold359 described a young adult who had transient visual obscurations in an eye with a peripapillary staphyloma. In both cases, the amaurosis could be induced by light stimulation.

Entoptic Images

Entoptic images are formed by the reproducible perception of objects in the eye, the anatomical structures of the eye, or the perception of the consequences of nonphotic stimulation of the visual sensory apparatus of the eye. Under normal circumstances, these stimuli are either not perceived or ignored; however, under special viewing circumstances, they may become manifest. Although children are less likely than adults to report them, there is no reason to believe that they are less able to perceive them.

Media Opacities

The common entopic phenomenon of the perception of vitreous floaters seen in adults occurs by a similar mechanism in children. Posterior vitreous detachment is only rarely seen in children, but children with vitreous hemorrhages may report the characteristic movement of shadows as the blood clears. Perceptive and articulate children with corneal or lenticular opacities are sometimes able to see the opacity and describe the circumstances in which they become most apparent to them, such as with variability in illumination.

Retinal Circulation

Lepore226 found Uhthoff symptom in 18 of 100 patients with pregeniculate visual loss; ten had multiple sclerosis, four had compressive lesions, and four had other lesions. Neither the extent of visual field loss, decreased acuity, or binocular deficits correlated significantly with Uhthoff symptom. Thus, Uhthoff symptom is strongly but not invariably associated with multiple sclerosis. It has been suggested that hyperthermia is not the exclusive cause of Uhthoff symptom and that changes in metabolic status and ionic channel kinetics that alter the conduction properties of demyelinated fibers can cause this phenomenon.226,358,410

Alice in Wonderland Syndrome

Children may independently report the flying capillary phenomenon that consists of bright dots of light moving away from the blind spot area when looking at a Ganzfeld-like background (e.g., the sky), or a large, uniform surface (e.g., ceiling or light-colored painted wall).

Phosphenes

The production of phosphenes by pressing on the eye is a particularly important phenomenon when dealing with children with low vision, especially of retinal origin. The repetitive finger poking in the eye in order to produce these sensations by the otherwise blind child may result in atrophy of orbital fat and discoloration of the lids and periorbital tissues. Strategies to keep the child otherwise occupied may prevent these disfiguring consequences. However, the determined child will be very difficult to dissuade from this activity. Phosphenes on eye movement and with sudden loud noises have been reported in young adults with optic neuritis, and this has been likened to the Lhermitte sign.76,228

Uhthoff Symptom

In patients with multiple sclerosis, minor elevation of body temperature by external causes or physical activity increases neural transmission but rapidly leads to electrophysiological blockage through areas of demyelination. This phenomenon, termed Uhthoff symptom, commonly affects the optic nerve, causing visual blurring or amaurosis lasting minutes to an hour. It is less common in children than adults, presumably due to the lower incidence of multiple sclerosis in children. Transient monocular diminution in vision can be brought on by bathing in hot water, hot weather, exercise, consuming hot food or drink, and less frequently, by emotional disturbances, fatigue, menstruation, increased lighting, smoking, or cooking.226

In 1952, Lippman238 used the term Alice in Wonderland syndrome to describe the impairment of time sense and body image in a patient with migraine. Todd387 later used the term to describe the strange distortions of body size and distance from their surroundings perceived by patients with migraine, epilepsy, hypnotic states, drug intoxication with lysergic acid diethylamide (LSD) or marijuana, fever, cerebral lesions, and schizophrenia. Copperman64 reported the association between infectious mononucleosis and Alice in Wonderland syndrome in three children whose symptoms included macropsia, micropsia, metamorphopsia, teleopsia, xanthopsia, and a detached feeling. Numerous children have since been noted to develop these acute perceptual disturbances, usually during the acute phase of infectious mononucleosis64,144,235,346 and as an accompaniment of juvenile migraine.136 The condition is self-limited and requires no specific treatment.

Charles Bonnet Syndrome

Healthy elderly patients with bilaterally decreased vision may experience vivid, formed hallucinations in the absence of a psychiatric disorder (termed the Charles Bonnet syndrome).135 The type of hallucinations in Charles Bonnet syndrome may reflect segregation of hierarchical visual pathways into streams.348 These vivid images are believed to represent release hallucinations because they occur in the absence of CNS pathology and may cease following improvement in vision.293 These hallucinations have the following general features: (1) They are exclusively visual, complex, well formed, and often lifelike in their actions, frequently involving people and places. (2) They occur with insight and an otherwise clear consciousness; affected patients know they are hallucinating. (3) The hallucinations are devoid of emotional content (unlike those of peduncular hallucinosis, which is associated with a pleasurable affective reaction). (4) They are superimposed on, or occur in combination with normal perceptions. (5) They are brief, lasting a few minutes at most.