reaction involving complex formed and unformed visual hallucinations, often with auditory-visual synesthesia (the transformation of a sound stimulus into a visual experience).419 Individuals ingesting LSD often report that they can see music or that they can hear pictures translated into sound. In some individuals, sounds of different frequencies evoke different visual hallucinations.228,405

A second perceptual abnormality is a delayed phenomenon involving visual flashbacks. Visual flashbacks have been estimated to occur in 5% of hallucinogenic drug users.229 Symptoms include alterations of color perception, positive and negative afterimages, illusions of movement, halos around objects, shimmering of images, micropsia, macropsia, teleopsia, and palinopsia.322 These phenomena are not dose-related. They may occur after only one exposure to LSD or may begin long after cessation of the drug. Flashbacks are usually episodic but, in some cases, persist indefinitely.1,13,186,229

Cannabinoid Use

Abnormal visual perceptions may be described by patients who use marijuana or hashish or who have recently discontinued their use. Symptoms include the following: (1) black and white spots flickering at high frequency, similar to interference on a television screen, (2) a perceived reduction in depth perception, (3) visual perseveration after looking at bright objects, and (4) the perception of moving objects as a series of still pictures.210,229 These symptoms are made worse by physical exertion or staring at bright objects. Because chronic marijuana and hashish consumption is widespread in our society and common in teenagers, a history of illicit drug use should be suspected in teenagers with these symptoms.

Toxic and Nontoxic Drug Effects

Antimetabolites and Cancer Therapy

Seizure activity, complex visual hallucinations, and cortical blindness have all been described in patients with cyclosporin neurotoxicity.166,362,397 Transient or permanent visual loss has been reported among other neurological complications in patients receiving a variety of anticancer agents, including L-asparaginase and vinca alkaloids, methotrexate, FK506, methylprednisolone, and tiazofurin.47,319–321,328,334,362 The mechanisms for these neurological complications are multiple. The vinca alkaloids may cause direct damage to neuronal cells by interfering with microtubule function.440 Alternatively, arterial spasm in arteritis has been postulated as a cause in some patients.334 Some authors have noted a pattern of lesions demonstrated by CT and MR imaging that is more characteristic

of intravascular venous thrombosis rather than direct neural toxicity or arterial disease. It is well known that coagulation abnormalities are a complication of cancer, including the commonly encountered myeloproliferative disorders of childhood.275,315 It has also been postulated that there may be direct myelin toxicity in patients whose neuroimaging shows mainly white matter abnormalities.362 A confusing syndrome of delayed visual loss with neurological decline may be seen in leukemic patients following bone marrow transplantation with fludaribine immunosuppression.

Fludaribine neurotoxicity, which is seen 18–60 days after exposure, can produce a progressive syndrome of visual loss, encephalopathy, paraparesis, coma, and death. This devastating complication is reported in 18% of treated patients. MR imaging shows hyperintensity in the periventricular and periatrial white matter that does not enhance and shows restricted diffusion.59,408 The mass effect and the periventricular location on MR imaging and restricted diffusion help distinguish this condition from progressive multifocal leukoencephalopathy which is subcortical in location.223

Digitalis

Digitalis has been known for many years to cause xanthopsia (yellow vision) in toxic dosages. Other visual abnormalities associated with digitalis toxicity include scintillating scotomas, defects in the yellow/blue color vision, and paracentral scotomas. Electroretinograms (ERGs) obtained in patients with digitalis toxicity have shown decreased cone-mediated wave forms and increased photopic b-wave implicit times. Symptoms of digitalis toxicity may be the result of abnormalities of sodium and potassium metabolism of the cellular membrane, leading to abnormal photoreceptor polarization.416

Erythropoietin

Recombinant human erythropoietin is widely used in patients on dialysis to treat the anemia of chronic renal failure. Steinberg369 described moving formed visual hallucinations without delirium or psychosis, in patients who were being treated with erythropoietin.

Atropine (Anticholinergic Drugs)

Atropine can serve as a model drug for the toxicity of all anticholinergics. Visual system toxicity may be produced by overadministration of these drugs therapeutically or by encountering these in the form of belladonna, jimson weed, and stramonium. The neuropsychiatric features specifically include agitated behavior with formed visual hallucinations that frequently involve seeing insects and small animals on clothing or blankets, as well as disorientation to person, time,

and place. Treatment is usually supportive, but cholinergic agonist therapy that penetrates the bloodbrain barrier, such as physostigmine, may hasten recovery.142

Carbon Monoxide

Carbon monoxide poisoning causes hypoxia of neural tissue due to the reduced oxygencarrying capacity of blood that has had a portion of its hemoglobin converted to carboxyhemoglobin. The principle complication is CNS dysfunction. Transient visual loss of cortical origin is frequently encountered, and vision may wax and wane for several days during recovery. Visual hallucinations and agnosia have also been reported. Optic nerve damage has also been reported, but the retina is unaffected.142

Summary of Clinical Approach to the Child with Transient Visual Disturbances

Our approach to the child with transient visual disturbances is summarized in Fig. 5.6. It includes:

1. Obtaining a detailed attack history, personal profile, and family history to determine the likelihood of migrainous phenomena and to rule out other readily identifiable causes, such as drug ingestion, entoptic phenomena, transient visual obscurations, or Uhthoff phenomenon. Inquire about congenital heart disease, rheumatic fever, and cardiac symptoms (e.g., palpitations or shortness of breath unrelated to vigorous activity). Ask whether the child has had previous epileptic events and specifically inquire about contraversive eye movements, blinking, automa-