Physicians routinely measure visual acuity by having the patient read from either a Snellen wall chart or a hand-held card (Fig. 12-2). A person with “normal” visual acuity can read 3/8-inch (0.6-cm) letters at a distance of 20 feet (6.1 meters). This acuity, the conventional reference point, is designated 20/20. People with 20/40 acuity must be as close as 20 feet (6.1 meters) to see what a person with normal acuity can see at a distance of 40 feet (12.2 meters).

FIGURE 12-2 Physicians should hold this hand-held visual acuity chart 14 inches (36 cm) from patients and test each individual eye. The smallest line that they read without a mistake determines their visual acuity. For neurologic evaluations, patients should wear their glasses or contact lenses.

Optical Disturbances

People with myopia have decreasing visual acuity at increasingly greater distances. Myopia first becomes troublesome during adolescence when it causes difficulty with seeing blackboards, watching movies, and driving. Because reading and other close-up activities, which require “near vision,” remain unimpaired, the lay public commonly labels people with myopia “nearsighted.”

The usual causes of myopia are optical rather than neurologic, such as a lens that is too “thick” or a globe that is too “long” (Fig. 12-3). Occasionally medicines cause myopia. For example, topiramate (Topamax), a widely prescribed antimigraine and antiepileptic drug (AED), may produce an acutely occurring but transient myopia. (Topiramate can also lead to angle closure glaucoma [see later].)

FIGURE 12-3 Image focusing in hyperopic (farsighted) and myopic (nearsighted) eyes. A, In normal eyes, the lens focuses the image on to the retina. B, In hyperopic eyes, the shorter globe or improperly focusing lens causes the image to fall behind the retina. C, In myopic eyes, the longer globe or improperly focusing lens causes the image to fall in front of the retina. Lenses can compensate for the refractive errors of hyperopia and myopia. Alternatively, laser or surgical “flattening” of the lens may correct myopia.

In myopia’s counterpart, people with hyperopia or hypermetropia have decreasing visual acuity at increasingly shorter distances. The lay public commonly labels them “farsighted” because they can only see distant objects, such as street signs, rather than closely held ones, such as newspapers and computer screens. In hyperopia or farsightedness, the lens is usually too “thin,” rendering its refractive strength insufficient. Occasionally the globe is too “short.”

In presbyopia, older individuals cannot focus on closely held objects because their relatively inelastic and dehydrated lenses are unable to change shape. With their impaired near vision, people with presbyopia, as well as those with hyperopia, tend to hold newspapers and sew with needles at arms’ length. Reading glasses usually can compensate for the refractory defect by bringing the focal point into the proper working distance. (Older individuals and those with diabetes also tend to have small pupils [miosis] that should not be mistaken for Argyll Robertson pupils [see later].)

Disruption of the accommodation reflex is another common cause of visual disturbance. Normally, when a person looks at a closely held object, efferent fibers from this reflex contract the ciliary body muscles to thicken the lens so that the image falls on the retina. These fibers also cause miosis and increase convergence muscle tone. For example, when a person begins to read the screen of an iPad, the eyes converge, the pupils constrict, and each lens thickens to provide greater refraction. In other words, the reflex accommodation focuses the image of closely held objects on the retina.

Because the parasympathetic nervous system mediates the accommodation reflex, many medications with anticholinergic side effects impair visual acuity for closely held objects (Fig. 12-4). These medicines – selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and clozapine – produce blurred vision mostly because their substantial anticholinergic properties impair patients’ accommodation reflex. For example, duloxetine (Cymbalta) causes blurred vision in approximately 3% of patients; sertraline (Zoloft) and paroxetine (Paxil), 4%; and venlafaxine (Effexor) at 75 mg, 9%. This side effect may be unsuspected because these medicines can impair accommodation without producing other anticholinergic effects, such as dry mouth, constipation, and urinary hesitancy.

FIGURE 12-4 Accommodation and accommodation paresis. A, When looking at a distant object, parallel light rays are refracted little by a relatively flat lens on to the retina. B, Accommodation: when looking at a closely held object, ciliary muscle contraction increases the curvature of the lens, greatly refracting the light rays. C, Accommodation paresis: If the ciliary muscles are paretic, the lens cannot form a rounded shape. Its weakened refractive power focuses light rays from closely held objects behind the retina; however, parallel light rays from distant objects still focus on the retina. Therefore, accommodation paralysis blurs closely held objects but leaves distant ones distinct.

Abnormalities of the Lens, Retina, and Optic Nerve

Cataracts (loss of lens transparency) result from complications of old age (senile cataract), trauma, diabetes, myotonic dystrophy (see Chapter 6), and chronic use of certain medicines, such as steroids. In prolonged, high doses, phenothiazines and some second-generation neuroleptics may produce minute lens opacities, but ones rarely dense enough to impair vision.

Pigmentary changes in the retina can be a manifestation of injuries, degenerative diseases, diabetes, infection, or the use of massive doses of phenothiazines (Fig. 12-5). Among infants and children, nonaccidental head injury (child abuse), particularly violent head shaking or direct trauma, creates retinal hemorrhages. Other stigmata of repeated trauma – spiral fractures of the long bones, multiple skull fractures, and burns (see Chapter 22) – frequently accompany these retinal hemorrhages.

FIGURE 12-5 Massive doses of thioridazine (Mellaril) may induce retinal hyperpigmentation – described as “black bone spicules” or “salt and pepper.” Before these retinal pigmentary changes are visible on fundoscopic examination, patients may complain of blurred vision or impaired nighttime vision.

In 25% or more of Americans older than 65 years, the cells of the retina’s pigment epithelium, mostly in the macula, degenerate through a variety of mechanisms, including proliferation of the underlying blood vessels. When degeneration involves cells in the macula, a condition known as macular degeneration, it distorts patients’ critical central vision. Patients characteristically lose their reading ability. With their remaining peripheral vision, patients negotiate around their living areas. However, progressive deterioration deprives patients of all their eyesight. As with individuals who develop blindness from any cause, those beset by macular degeneration are at risk of losing their self-sufficiency, appearing to have cognitive dysfunction, and experiencing visual hallucinations (especially if they also have hearing or cognitive impairments [Box 12-1]).

Among acquired immunodeficiency syndrome (AIDS) patients, opportunistic organisms, such as cytomegalovirus, infect the retina. Current anti-AIDS regimens have greatly reduced visual complications. In a more benign situation, several medicines lend a visual discoloration. For example, digoxin, at toxic concentration, casts a transient yellow hue (xanthopsia [Greek, xanthos yellow + opsis sight]), and sildenafil (Viagra), a blue or yellow hue. On the other hand, a few, such as the AED vigabatrin (Sabril), sometimes cause permanent retinopathy.

Optic Nerve

Injuries of the optic nerves, which are projections of the central nervous system (CNS), result in visual loss that may be limited to a scotoma (an area of blindness [see Fig. 15-2]), but may encompass the entire visual field. In addition, because the optic nerves serve as the afferent limb of the light reflex, optic nerve injury also causes an afferent pupillary defect: When the examiner shines light into an eye with optic neuritis, both pupils fail to constrict; however, when the same light shines into the unaffected eye, both pupils normally constrict (see Fig. 4-2). With time, optic nerve injuries usually cause atrophy, revealed by the fundoscopic examination showing pallor of the optic head.

Optic nerve injuries may occur either as isolated conditions or ones accompanied by injuries of the cerebrum or other part of the CNS. One of the most common, inflammation of one or both optic nerves, optic or retrobulbar neuritis, causes sudden, painful visual loss (Fig. 12-6), as well as an afferent pupillary defect. In addition, they see “desaturated” colors with their remaining vision. For example, patients cannot appreciate the difference between fire engine red and brick red. In severe cases, they cannot distinguish red from green.

FIGURE 12-6 Neurologists consider the optic disk, which they can see on fundoscopic examination, to be the bulbar portion of the optic nerve. They consider the long segment of the optic nerve behind the eye its retrobulbar portion. Depending on where an inflammatory condition, such as multiple sclerosis, attacks the optic nerve, patients develop optic or retrobulbar neuritis. Visual loss, pain on eye movement, and color desaturation characterize optic and retrobulbar neuritis.

When optic neuritis affects the optic disk, which is the most anterior segment of the optic nerve, physicians will often see inflammation of the disk (papillitis) on fundoscopic examination. If the inflammation affects only the segment of the optic nerve posterior to the disk, as in retrobulbar neuritis, physicians will be unable to see any abnormality of the optic disk on fundoscopic examination.

Of the many conditions that cause optic neuritis, demyelinating illnesses, particularly multiple sclerosis (MS) and its close relative neuromyelitis optica (NMO), are the most common (see Chapter 15). Most importantly, optic neuritis frequently precedes the appearance of other manifestations of MS and complicates the course of most cases. If an otherwise asymptomatic patient develops optic neuritis and the magnetic resonance imaging (MRI) shows two or more hyperintense lesions in the brain, that patient has greater than a 70% risk of developing MS. On the other hand, an otherwise asymptomatic optic neuritis patient who has no MRI lesions has only a 25% risk of developing MS.

With recurrent optic or retrobulbar neuritis attacks, the optic nerve becomes atrophic, the disk white, the pupil unreactive, and the eye blind. A course of high-dose, intravenous steroids may shorten an attack, but probably does not alter the outcome. Physicians cautiously use steroids because they can produce mental aberrations, including euphoria, agitation, and, in the extreme, psychosis.

Toxins, including some medications, can also damage the optic nerves. In one scenario, alcoholics inadvertently drink methanol (CH₃OH), a solvent component of antifreeze and cooking fuels, such as Sterno, and an illicit adulterant of everyday ethanol (C₂H₅OH) drinks. Drinking methanol causes a combination of gastroenteritis, delirium, and visual problems, particularly blurry vision and scotoma. With severe methanol intoxication or merely its chronic intermittent consumption, optic nerves atrophy and victims become blind.

An inflammatory condition of the arteries that supply the optic nerve, temporal or giant cell arteritis, often leads to ischemia of the optic nerves. Moreover, the arteritis tends to spread to the cerebral arteries (see Chapter 9). Typically affecting only people older than 65 years, temporal arteritis often first causes a mild to moderate, prolonged (weeks to months) illness featuring headache accompanied by systemic symptoms, such as malaise, prolonged aches, and pains. The number and variety of these initial nonspecific symptoms understandably lend the appearance of depression or a somatoform disorder. However, physicians should avoid missing this diagnosis because, unless they promptly treat the patient with high-dose steroids, it can result in blindness and strokes. Finding giant cells and other signs of inflammation on a temporal artery biopsy will confirm the diagnosis.

Leber hereditary optic atrophy, an illness attributable to a mitochondrial DNA mutation, also involves the optic nerves, but no other part of the CNS or the musculature (see Chapter 6). Most commonly affecting young males, it causes visual loss culminating in blindness in one and then, within months, the other eye.

Several conditions simultaneously affect the cerebrum and the optic nerves. These conditions produce cognitive decline and personality changes as well as blindness. MS would be one example. Another is the storage lysosomal storage disease due to a deficiency in hexosaminidase-A, Tay–Sachs disease, which is almost always fatal by age 5 years.

Another classic example of simultaneous injury of both the optic nerve and cerebrum is an olfactory groove or sphenoid wing meningioma. This tumor compresses the near-by optic nerve (see Chapters 19 and 20) and burrows into the overlying frontal or temporal lobe. The cerebral damage can trigger complex partial seizures and cause cognitive decline and personality changes. At the same time, optic nerve damage causes optic atrophy and blindness in one eye.

Similarly, tumors of the pituitary region, such as adenomas or craniopharyngiomas, may also produce visual loss accompanied by psychologic changes. Unless detected and removed early, these tumors grow slowly upward to compress the optic chiasm and hypothalamus and downward to infiltrate the pituitary gland (see Fig. 19-4). Compression of the optic chiasm causes the pathognomonic bitemporal hemianopsia. Compression of the hypothalamus and pituitary causes headache and panhypopituitarism: decreased libido, diabetes insipidus, loss of secondary sexual characteristics, and sleep disturbances.

Glaucoma

In most cases, glaucoma consists of elevated intraocular pressure resulting from obstructed outflow of aqueous humor through the filtration angle of the anterior chamber of the eye (Fig. 12-7) – not from increased production of aqueous humor. Psychiatrists should recognize two common varieties – open-angle and angle closure – although only certain psychotropic medications occasionally produce the angle closure variety. If glaucoma remains untreated, it damages the optic nerve, causes visual field impairments, and eventually leads to blindness.

FIGURE 12-7 A, Open-angle glaucoma: The aqueous humor does not drain despite access to the absorptive surface of the angle. Impaired flow from the eye leads to gradually increased intraocular pressure (glaucoma). B, Narrow-angle glaucoma: When the iris moves forward, as may occur during pupil dilation, the angle is narrowed or even closed. Obstruction of aqueous humor flow leads to angle closure glaucoma.

Open-Angle Glaucoma

Open-angle or wide-angle glaucoma occurs seven times more frequently than closed-angle glaucoma. People at greatest risk are those who are older than 65 years, diabetic, myopic, and relatives of glaucoma patients. Because symptoms are usually absent at the onset, this variety of glaucoma might be diagnosed only when an ophthalmologist detects elevated intraocular pressure, certain visual field losses, or changes in the optic nerve. Later, when central vision or acuity is impaired, the optic cup is abnormally deep and permanently damaged. Lack of symptoms in the initial phase of open-angle glaucoma is one of the most compelling reasons for annual ophthalmologic examinations.

Open-angle glaucoma usually responds to topical medications (eyedrops) or laser treatment. Psychotropic medications do not precipitate open-angle glaucoma. In general, patients with open-angle glaucoma may be given antidepressants and other psychotropic medications provided that their glaucoma treatment is continued.

Angle Closure Glaucoma

In angle closure glaucoma, which is also called closed-angle or narrow-angle glaucoma, intraocular pressure is usually elevated by impaired aqueous humor outflow at the filtration angle (see Fig. 12-7). In one variety, the fluid becomes trapped behind the iris. Patients with narrow-angle glaucoma usually are older than 40 years and often have a family history of the disorder, but they also frequently have a history of hyperopia and long-standing narrow angles. Few have had symptoms, such as seeing halos around lights, preceding an attack of angle closure glaucoma. In contrast to the relatively normal appearance of the eye in open-angle glaucoma, in acute angle closure glaucoma the eye is red, the pupil dilated and unreactive, and the cornea hazy. Moreover, the eye and forehead are painful, and vision is impaired.

Angle closure glaucoma is sometimes iatrogenic. For example, when pupils are dilated for ocular examinations, the “bunched-up” iris can block the angle (see Fig. 12-7, B). Likewise, medicines with anticholinergic properties, probably because they dilate the pupil, can precipitate angle closure glaucoma.

Despite the attention to the potential problem, the complication rate of glaucoma with tricyclic antidepressant use is low, and with SSRIs it is almost nonexistent. However, as neurologists and other physicians prescribe tricyclics for increasingly numerous conditions – chronic pain, urinary incontinence, headache, and diabetic neuropathy – many patients remain vulnerable. In addition, other medications for neurologic diseases, particularly topiramate, can cause angle closure glaucoma.

Whatever the cause of angle closure glaucoma, prompt treatment can preserve vision. Topical and systemic medications open the angle (by constricting the pupil) and reduce aqueous humor production. Laser iridectomy immediately and painlessly creates a passage directly through the iris that drains aqueous humor.

Because glaucoma poses such a threat, individuals older than 40 years should have intraocular pressure measured every 2 years and those older than 65 years, every year. Most patients who are under treatment for either form of glaucoma may safely receive psychotropic medications. Glaucoma medications, such as pilocarpine (a cholinergic medicine that constricts the pupils), and ophthalmic beta-blockers, such as timolol (Timoptic), may be absorbed into the systemic circulation and create psychologic and cardiovascular side effects, including orthostatic lightheadedness, bradycardia, and even heart block. Not surprisingly, elderly patients who use beta-blocker eyedrops sometimes experience brief periods of confusion.

Children are also susceptible to systemic absorption. For example, when given scopolamine or other atropine-like eyedrops for ocular examination, children often become agitated. On the other hand, marijuana, despite claims of its proponents, is no more effective than standard medications for treating glaucoma.

Cortical Blindness

Bilateral occipital cortex injuries can produce severe visual impairment, called cortical blindness. The underlying cause may be damage limited to the occipital lobes from bilateral posterior cerebral artery occlusions or trauma. Alternatively, extensive brain injury from anoxia, multiple strokes, or MS may cause cortical blindness along with other impairments. Reflecting occipital lobe damage, electroencephalograms (EEGs) characteristically lose their normal, posterior 8–12-Hz (alpha) rhythm. Whether the cortical blindness results from limited or generalized cortex injury, the pupils are normal in size and reactivity to light because all elements of the pupillary light reflex remain intact: the midbrain and optic and oculomotor nerves (see Fig. 4-2).

Anton Syndrome

The dramatic neuropsychologic phenomenon of Anton syndrome – blind patients explicitly or implicitly denying that they have lost all vision – characteristically complicates the sudden onset of blindness. Whether the blindness stems from a blast injury of both eyes, bilateral occipital lobe strokes, or other cause, the irrational response to blindness, rather than blindness itself, constitutes Anton syndrome. These patients typically respond, as those with anosognosia (see Chapter 8), by using denial as a defense. Sometimes they simply refuse to say that they have lost vision. Others blame external factors, like dim light, for their problem. Some may, if pressed, acknowledge visual loss but confabulate by “describing” their room, clothing, and various other objects. Anton syndrome allows blind patients to behave as though they still had normal vision and proceed to stumble about their room.

For example, a 76-year-old man sustained a right-sided posterior cerebral artery stroke that was superimposed on a prior left-sided posterior cerebral stroke. He first blamed his inability to see the examiner’s blouse on poor lighting and having misplaced his glasses. He then claimed to be uninterested in the exercise. When urged, still implicitly denying his blindness, he calmly described the blouse as “lovely” and “becoming,” at one time elaborating that it was “obviously finely sewn and made from fine material.”

Depending on the patient’s premorbid state and extent of the responsible cerebral lesion, signs of generalized cerebral cortex injury, especially delirium and dementia, may accompany Anton syndrome. In addition, if the cerebral lesion extends beyond the occipital lobes, amnesia (from bilateral temporal lobe injury) or anosognosia for other deficits (from right-sided parietal lobe injury) may accompany individual cases.

Visual Perceptual Disturbances

Visual perceptual disturbances usually consist of impaired processing of visual information or inability to integrate visual information with other neuropsychologic information. Although these fascinating disturbances seem to be neatly defined, patients usually have incomplete forms. Moreover, illnesses often superimpose visual perceptual disturbances on other neuropsychologic disorders, such as dementia, aphasia, and apraxia. In these cases, patients’ impairments more than coexist: they multiply.

Palinopsia

Palinopsia (Greek, palin, again; opsis, vision), which may be likened to “visual perseveration,” consists of recurrent or persistent images following removal of the visual stimulus. Technically a form of hallucinations, the visions usually appear to the patient within an area of incomplete visual loss in the left lateral field. Patients with palinopsia often have recurrent images of objects, scenes, or family members. Frequently, several afterimages appear immediately in rapid succession as “visual echoes,” but sometimes only after hours or days. Because palinopsia consists of duplicate images of common inanimate objects, it usually does not elicit an emotional response.

Both the left lateral visual impairment and superimposed hallucinations stem from right-sided occipital and parietal lobe lesions. Palinopsia may represent a failure of the cortex to capture only a single image, but it rarely results from seizure activity. In palinopsia, compared to seizure activity, the visions are well formed, not so much hallucinations as reproductions of objects in the environment, and unaccompanied by changes in emotion or level of consciousness. Because occipital lobe discharges would be readily detectable, an EEG would readily identify seizures causing isolated repetitive visual hallucinations.

Agnosia

Another visual perceptual disturbance, visual agnosia, consists of the inability to appreciate the meaning of an object by its appearance, despite an intact visual system. Patients with visual agnosia simply cannot comprehend what they see. For example, a man would be able to describe a stop sign by saying that it is octagonal, red, and says “S-T-O-P,” but not be able to explain what action drivers must take.

Neurologists detect visual agnosia most often in patients with cognitive impairment from multiple small strokes or Alzheimer disease. They sometimes portray it as a disconnection between the visual and cognitive centers.

Visual agnosia is also a major component of the infamous, although uncommon, Klüver–Bucy syndrome. Neurosurgeons have produced this behavioral disorder in monkeys by resection of both anterior temporal lobes, which contain the amygdalae and components of the limbic system. The resulting limbic system damage produces visual agnosia so severe that the monkeys not only touch all objects, but they compulsively identify all objects by putting them into their mouth (“psychic blindness”). Their behavior can be repetitive, compulsive, and indiscriminate. When the Klüver–Bucy syndrome occurs in humans (see Chapter 16), they display a muted variation of psychic blindness, oral exploration, which consists of their placing inedible objects in their mouth, although only briefly, partly, and absent-mindedly.

Color agnosia is a particular inability to identify colors by sight. The affected individual’s problem is neither aphasia nor color blindness, which is a sex-linked inherited retinal abnormality. Patients with color agnosia cannot specify (by speech or writing) the name of colors. When shown painted cards, for example, they cannot say or write the name of the colors. Despite those deficits, patients can match pairs of cards of the same color, read Ishihara plates (pseudoisochromatic numbered cards), and recite the colors of well-known objects, such as the American flag. In striking contrast, they behave as though they appreciate colors.

In a variation of prosopagnosia, patients with right cerebral lesions cannot match pairs of pictures of unfamiliar faces. This condition represents a visual perceptual impairment possibly induced by a nondominant parietal lobe lesion.

Balint Syndrome

Balint syndrome, which neurologists attribute to bilateral parietal-occipital region damage from strokes or Alzheimer disease, consists of three related, admittedly overlapping, elements concerned with visual attention: ocular apraxia, optic ataxia, and simultanagnosia. Ocular apraxia, which neurologists sometimes call “psychic paralysis of fixation,” is the neuropsychologic inability of a patient to shift attention by looking away from an object to one located in the periphery of vision. Patients behave as though they were mesmerized by the original object or like a military radar system that has locked on to an approaching hostile aircraft. By briefly closing their eyes, which momentarily interrupts attention, patients can shift their gaze.

Optic ataxia, the second element of Balint syndrome, is the inability to look or search in a deliberate pattern. A common manifestation of this element consists of inability to read in methodical visual sweeps.

The third element, simultanagnosia, consists of being able to attend only to objects immediately in the center of vision. When confronted with objects in the center and the periphery of vision, patients will invariably ignore the one in the periphery even though it might be more important or attractive. Because of simultanagnosia, patients cannot comprehend complicated scenes or objects. For example, they would be unable to comprehend a baseball game, but instead able to see only an individual player or a base.

Psychogenic Blindness

The medical literature has stated that nonorganic visual loss, which neurologists continue to label psychogenic blindness, explains the symptom of visual loss in as many as 5% of children and adults. However, cases of psychogenic blindness that convincingly mimic true blindness are rare. Because people lack an intuitive knowledge of visual pathways, neurologists can readily detect nonanatomic patterns of psychogenic blindness. Even bedside testing can easily reveal its spurious nature.

Psychogenic blindness occurs in malingering and various psychiatric conditions, particularly in what the preliminary version of the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th edition, classifies as Conversion Disorder (Functional Neurological Symptom Disorder). One of the most common presentations of psychogenic blindness is monocular visual loss and ipsilateral hemiparesis. This combination defies the laws of neuroanatomy because the division of optic pathways at the optic chiasm provides that a cerebral lesion causing hemiparesis also causes hemianopsia – not monocular blindness. (Brainstem lesions may cause hemiparesis and diplopia, but not hemianopsia or monocular blindness.) In another presentation, individuals with psychogenic blindness often needlessly wear sunglasses. This ploy seems to serve several purposes: It signals that they are blind, reduces visual distractions, and prevents observers from seeing when their eyes establish eye contact.

Similarly, tubular or tunnel vision defies the laws of optics that dictate that the visual area should expand with increasing distance (Fig. 12-8). Important exceptions to this general rule, however, sometimes occur when patients with migraine with aura have constriction of their peripheral vision and in some patients taking vigabatrin.

FIGURE 12-8 The area seen by a person normally increases conically in proportion to the distance from the object. In tubular or tunnel vision, which defies the laws of optics, the “visible” area remains constant despite increasing distance.

To unmask psychogenic blindness, an uninhibited examiner simply might make childlike facial contortions or ask the patient to read some four-letter words. The patient’s reaction to these provocations would reveal the ability to see. When only one eye is affected by psychogenic blindness, fogged, colored, or polarized lenses in front of the unaffected eye will often confuse (or fatigue) a patient into revealing that vision is present.

Another technique that exposes intact vision is to draw a striped cloth or spin a vertically striped cylinder (drum) in front of a person. The moving striped surface will elicit optokinetic nystagmus unless true blindness is present. Likewise, having patients stare at a large, moving mirror irresistibly compels them to follow their own image.

In a different approach, neurologists offer patients eyeglasses with lenses having negligible optical strength. Wearing these glasses allows patients to extract themselves from psychogenic blindness without embarrassment.

If clinical tests are inconclusive, EEG and other electrophysiologic testing may help. Alpha rhythm overlying the occipital lobes of patients at rest with their eyes closed, and loss of that rhythm when they open their eyes, indicates an intact visual system. However, because patients’ anxiety or concentration suppresses alpha activity, its absence is not as meaningful as its presence. In visual-evoked response testing, another noninvasive electrophysiologic test, visual system injuries produce abnormal potentials (see Chapter 15).

Visual Hallucinations

Unlike auditory hallucinations, which typically result from psychiatric disorders, visual hallucinations in adults typically result from neurologic disorders. (In children, they may be a symptom of schizophrenia.) Specific qualities of visual hallucinations that should prompt a neurologic evaluation include stereotyped visions, alteration in the patient’s level of consciousness, and concurrent behavioral abnormalities. Patients usually require an imaging study, routine blood tests, urinary toxicology analysis, and an EEG.

Visual hallucinations can originate in dysfunction of the frontal, temporal, or occipital cortex. Problems as diverse as toxic-metabolic encephalopathy, dementia-producing diseases, medication side effects, and structural lesions can produce them (see Box 12-1).

Seizures

Elementary partial, complex partial, or frontal lobe seizures (see Chapter 10) can produce visual hallucinations. Seizure-induced visual hallucinations tend to be stereotyped and brief, can be “seen” in both eyes, and may even appear in a hemianopic area. They range from simple geometric forms in elementary partial seizures to detailed visions accompanied by sounds, smells, thoughts, emotions, and, characteristically, impairment of consciousness, in complex partial seizures.

Migraine Aura

The “aura” in migraine with aura (previous termed “classic migraine”) consists of sensory disturbances – olfactory, sensory, or visual. In almost all cases, auras include stereotyped visual hallucinations (see Fig. 9-2). The majority consist of distinctive crescent scotomata or scintillating, patterned zig-zag lines (fortification spectra) that move slowly across the visual field for 1–20 minutes before yielding to a hemicranial headache. In a potentially confusing situation, visual auras sometimes represent the sole manifestation of migraine. In rare individuals, migraine aura consists of elaborate visual distortions, such as metamorphopsia, in which individuals and objects appear, to the patient, to change size or shape, as in the celebrated Alice in Wonderland syndrome.

Narcolepsy

As an element of the narcoleptic triad (see Chapter 17), visual hallucinations intrude into a patient’s partial consciousness. Narcoleptic-induced visual hallucinations are essentially dreams composed of variable, unpredictable – not stereotyped – intricate visions accompanied by rich thoughts and strong emotions. They tend to occur while patients fall asleep (hypnagogic hallucinations) or awaken (hypnopompic hallucinations). As with normal dreams, these hallucinations are associated with flaccid, areflexic paresis and rapid eye movements (REMs).

Neurodegenerative Illnesses

Visual hallucinations are also a hallmark of neurodegenerative diseases that cause dementia, particularly Alzheimer, Lewy bodies, and Parkinson diseases or their treatment (see Chapters 7 and 18). When they are manifestations of these disorders, hallucinations tend to be visually complex, have a paranoid aspect, and occur predominantly at night. As a clue to dementia with Lewy bodies disease, visual hallucinations occur frequently and begin early in its course. In contrast, when visual hallucinations complicate Alzheimer disease, they occur in its late stages. Hallucinations in Parkinson disease are usually partly medication-induced.

Toxins

Many classes of medicines, in addition to anticholinergics or dopamine enhancers, may cause hallucinations. Similarly, illicit stimulants, by design, cause hallucinations. In general, medicine- or drug-induced hallucinations develop in the context of delirium. Even withdrawal from certain substances causes visual hallucinations. The best-known example is alcohol withdrawal causing delirium tremens (DTs). In this case, most patients have varied, sometimes frightening visions that stem from the environment. Agitation, confusion, fluctuating consciousness, sweating, and tachycardia accompany or overwhelm the hallucinations. In some DT patients, however, the hallucinations seem to petrify the patients who then become hypervigilant, reticent, and immobile.

Sensory Deprivation

Visual loss from either cortical blindness or bilateral eye injuries produces deprivation or “deafferentation” of the visual cortex. Without the physiologic input, unregulated visual cortex activity emerges as hallucinations. For example, soldiers sustaining extensive eye wounds have periods of “seeing” brightly colored forms and even entire scenes. Because of the potential adverse effects of blindness, cataract patients should avoid simultaneous bilateral ophthalmologic surgical procedures.

In contrast to visual hallucinations occurring in patients with dementia, delirium, or psychiatric disorder, blind individuals with no mental disorder experience visual hallucinations. When this phenomenon occurs, neurologists label it the Charles Bonnet syndrome. As if to emphasize that it originates in deafferentation, patients with hemianopsia may have hallucinations exclusively in their blind visual field.

Individuals with sudden visual loss or even slowly progressive loss from cataracts or, more frequently, macular degeneration often present with the Charles Bonnet syndrome. They usually have complex hallucinations in which they “see” long-dead relatives and friends or animals. Despite vivid elaborate imagery, affected individuals typically sit and have quiet, harmless hallucinations that do not provoke any emotional response. They are usually aware that their visions are merely hallucinations, and they may only reluctantly disclose them to their family and physicians.

With seizures, migraine, or narcolepsy, appropriate treatment of the underlying condition will usually eliminate visual hallucinations. Some techniques override the sensory deprivation. Antipsychotics and occasionally AEDs may suppress hallucinations that complicate neurodegenerative illnesses, intoxications, and acute visual loss; however, physicians should avoid administering dopamine-blocking agents to patients with dementia with Lewy bodies (see Chapter 7).

Visual Field Loss

As in so much of neurology where anatomy determines destiny, the pattern of visual loss determines localization (Fig. 12-9). However, before reading further, nonneurologists must accept that the clinical presentation of cases is potentially confusing. Neurologists create drawings of visual fields viewed from the patient’s rather than from the physician’s perspective. Neurologists show the left eye’s visual field on the left side of the drawing, and the right eye’s on the right side. In contrast, radiologists persist in generating CTs and MRIs in a horizontally reversed pattern, “right is left.” With that frame of reference, neurologists follow several guidelines, as follows.

FIGURE 12-9 The visual pathway (see Fig. 4-1), which extends from the retina to the occipital cortex, is exquisitely vulnerable throughout its entire course. Lesions produce characteristic visual field defects. The defects, in turn, indicate the lesion’s location and give hints to its etiology and expectable associated findings. A, Optic nerve lesions typically give ipsilateral scotoma. B, Optic chiasm lesions, from below, when small (smaller ring), give superior bitemporal quadrantanopsia. C, When large (larger ring), optic chiasm lesions give bitemporal hemianopsia. D, Cerebral lesions that interfere with the anterior optic tract give contralateral homonymous hemianopsia. E, Lesions that interfere with the occipital cortex give contralateral homonymous hemianopsia, sometimes with macular sparing. Although the determination of visual fields serves as a highly reliable sign of localized neurologic disease, their display is one of clinical neurology’s most confusing exercises. In the standard manner, these sketches portray visual field defects as crosshatched areas from the patient’s perspective. For example, the sketch of the left homonymous hemianopsia (D) portrays the abnormal areas on the left side of each circle – as when the patient looks at the paper. The sketch of cerebral optic tract pathways portrays the tracts as though a picture had been taken from above the patient’s brain (see Fig. 8-4). In contrast, computed tomography (CT) and magnetic resonance imaging (MRI) scans traditionally show the brain in right-to-left reversal. A CT, for example, will show a left cerebral lesion on the right side of the study. Medical illustrations should include a notation to orient the reader.

Optic nerve lesions, such as optic neuritis or trauma, lead to loss of an area of the visual field, scotoma, of the ipsilateral eye. This area is usually oval or kidney-shaped and, unlike most other visual field defects, crosses the midline. If a lesion damages the entire optic nerve, that eye will lose all vision and the patient will have monocular blindness.

Pituitary adenomas, lesions that most often compress the optic chiasm, usually rise upward and disrupt the inferior nasal crossing fibers. The damage to these fibers causes bitemporal superior quadrantanopsia. If adenomas continue to expand and grow upward, they disrupt the superior as well as the inferior crossing fibers. Increased damage to the nasal crossing fibers expands the visual field deficit to a bitemporal hemianopsia.

Injuries anywhere in the optic tract between the optic chiasm, lateral geniculate bodies, or occipital cortex cause contralateral homonymous quadrantanopsias or hemianopsias. For example, strokes in the distribution of the left posterior cerebral artery cause infarctions of the left occipital cortex that result in a right homonymous hemianopsia. Similarly, strokes in the distribution of the left middle cerebral artery cause infarctions of a segment of the optic tract anterior to the occipital lobe, but still cause a right homonymous hemianopsia.

Strokes in the frontal or parietal lobes usually cause physical and neuropsychological deficits in addition to a homonymous hemianopsia. In those strokes, ocular deviation, hemiparesis, hemisensory loss, and certain neuropsychological deficits typically accompany homonymous hemianopsia. For example, right-sided homonymous hemianopsia is often associated with conjugate ocular deviation to the left, right-sided hemiparesis and hemisensory loss, and nonfluent aphasia. Likewise, left-sided homonymous hemianopsia is often associated with conjugate ocular deviation to the right, left-sided hemiparesis and hemisensory loss, and left-sided anosognosia and hemi-inattention (see Chapter 8).

Unlike scotoma from optic nerve lesions and many cases of psychogenic visual loss, homonymous and bitemporal hemianopsias respect the midline. Although occipital lesions sometimes do not involve the center of vision (see later), hemianopsias never drift over the center vertical meridian to affect portions of the other visual field.

A rare but important situation is the homonymous superior quadrantanopia (Fig. 12-10). This visual field deficit may be the only physical manifestation of a contralateral temporal lobe lesion. Thus, it may represent the only interictal physical finding in patients who have complex partial seizures or the residua of a temporal lobectomy for trauma or intractable epilepsy.

FIGURE 12-10 Left, Optic tract fibers sweep from the brainstem’s lateral geniculate body to the occipital lobe’s visual cortex. The tract’s inferior fibers first sweep anteriorly – through the temporal lobe’s anterior tip – before heading posteriorly. These fibers convey visual information from the contralateral superior temporal quadrant. Right, A large lesion or a surgical resection of the left temporal lobe has damaged the inferior optic tracts to produce a contralateral (right) superior quadrantanopsia.

When lesions damage only the occipital lobe, patients also develop a contralateral homonymous hemianopsia, but in several respects these lesions are unique. Unlike with damage of the anterior portion of the optic system, precise determinations of the visual fields in occipital lobe lesions may demonstrate that the center of vision is preserved within the hemianopsia. As though the macula, which transmits the center of vision, were represented bilaterally in the occipital cortex, the preservation of this critical visual area is termed macular sparing. Another distinguishing feature is that no cognitive or other physical defects accompany the homonymous hemianopsia.

Conjugate Eye Movement

In the normal, awake state, cerebral cortex (supranuclear) gaze centers (Fig. 12-11) innervate pontine (nuclear) gaze centers, which, in turn, innervate the nearby oculomotor, trochlear, and abducens cranial nerve nuclei (Fig. 12-12). Both eyes thus normally move together in a coordinated, paired (conjugate) manner. This system allows individuals to look (gaze) laterally, follow (pursue) moving objects, or deliberately shift their attention from one to another object (perform a saccade).

FIGURE 12-11 A, At rest, the eyes are midline because the impulses of each frontal lobe conjugate gaze center are balanced, each “pushing” the eyes contralaterally. Maintaining eyes in one position is an active process. B, Voluntarily increased activity of the left cerebral gaze center drives the eyes to the right (contralateral). C, Similarly, involuntarily increased cerebral activity, as occurs during a seizure, drives the eyes contralaterally. The seizure may also cause right arm and leg tonic-clonic activity. D, A stroke destroys the left cerebral gaze center, permitting the right center to push the eyes toward the lesion. It also destroys the cerebral motor strip, causing contralateral paresis. The eyes “looking” away from the hemiparesis characterize this common stroke.

FIGURE 12-12 When looking to the right, the left frontal conjugate gaze center stimulates the right (contralateral) pontine gaze center, which neurologists also call the pontine paramedian reticular formation (PPRF). The pontine gaze center, in turn, stimulates the right (adjacent) abducens nerve nucleus and, upwards through the left medial longitudinal fasciculus (MLF), the left (contralateral) oculomotor nerve nucleus, which sits in the midbrain (see Fig. 15-3).

When individuals are conscious and looking about, their cortical, supranuclear gaze centers determine their gaze through their conjugate eye movements. When they are unconscious, tested in various ways, or beset by a variety of conditions that injure their cerebral cortex, their pontine, nuclear gaze centers assume control of their conjugate eye movements. In particular, when people dream, pontine centers generate REMs (see REM sleep, Chapter 17). Also, during both oculocephalic testing, in which the head is rocked back and forth, and cold caloric testing, in which neurologists irrigate the otic canals with cold water, labyrinthine stimulation of the pontine centers overrides any supranuclear innervation, and the nuclear stimulation drives the eye movement. In brain death, of course, neither cortical nor brainstem stimulation produces any eye movement.

Conjugate Eye Deviation From Cerebral Lesions

In an alert person, each cerebral conjugate gaze center continuously emits impulses that go through a complicated pathway to “push” the eyes contralaterally. With the counterbalancing activity of each cerebral gaze center, the eyes remain midline (see Fig. 12-11). When a person wants to look to one side, the contralateral cerebral gaze center increases activity. For example, when someone wants to look toward a water glass on the right, the left cerebral gaze center activity increases and, as if pushing the eyes away, both eyes turn to the right. If this person wished to reach for the glass, the left cerebral motor strip, which is situated posterior to the gaze center, would mobilize the right arm.

Partial seizures also increase activity of the cerebral conjugate gaze center. They push the eyes contralaterally and, because the seizures usually encompass the adjacent corticospinal tract, they push the head and neck contralaterally and produce tonic-clonic activity of the contralateral arm and leg (see Fig. 10-7).

In contrast, when patients have unilateral destructive cerebral injuries, such as large strokes, the activity of the gaze center on that side is abolished. The activity of the other center, being unopposed, pushes the eyes toward the injured side. (Neurologists often invoke the adage, “The eyes look toward the [cerebral] stroke.”) For example, with a left cerebral stroke, the eyes deviate toward the left. In addition, because the stroke would also damage the corticospinal tract, the right side of the body would be paralyzed. (Here the saying is, “When the eyes look away from the paralysis, the stroke is cerebral.”)

Damage of the corticobulbar tracts, which innervate the extraocular muscle nuclei, abolishes voluntary conjugate gaze. As the most famous example, progressive supranuclear palsy (PSP) (see Chapter 7) consists of cerebral neurodegeneration that causes parkinsonism, dementia, and the illness’ pathognomonic finding – impairment of vertical and then lateral gaze. Within 3 years of the onset of the illness, PSP patients cannot voluntarily look upward or downward and then later to either side; however, neurologists can overcome the ocular paresis by performing oculocephalic testing (see Fig. 7-10).

Conjugate Eye Deviation From Brainstem Lesions

Each cerebral gaze center normally produces conjugate eye movements by stimulating a contralateral pontine gaze center, which neurologists also call the pontine paramedian reticular formation (PPRF). In contrast to the movement generated by the cerebral center, each pontine center pulls the eyes toward its own side (see Fig. 12-12). A stroke on one side of the pons thus allows the eyes to be pulled toward the opposite side. For example, if a stroke damaged the right pontine gaze center, the eyes would deviate to the left. Also, because this stroke would damage corticospinal tract in the right pons, the left arm and leg would be paralyzed. With a pontine lesion, neurologists say, “The eyes look toward the paralysis.”

When the pontine gaze center receives impulses from the contralateral cerebral conjugate gaze center, it activates one abducens nucleus and the contralateral oculomotor nucleus to produce conjugate lateral eye movement: the adjacent abducens (sixth cranial nerve) nucleus and, through the medial longitudinal fasciculus (MLF), the contralateral oculomotor (third cranial nerve) nucleus (see Figs 15-3 and 15-4). If the brain were to activate both abducens nuclei at the same time, both eyes would turn outward. If it were to stimulate both oculomotor nuclei, both eyes would turn inward.

MLF injury, as often occurs in MS and brainstem strokes, produces the MLF syndrome or internuclear ophthalmoplegia (INO). This condition, which spares the cranial nuclei and nerves, causes a classic pattern of ocular movement impairment identifiable primarily by inability of the eye ipsilateral to the lesion to adduct past the midline (see Chapter 15).

Another important ocular movement abnormality is nystagmus, which usually consists of rhythmic horizontal, vertical, or rotatory oscillations of both eyes. Several CNS injuries, including MS and brainstem strokes, cause nystagmus. In addition, it may be the most prominent physical finding from alcohol or drug intoxication. Physicians should particularly consider Wernicke–Korsakoff syndrome and phencyclidine (PCP) intoxication in delirious patients with nystagmus. On the other hand, neurologists routinely detect nystagmus in epilepsy patients taking therapeutic doses of phenytoin (Dilantin) or phenobarbital. In them, its absence may suggest noncompliance.

Although usually a sign of CNS dysfunction, nystagmus may be a normal variant. For example, many normal individuals have a few beats of horizontal nystagmus when looking far laterally (end-point nystagmus). Some have congenital nystagmus, which may be disconcerting to people looking at them, but it does not interfere with their vision. Congenital nystagmus is usually pendular (no alternation of fast and slow phases), direction-changing, and absent when they look toward a particular point (the null point).

Sometimes nystagmus from labyrinthitis mimics nystagmus from brainstem ischemia. However, in labyrinthitis, vertigo, nausea, and vomiting overshadow the nystagmus.

Saccades and Pursuit Movement

Under ordinary circumstances, when an object enters the periphery of the visual field, the eyes dart toward it to redirect the line of sight and refocus attention. The eyes rotate conjugately, smoothly, and rapidly. Their movement does not disturb the eyelids or move the head. These ocular movements, saccades, are characterized by their rapidity, which may exceed 700°/second.

Neurologists examine saccades by asking patients to stare at an object 45° to one side and then suddenly shift their gaze to an object 45° to the other side. At the bedside, the primary abnormality is slowness. Other abnormalities are overshooting or undershooting (hypermetria and hypometria), irregular or jerky movements, and – a subtle one – initiating the saccade by blinking or a head jerk (Fig. 12-13).

FIGURE 12-13 In testing for saccades, an examiner asks a patient with Huntington disease to shift his gaze from the examiner’s nose (A) to an object 3 feet (90 cm) to the left (B); however, after the patient’s eyes shift conjugately to the left, they jerk momentarily to the right, then resume their leftward movement, but overshoot the target. They finally come to rest on the object. Another characteristic of abnormal saccades is that they may force patients to initiate them by blinking, widely opening their eyelids, or tossing their head in the direction of the desired gaze.

While saccades are responsible for rapid shift of gaze from one object to another, pursuit or smooth pursuit is the slow continual ocular tracking of a single moving object, such as a bird in flight just above the horizon. In other words, unlike saccades, pursuits follow and maintain gaze on an object always in the visual field. The bedside test consists of asking the patient to follow the examiner’s finger as it moves horizontally at about 30°/second. The eyes should remain on the target and smoothly track the finger through a 6-second path. The primary abnormalities would be an irregular rather than a smooth path and jerky velocity. Numerous lesions and illnesses – even fatigue and inattention – impair smooth pursuit (Box 12-3).

Many conditions, including strokes, MS, tumors, neurodegenerative illnesses, and schizophrenia, can damage the intricate mechanisms that generate these movements. The responsible lesions may be located in the cerebral cortex, cerebellum, pons, or occasionally elsewhere in the CNS. Abnormal saccades are a signature of Huntington disease (see Chapter 18).

Abnormalities in smooth pursuit and, and less so, saccades characterize eye movements of schizophrenic patients and even some of their asymptomatic first-degree relatives. The abnormalities occur independently of medications. Similar abnormalities are also present, although less frequently, in individuals with depression, borderline personality disorder, and other psychiatric disturbances. Notably, in depression, they improve with successful treatment.

Diplopia

Monocular diplopia is usually the result of either ocular abnormalities, such as a dislocated lens, or psychogenic factors. In either case, it persists in all directions of gaze, and covering the affected eye should abolish it.

The form of diplopia most characteristic of a neurologic disorder – binocular diplopia – results from misalignment of the two eyes. Unlike monocular diplopia, it is usually present only in certain directions of gaze and covering either eye will abolish it.

The neurologic causes of diplopia are almost always lesions in the brainstem or lower in the neurologic hierarchy: INO and other brainstem syndromes; oculomotor, trochlear, or abducens cranial nerve injury; neuromuscular junction disorders; or extraocular muscle paresis. In contrast, lesions above the brainstem, such as cerebral and other supranuclear lesions, characteristically cause conjugate gaze palsies, but not diplopia.

Oculomotor (third cranial) nerve injury results in diplopia that is greatest when the patient looks laterally. The three findings that neurologists rely on when attributing diplopia on lateral gaze to a third nerve injury are ptosis, lateral deviation of the eye, and a dilated pupil (Fig. 12-14). With third nerve palsy, diplopia will be most pronounced when the patient attempts to adduct the eye, i.e., bring it medially. For example, a patient with damage to the left oculomotor nerve will have difficulty adducting the left eye, and diplopia will be greatest upon looking to the right. Physicians should know that third nerve infarction from diabetes represents an important variation. While having all the other deficits of a third nerve palsy, a third nerve infarction from diabetes “spares the pupil,” i.e., the pupil remains reactive to light and the same size as its counterpart. Diabetic infarctions of the third nerve are also often painful.

FIGURE 12-14 In the center picture, a patient with a left oculomotor (third cranial) nerve palsy looks straight ahead. The left upper lid is lower, the pupil larger, and the eye deviated slightly laterally. Because the eyes are dysconjugate, the patient sees two arrows (diplopia) when looking ahead. In the picture on the left, the patient looks to the right. Because the paretic left eye fails to cross medially beyond the midline (i.e., it fails to adduct), the eyes are more dysconjugate and there is greater diplopia. In the picture on the right, the patient looks to the left. The eyes are almost conjugate and there is little or no diplopia.

Abducens (sixth cranial) nerve injury also causes diplopia on looking laterally. In contrast to a third nerve palsy, the examination finds medial deviation of the affected eye at rest and inability of that eye to abduct. Also in contrast to a third nerve palsy, the examination shows neither ptosis nor pupil dilation (Fig. 12-15).

FIGURE 12-15 In the center picture, a patient with a left abducens (sixth cranial) nerve palsy looks straight ahead. The patient’s left eye is deviated medially. The eyes are dysconjugate, and the patient sees two arrows when looking ahead. In the picture on the left, the patient looks to the right. The eyes are conjugate, and the patient sees only a single arrow. In the picture on the right, the patient looks to the left. The paretic left eye fails to cross the midline laterally, that is, it fails to abduct. The exaggeration of the dysconjugate gaze increases the diplopia.

When myasthenia gravis, the classic neuromuscular junction disorder, causes diplopia, patients have fluctuating, variable, and asymmetric combinations of ptosis and paresis of various ocular muscles. However, no matter how severe the diplopia and ptosis, patients’ pupils are characteristically round, equal, and reactive to light (see Chapter 6).

Although congenital ocular muscle weakness, strabismus, causes dysconjugate gaze, children and adults with strabismus do not have diplopia because the brain suppresses the image from the weaker eye. With continuous suppression of vision from one eye, that eye will lose vision and become blind (i.e., amblyopic). Thus, ophthalmologists patch the “good” eye of babies and children with strabismus for several hours each day. The patching forces them to use the weakened eye, which strengthens its visual and systems muscles. Alternatively, ophthalmologists perform muscle surgery or administer intramuscular botulinum toxin injections to re-establish conjugate gaze and thereby bring the affected eye into play.

Mitochondrial myopathies, such as progressive external ophthalmoplegia, may particularly affect the extraocular muscles because of their delicate nature and high metabolic demands (see Chapter 6). These disorders cause extraocular muscle paresis, including prominent ptosis, and sometimes diplopia. Although the paresis may mimic myasthenia gravis, mitochondrial myopathies progress insidiously, do not fluctuate, symmetrically weaken muscles, and usually spare facial, vocal, and limb muscles.

Psychogenic factors may also be responsible for symptoms of diplopia. However, before diagnosing psychogenic diplopia, physicians must not overlook subtle neurologic conditions, especially myasthenia gravis and the MLF syndrome. Psychogenic diplopia is usually intermittent, inconsistent, and present in all directions of gaze. As previously discussed, sometimes the diplopia is monocular. Patients with psychogenic diplopia, of course, have no observable abnormality. A common set of tests consists of the patient reading colored or polarized charts using colored or polarized lenses.

Horner Syndrome and Argyll Robertson Pupils

Contrary to a reasonable expectation that the brain would innervate eye muscles through short and direct pathways, the sympathetic tract follows a remarkably long and circuitous route (Fig. 12-16, A). Injury to the sympathetic tract leads to Horner syndrome: ptosis, miosis (a small pupil), and anhidrosis (lack of sweating) (Fig. 12-16, B). Given the vulnerability of injury during its long route, sympathetic tract damage leading to Horner syndrome can result from any of several widely separate injuries, including lateral medullary infarction (see Wallenberg syndrome; Fig. 2-10); cervical spinal cord injury; apical lung (Pancoast) tumor; and, because of a carotid artery dysfunction, cluster headache (see Fig. 9-4).

FIGURE 12-16 A The sympathetic nervous system originates in the hypothalamus, passes caudally through the brainstem, and descends further – into the cervical and then the uppermost thoracic spinal cord. Some sympathetic system neurons leave the thoracic spinal cord and, after making a hairpin turn, ascend to form ganglia adjacent to the cervical vertebrae. These postsynaptic neurons ascend further by successively wrapping themselves around the common carotid and then internal carotid arteries until they enter the orbit with the ophthalmic division of the trigeminal nerve (V₁). Through these postsynaptic neurons, the sympathetic nervous system innervates the pupil dilator muscles, upper eyelid muscles, and facial sweat glands. B Top, Sympathetic nervous system activity retracts the eyelid, dilates the pupil, and causes sweating. These cardinal signs of the fight or flight response may also be induced by states of excitement, including amphetamine use. Bottom, Interruption of the sympathetic tract injury causes Horner syndrome – ptosis, miosis, and anhidrosis – on this patient’s left side. A subtle clue to Horner syndrome ptosis is the eyebrow elevation, which is an unconscious contraction of upper facial muscles to uncover the pupil.

Physicians might confuse Horner syndrome with a third nerve injury because ptosis is a manifestation common to both conditions. However, the Horner syndrome’s small pupil readily separates it from a third nerve injury, which causes a dilated, unreactive pupil. Anhidrosis in Horner syndrome is another clue, but one that is difficult to detect. As a diagnostic test, physicians might instill eyedrops of apraclonidine, which is a weak alpha-adrenergic stimulant. It will briefly dilate the pupil and retract the eyelid in Horner syndrome.

In a different situation, the astute physician confronting a small pupil must also bear in mind that the real problem may be that the contralateral one is abnormally large. Causes of a dilated pupil include lesions that damage the parasympathetic supply of the pupil sphincter muscles, as well as an oculomotor nerve injury, because lack of parasympathetic innervation leaves the sympathetic innervation unopposed. An acquired benign variation, Adie pupil, exemplifies the pupil-dilating effect of depriving a pupil of its normal parasympathetic innervation (Fig. 12-17).

FIGURE 12-17 Top, The parasympathetic innervation of the pupil sphincter muscle, which constricts the pupil, originates in the Edinger–Westphal nucleus (see Fig. 4-2). That nucleus, adjacent to the third cranial (oculomotor) nerve nucleus, sends its parasympathetic fibers along with the oculomotor nerve. The parasympathetic fibers then separate and synapse in the parasympathetic ciliary ganglion. From there, postsynaptic fibers form a neuromuscular junction with the sphincter muscles. Acetylcholine (ACh) is the neurotransmitter in both synapses. Through this pathway, light and various other stimuli cause pupil constriction. Bottom, In the Adie pupil, which is typically a unilateral condition, the ciliary ganglion degenerates and the pupil, deprived of parasympathetic innervation, dilates. The loss of the ciliary ganglia also subjects the pupil to denervation hypersensitivity. In this case, the left (Adie) pupil suffers from a congenital impairment of the ciliary ganglion. Without the parasympathetic innervation, the left pupil dilates at rest in room light. In response to bright light, it would constrict only weakly, incompletely, and slowly. Diluted cholinergic eyedrops (0.1% pilocarpine), which have no effect on normal pupils, including this patient’s unaffected right eye, produce a brisk and long-lasting constriction of the Adie pupil. The reaction is exaggerated in the Adie pupil because its denervated postsynaptic neurons are overly sensitive, i.e., have denervation hypersensitivity. Normal pupils as well as the Adie pupil will constrict when physicians apply a more concentrated solution of pilocarpine (1%). As a surprising, seemingly unrelated, comorbidity of Adie pupil, patients often lose their quadriceps and Achilles deep tendon reflexes.

In yet another example, accidentally rubbing atropine-like substances into the affected eye can cause a dilated pupil. In a notorious variant, which is a manifestation of Factitious Disorder, individuals – often medical personnel – surreptitiously instill eyedrops containing pupil-dilating substances. The unilateral dilated pupil typically triggers hospitalization and a series of investigations.

Argyll Robertson pupils, which differ in subtle ways from those with other injuries, are irregular, asymmetric, and small (1–2 mm). They characteristically constrict normally when patients look at closely held objects (i.e., during accommodation), but fail to react to light. The intact accommodation, but impaired light reflex, especially with the historic association with syphilis, has given rise to the simile, “Argyll Robertson pupils are like prostitutes. They accommodate but do not react.” Today’s statistics belie that statement: Diabetic autonomic neuropathy and cataract surgery currently cause almost all cases of Argyll Robertson pupils.

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