Disorders that affect the ocular muscles, ocular motor (III, IV, and VI) cranial nerves, or visual or ocular motor pathways in the brain produce a wide variety of neuro-ophthalmic disturbances. Because the anatomic pathways of the visual and ocular motor systems traverse major portions of the brainstem and cerebral hemispheres, neuro-ophthalmic symptoms and signs are often valuable in the anatomic localization and diagnosis of neurologic disease.
FUNCTIONAL ANATOMY OF THE VISUAL SYSTEM
Visual information enters the nervous system when light, refracted and focused by the lens, creates a visual image on the retina at the back of the eye (Figure 7-1). The action of the lens causes this image to be reversed in the horizontal and vertical planes. Thus, the superior portion of the visual image falls on the inferior retina and vice versa, and the temporal (lateral) and nasal (medial) fields are likewise reversed (Figure 7-2). The center of the visual field is focused at the fovea, where the retina’s perceptual sensitivity is greatest. Within the retina, photoreceptor cells (rods and cones) transduce incident light into neuronal impulses, which are transmitted by retinal neurons to the optic (II) nerve. At this and all other levels of the visual system, the topographic relations of the visual field are preserved.
Representation of the visual field at the level of the retina: the point of fixation is focused on the fovea, the physiologic blind spot on the optic disk, the temporal half of the visual field on the nasal side of the retina, and the nasal half of the visual field on the temporal side of the retina.
Representation of the visual field at the level of the optic nerve, chiasm, and optic tract. Quadrants of the visual field are designated ST (superior temporal), IT (inferior temporal), SN (superior nasal), and IN (inferior nasal).
PERIPHERAL VISUAL PATHWAYS
Each optic nerve contains fibers from one eye, but the nasal (medial) fibers, conveying information from the temporal (lateral) visual fields, cross in the optic chiasm (see Figures 1-13 and 7-2). As a result, each optic tract contains fibers not from one eye, but from one-half of the visual fields of both eyes. Because of this arrangement, prechiasmal lesions affect vision in the ipsilateral eye and retrochiasmal lesions produce defects in the contralateral half of the visual field of both eyes (see Figure 1-13).
The optic tracts terminate in the lateral geniculate nuclei, synapsing on neurons that project through the optic radiations to the primary visual or calcarine cortex (area 17), located near the posterior poles of the occipital lobes, and visual association areas (areas 18 and 19). Here, too, the visual image is represented in such a way that its topographic organization is preserved (Figure 7-3). The central region of the visual field (macula) is represented in the most posterior portion of the visual cortex, whereas the inferior and superior parts of the field (superior and inferior retina) are represented above and below the calcarine fissure, respectively.
Representation of the visual field at the level of the primary visual cortex, midsagittal view, shows the medial surface of the right occipital lobe, which receives visual input from the left side of the visual field of both eyes.
VASCULAR SUPPLY OF VISUAL PATHWAYS
The vascular supply of the visual system is derived from the ophthalmic, middle cerebral, and posterior cerebral arteries (Figure 7-4); ischemia or infarction in the territory of any of these vessels can produce visual field defects.
Arterial supply of the visual system, viewed from below.
Retina—The retina is supplied by the central retinal artery, a branch of the ophthalmic artery, which is itself a branch of the internal carotid artery. Because the central retinal artery subsequently divides into superior and inferior retinal branches, vascular disease of the retina tends to produce altitudinal (ie, superior or inferior) visual field deficits.
Optic nerve—The optic nerve receives arterial blood primarily from the ophthalmic artery and its branches.
Optic radiations—As the optic radiations course backward toward the visual cortex, they are supplied by branches of the middle cerebral artery. Ischemia or infarction in the distribution of the middle cerebral artery may thus cause loss of vision in the contralateral visual field (see Figure 7-7).
Primary visual cortex—The primary visual cortex is supplied principally by the posterior cerebral artery. Occlusion of one posterior cerebral artery produces blindness in the contralateral visual field, although the dual (middle and posterior cerebral) arterial supply to the macular region of the visual cortex may spare central (macular) vision. Because the left and right posterior cerebral arteries arise together from the basilar artery, occlusion at the tip of the basilar artery can cause bilateral occipital infarction (see figure 7-4) and complete cortical blindness—although, in some cases, macular vision is spared.
FUNCTIONAL ANATOMY OF THE OCULAR MOTOR SYSTEM
Movement of the eyes is accomplished by the action of six muscles attached to each globe (Figure 7-5). These muscles act to move the eye into each of six cardinal positions of gaze. Equal and opposed actions of these six muscles in the resting state place the eye in mid- or primary position, that is, looking directly forward. When the function of one extraocular muscle is disrupted, the eye is unable to move in the direction of action of the affected muscle (ophthalmoplegia) and may deviate in the opposite direction because of the unopposed action of other extraocular muscles. When the eyes are thus misaligned, visual images of perceived objects fall on a different region of each retina, creating the illusion of double vision, or diplopia.
Anatomy and function of extraocular muscles. (A) Extraocular muscles in the left orbit (lateral view). (B) An illustration of the right eye viewed from above in the primary position (center figure) showing the angle of attachment of the superior and inferior rectus muscles and the superior and inferior oblique muscles. With the eye directed to the right, the superior and inferior rectus muscles can now be examined as pure elevators and depressors of the globe (right image), and with the eye deviated to the left, the oblique muscles can now be examined as pure elevators and depressors of the globe as illustrated in C. (C) The six cardinal positions of gaze for testing eye movement. The eye is adducted by the medial rectus and abducted by the lateral rectus. The adducted eye is elevated by the inferior oblique and depressed by the superior oblique; the abducted eye is elevated by the superior rectus and depressed by the inferior rectus.
The extraocular muscles are innervated by the oculomotor (III), trochlear (IV), and abducens (VI) nerves. Because of this differential innervation of the ocular muscles, the pattern of their involvement in pathologic conditions can help to distinguish a disorder of the ocular muscles from a disorder that affects a cranial nerve. Cranial nerves that control eye movement traverse long distances to pass from the brainstem to the eye; they are thereby rendered vulnerable to injury by a variety of pathologic processes.
Oculomotor (III) nerve—The oculomotor nerve supplies the medial rectus, superior and inferior rectus, and inferior oblique muscles and carries fibers to the levator palpebrae (which raises the eyelid). It also supplies the parasympathetic fibers responsible for pupillary constriction. With a complete nerve III lesion, the eye is partially abducted, and cannot be adducted elevated, and depressed; the eyelid droops (ptosis), and the pupil is nonreactive.
Trochlear (IV) nerve—The trochlear nerve innervates the superior oblique muscle. Lesions of this nerve result in defective depression of the adducted eye.
Abducens (VI) nerve—Lesions of the abducens nerve cause lateral rectus palsy, with impaired abduction of the affected eye.
The nuclei of the oculomotor (III) and trochlear (IV) nerves are located in the dorsal midbrain, ventral to the cerebral aqueduct (of Sylvius), whereas the abducens (VI) nerve nucleus occupies a similarly dorsal and periventricular position in the pons. Lesions involving these nuclei give rise to clinical abnormalities similar to those produced by involvement of their respective cranial nerves; in some cases, nuclear and nerve lesions can be distinguished.
Oculomotor (III) nerve nucleus—Although each oculomotor nerve supplies muscles of the ipsilateral eye only, fibers to the superior rectus originate in the contralateral oculomotor nerve nucleus, and the levator palpebrae receives bilateral nuclear innervation. Thus, ophthalmoplegia affecting only one eye with ipsilateral ptosis or superior rectus palsy suggests oculomotor nerve disease, whereas ophthalmoplegia with bilateral ptosis or contralateral superior rectus palsy is probably due to a nuclear lesion.
Trochlear (IV) nerve nucleus—It is not possible to distinguish clinically between lesions of the trochlear nerve (see earlier) and those of its nucleus.
Abducens (VI) nerve nucleus—In disorders affecting the abducens nerve nucleus (rather than the nerve itself), lateral rectus paresis is often associated with facial weakness, paresis of ipsilateral conjugate gaze, or a depressed level of consciousness. This is because of the proximity of the abducens nerve nucleus to the facial (VII) nerve fasciculus, pontine lateral gaze center, and ascending reticular activating system, respectively. When a Horner syndrome (miosis of the pupil, ptosis, and sometimes segmental anhidrosis) accompanies an abducens nerve palsy, the lesion is in the cavernous sinus.
SUPRANUCLEAR CONTROL OF EYE MOVEMENTS
Supranuclear control of eye movements enables the two eyes to act in concert to produce version (conjugate gaze) or vergence (convergence and divergence) movements.
Brainstem gaze centers—Centers that control horizontal (lateral) and vertical gaze are located in the pons and pretectal region of the midbrain, respectively, and receive descending inputs from the cerebral cortex that allow voluntary control of gaze (Figure 7-6). Each lateral gaze center, located in the paramedian pontine reticular formation (PPRF) adjacent to the abducens nerve nucleus, mediates ipsilateral, conjugate, horizontal gaze via its connections to the ipsilateral abducens (VI) and contralateral oculomotor (III) nerve nucleus. A lesion in the pons affecting the PPRF therefore produces a gaze preference away from the side of the lesion and toward the side of an associated hemiparesis, if present. Disorders of vertical gaze, typically impaired upgaze, may result from mass lesions that exert downward pressure on the dorsal midbrain, such as pineal tumors (Parinaud syndrome).
Cortical input—The PPRF receives cortical input from the contralateral frontal lobe, which regulates rapid eye movements (saccades), and from the ipsilateral parietooccipital lobe, which regulates slow eye movements (pursuits). Therefore, a destructive lesion affecting the frontal cortex interferes with the mechanism for contralateral horizontal gaze and may result in a gaze preference toward the side of the lesion (and away from the side of associated hemiparesis). By contrast, an irritative (seizure) focus in the frontal lobe may cause gaze away from the side of the focus.
Neuronal pathways involved in horizontal gaze.
The first step is to obtain a clear description of the complaint. Patients may only complain of vague symptoms, such as blurred vision, which provide little diagnostic information. Therefore, it is important to determine whether the patient means to describe decreased visual acuity in one or both eyes, loss of vision in part of the visual field, diplopia, an unstable visual image, pain in or about the eye, or some other problem.
TEMPORAL PATTERN OF SYMPTOMS
Once the nature of the complaint has been established, inquiries regarding its temporal pattern can provide clues to the underlying pathologic process:
Sudden onset—Vascular disorders that affect the eye or its connections in the brain tend to produce symptoms of sudden onset.
Slow onset—With inflammatory or neoplastic disease, symptoms usually evolve over a longer period.
Transient, recurrent symptoms—Transient and recurrent symptoms suggest a select group of pathologic processes, including intermittent ischemia, multiple sclerosis, and myasthenia gravis.
ASSOCIATED NEUROLOGIC ABNORMALITIES
The nature of any associated neurologic abnormalities, such as impaired facial sensation, weakness, ataxia, or aphasia, can help in localizing the site of involvement.
The history should be scrutinized for conditions that predispose the patient to neuro-ophthalmic problems as follows:
Multiple sclerosis often involves the optic nerve or brainstem, leading to a variety of neuro-ophthalmic disorders. A history of disturbances that also involve other parts of the central nervous system should suggest this diagnosis.
Atherosclerosis, hypertension, and diabetes can be complicated by vascular disorders of the eye, cranial nerves, or visual or ocular motor pathways in the brain.
Endocrine disorders (eg, hyperthyroidism) can cause ocular myopathy.
Connective tissue disease and systemic cancer can affect the visual and ocular motor systems at a variety of sites in the brain or subarachnoid space.
Nutritional deficiencies may present with neuro-ophthalmic symptoms, as in the amblyopia (decreased visual acuity) associated with malnutrition and the ophthalmoplegia of Wernicke encephalopathy (thiamine deficiency).
Drugs (eg, ethambutol, isoniazid, digitalis, clioquinol) may be toxic to the visual system, and others (sedative drugs, anticonvulsants) commonly produce ocular motor disorders.
To identify neuro-ophthalmic problems, vision should be tested under conditions that eliminate refractive errors. Therefore, patients should be examined wearing their spectacles (a pinhole can be substituted if the corrective lenses usually worn are not available at the time of testing). Visual acuity must be assessed for each eye separately. Distant vision is tested using a Snellen eye chart, with the patient 6 m (20 ft) away. Near vision is tested with a Rosenbaum pocket eye chart held approximately 36 cm (14 in) from the patient. In each case, the smallest line of print that can be read is noted.
Visual acuity is expressed as a fraction (eg, 20/20, 20/40, 20/200). The numerator is the distance (in feet) from the test figures at which the examination is performed, and the denominator is the distance (in feet) at which figures of a given size can be correctly identified by persons with normal vision. For example, if a patient standing 20 ft away from the eye chart is unable to identify figures that can normally be seen from that distance but can identify the larger figures that would be visible 40 ft away with normal acuity, the visual acuity is recorded as 20/40. If the patient can read most of a given line but makes some errors, acuity may be recorded as 20/40–1, for example, indicating that all but one letter on the 20/40 line were correctly identified. When visual acuity is markedly reduced, it can still be quantified, though less precisely, by the distance at which the patient can count fingers (CF), discern hand movement (HM), or perceive light. If an eye is totally blind, the examination will reveal no light perception (NLP).
Red–green color vision is often disproportionately impaired in optic nerve lesions and can be tested with colored objects such as pens or hatpins or with color vision plates.
Evaluating the visual fields can be a lengthy and tedious procedure if conducted in an undirected fashion. Familiarity with the common types of visual field defects is important if testing is to be reasonably rapid and yield useful information. The most common visual field abnormalities are illustrated in Figure 7-7.
Common visual field defects and their anatomic bases. 1. Central scotoma caused by inflammation of the optic disk (optic neuritis) or optic nerve (retrobulbar neuritis). 2. Total blindness of the right eye from a complete lesion of the right optic nerve. 3. Bitemporal hemianopia caused by pressure exerted on the optic chiasm by (for example) a pituitary tumor. 4. Right nasal hemianopia caused by a perichiasmal lesion (eg, calcified internal carotid artery). 5. Right homonymous hemianopia from a lesion of the left optic tract. 6. Right homonymous superior quadrantanopia caused by partial involvement of the optic radiation by a lesion in the left temporal lobe (Meyer loop). 7. Right homonymous inferior quadrantanopia caused by partial involvement of the optic radiation by a lesion in the left parietal lobe. 8. Right homonymous hemianopia from a complete lesion of the left optic radiation. (A similar defect may also result from lesion 9.) 9. Right homonymous hemianopia (with macular sparing) resulting from posterior cerebral artery occlusion.
The normal monocular visual field subtends an angle of approximately 160 degrees in the horizontal plane and approximately 135 degrees in the vertical plane. With binocular vision, the horizontal range of vision exceeds 180 degrees.
Within the normal field of each eye is a 5-degree blind spot, corresponding to the optic disk, which lacks receptor cells. The blind spot is located 15 degrees temporal to fixation in each eye.
Like visual acuity, the visual field must be examined separately for each eye as described below:
Confrontation (Figure 7-8) is the simplest method for visual field testing. The examiner stands at about arm’s length from the patient, with the eyes of both patient and examiner aligned in the horizontal plane. The eye not being tested is covered by the patient’s hand or an eye patch. The examiner closes the eye opposite the patient’s covered eye, and the patient is instructed to fix on the examiner’s open eye. Now the monocular fields of patient and examiner are superimposed, which allows comparison of the patient’s field with the examiner’s presumably normal field. The examiner uses the index fingers of either hand to locate the boundaries of the patient’s field, moving them slowly inward from the periphery in all directions until the patient detects them. The boundaries are then defined more carefully by determining the farthest peripheral sites at which the patient can detect slight movements of the fingertips or the white head of a pin. The patient’s blind spot can be located in the region of the examiner’s own blind spot, and the sizes of these spots can be compared using a pin with a white head as the target. The procedure is then repeated for the other eye.
Subtle field defects may be detected by asking the patient to compare the brightness of colored objects presented at different sites in the field or by measuring the fields using a pin with a red head as the target.
In young children, the fields may be assessed by standing behind the child and bringing an attention-getting object, such as a toy, forward around the child’s head in various directions until it is first noticed.
A gross indication of visual field abnormalities may be obtained in obtunded patients by determining whether they blink in response to a visual threat—typically the examiner’s finger—brought toward the patient’s eye in various regions of the field.
Although many visual field deficits are detectable by these screening procedures, more precise mapping of the fields requires the use of standard tangent screen testing or automated perimetry techniques.
Confrontation testing of the visual field. (A) The left eye of the patient and the right eye of the examiner are aligned. (B) Testing the superior nasal quadrant. (C) Testing the superior temporal quadrant. (D) Testing the inferior nasal quadrant. (E) Testing the inferior temporal quadrant. The procedure is then repeated for the patient’s other eye.
Ophthalmoscopy of the optic fundus is particularly important for evaluating disorders that affect the retina or optic disk and examining patients with a suspected increase in intracranial pressure.
Preparation of the Patient
The examination should be conducted in a dark room so that the pupils are dilated; in some patients, the use of mydriatic (sympathomimetic or anticholinergic) eye drops is necessary. In the latter case, visual acuity and pupillary reflexes should be assessed before instilling the drops. Mydriatic agents should be avoided in patients with untreated closed-angle glaucoma, and in situations—such as impending or ongoing transtentorial herniation—in which the state of pupillary reactivity is an important guide to management.
Examination of the Fundus
Familiarity with the normal appearance of the optic fundus (see Figure 1-10) is necessary if abnormalities are to be appreciated.
Normal appearance—The optic disk is usually easily recognizable as a yellowish, slightly oval structure situated nasally at the posterior pole of the eye (Figure 1-10). The temporal side of the disk is often paler than the nasal side. The disk margins should be sharply demarcated, though the nasal edge is commonly less distinct than the temporal edge. The disk is normally in the same plane as the surrounding retina. Blood vessels crossing the border of the optic disk are distinct and pulsatile and become obscured when the disk swells.
Optic disk swelling—Optic nerve swelling due to papilledema implies increased intracranial pressure and must be differentiated from swelling due to other causes, such as local inflammation (papillitis) and ischemic optic neuropathy. Papilledema is almost always bilateral, does not typically impair vision (except for enlargement of the blind spot), and is not associated with eye pain. Papilledema can be simulated by disk abnormalities such as drusen (colloid or hyaline bodies).
Increased intracranial pressure is thought to cause papilledema by blocking axonal transport in the optic nerve. Because the optic nerve sheath communicates with the subarachnoid space, disorders associated with increased intracranial pressure that also obstruct the subarachnoid space, such as meningitis, are less likely to cause papilledema. The ophthalmoscopic changes in papilledema typically develop over days or weeks but may become apparent within hours after a sudden increase in intracranial pressure—as, for example, after intracranial hemorrhage. In early papilledema (see Figure 1-11), the retinal veins appear engorged and spontaneous venous pulsations are absent. The disk may be hyperemic, and linear hemorrhages may be seen at its borders. The disk margins become blurred, with the temporal edge last to be affected. In fully developed papilledema, the optic disk is elevated above the plane of the retina, and blood vessels crossing the border of the disk become obscured.
Optic disk pallor—Optic disk pallor with impaired visual acuity, visual field defects, or loss of pupillary reactivity is associated with a wide variety of disorders that affect the optic nerve, including inflammatory conditions, nutritional deficiencies, and degenerative diseases. A pale optic disk with normal visual function can also occur as a congenital variant, and an optic disk may appear artificially pale if a cataract has been removed.
The caliber of the retinal arteries and veins should be observed where they arise from the disk and pass over its edges onto the retina. Features to note include whether these vessels are easily visible throughout their course, whether they appear engorged, and whether spontaneous venous pulsations (which indicate normal intracranial pressure) are present. The remainder of the visible retina is inspected, noting the presence of hemorrhages, exudates, or other abnormalities.
The macula, a somewhat paler area than the rest of the retina, is located approximately two disk diameters temporal to the temporal margin of the optic disk. It can be visualized quickly by having the patient look at the light from the ophthalmoscope. Ophthalmoscopic examination of the macula can reveal abnormalities related to visual loss from age-related macular degeneration, macular holes, or hereditary cerebromacular degenerations.
The size and reactivity of the pupils reflect the integrity of neuronal pathways from the optic nerve to the midbrain (Figure 7-9). The normal pupil is round, regular, and centered within the iris; its size varies with age and with the intensity of ambient light. In a brightly illuminated room, the diameter of normal pupils is approximately 3 mm in adults, smaller in the elderly, and greater than or equal to 5 mm in children. Pupil size may be asymmetric in up to 20% of people (physiologic anisocoria), but the difference is less than or equal to 1 mm. Symmetrically rapid constriction of the pupils in bright light indicates that pupillary function is normal and excludes oculomotor (III) nerve compression.
Anatomic basis of the pupillary light reflex. The afferent visual pathways from the retina to the pretectal nuclei of the midbrain are represented by dashed lines and the efferent pupilloconstrictor pathways from the midbrain to the pupillary constrictor muscles by solid lines. Note that illumination of one eye results in bilateral pupillary constriction.
Direct (ipsilateral) and consensual (contralateral) pupillary constriction in response to a bright light shone in one eye demonstrates the integrity of the pathways shown in Figure 7-9. Normally, the direct response to light is slightly brisker and more pronounced than the consensual response.
Reaction to Accommodation
When the eyes converge to focus on a nearer object (accommodation), the pupils normally constrict. This reaction is tested by having the patient focus alternately on a distant object and a finger held just in front of the nose.
Unilateral disorders of pupillary constriction are seen with local disease of the iris (trauma, iritis, glaucoma), oculomotor (III) nerve compression (tumor, aneurysm), administration of a mydriatic agent, and optic nerve disorders (optic neuritis, multiple sclerosis).
B. Light-Near Dissociation
Impaired pupillary reactivity to light with preserved constriction during accommodation (light-near dissociation) is usually bilateral and may result from neurosyphilis, diabetes, optic nerve disorders, and tumors compressing the midbrain tectum.
C. Argyll Robertson Pupils
These pupils are small, poorly reactive to light, often irregular in shape, and frequently unequal in size; they show light-near dissociation. Neurosyphilis is the classic cause, but other lesions in the region of the Edinger-Westphal nucleus (eg, multiple sclerosis) are now more common (Table 7-1).
Table 7-1.Common Pupillary Abnormalities. ||Download (.pdf) Table 7-1. Common Pupillary Abnormalities.
| ||Appearance ||Response ||Differential Diagnosis |
|Tonic (Adie) pupil ||Unilateral (rarely bilateral) dilated pupil ||Reacts sluggishly and only to persistent bright light or 0.125% pilocarpine eye drops; accommodation less affected ||Holmes–Adie syndrome, ocular trauma, autonomic neuropathy |
|Horner syndrome ||Unilateral small pupil and slight ptosis ||Normal response to light and accommodation ||Lateral medullary infarcts, cervical cord lesions, pulmonary apical or mediastinal tumors, neck trauma or masses, carotid artery dissection or thrombosis, intrapartum brachial plexus injury, cluster headache |
|Argyll Robertson pupil ||Unequal irregular pupils <3 mm in diameter (usually bilateral) ||Poorly reactive to light; more responsive to accommodation ||Neurosyphilis; mimicked by diabetes, pineal region tumors, multiple sclerosis |
The tonic (Adie) pupil (Table 7-1) is larger than the contralateral unaffected pupil and reacts sluggishly to changes in both illumination and accommodation. Because the tonic pupil does eventually react, anisocoria becomes less marked during the examination. This abnormality is most commonly a manifestation of a benign, often familial disorder that frequently affects young women (Holmes–Adie syndrome) and may be associated with depressed deep tendon reflexes (especially in the legs), segmental anhidrosis (localized lack of sweating), orthostatic hypotension, or cardiovascular autonomic instability. Adie pupils may be bilateral. The pupillary abnormality may be caused by degeneration of the ciliary ganglion, followed by aberrant reinnervation of the pupilloconstrictor muscles.
Horner syndrome (Tables 7-1 and 7-2) results from a lesion of the central or peripheral sympathetic nervous system and consists of a small (miotic) pupil associated with mild ptosis (Figure 7-10) and sometimes loss of sweating (anhidrosis).
Table 7-2.Causes of Horner Syndrome. ||Download (.pdf) Table 7-2. Causes of Horner Syndrome.
Central (first) neuron
Hypothalamic region tumor, hemorrhage or infarction
Preganglionic (second) neuron
Thoracic or neck tumor (Pancoast tumor, schwannoma, neuroblastoma, thyroid)
Trauma or surgery (neck, thorax)
Vascular (jugular ectasia, subclavian artery aneurysm)
Postganglionic (third) neuron
Base of skull, parasellar, orbital, or cavernous sinus* mass
Vascular (fibromuscular dysplasia, carotid dissection*)
|Unknown cause ||15% |
(A) Right Horner syndrome after direct carotid puncture for arterial injection. (B) Oculosympathetic pathway involved in Horner syndrome. This three-neuron pathway projects from the hypothalamus to the intermediolateral column of the spinal cord, then to the superior cervical (sympathetic) ganglion, and finally to the pupil, smooth muscle of the eyelid, and sweat glands of the forehead and face.
Oculosympathetic pathways—The sympathetic pathway controlling pupillary dilation consists of an uncrossed three-neuron arc: hypothalamic neurons, which descend through the brainstem to the intermediolateral column of the spinal cord at the T1 level, preganglionic sympathetic neurons projecting from the spinal cord to the superior cervical ganglion, and postganglionic sympathetic neurons that originate in the superior cervical ganglion, ascend in the neck along the internal carotid artery, and enter the orbit with the first (ophthalmic) division of the trigeminal (V) nerve. Horner syndrome is caused by interruption of these pathways at any site (Figure 7-10).
Clinical features—The lesions and resulting pupillary abnormality are usually unilateral. The pupil diameter on the involved side is typically reduced by 0.5 to 1 mm compared with the normal side. This inequality is most marked in dim illumination. The pupillary abnormality is accompanied by mild to moderate ptosis (see later) of the upper lid (as opposed to the pronounced ptosis seen with oculomotor nerve lesions), often associated with elevation of the lower lid (lower lid ptosis). When Horner syndrome has been present since infancy, the ipsilateral iris is lighter and blue (heterochromia iridis).
Deficits in the pattern of sweating, which are most prominent in acute-onset Horner syndrome, can help localize the lesion. If sweating is decreased on an entire half of the body and face, the lesion is in the central nervous system. Cervical lesions produce anhidrosis of the face, neck, and arm only. Sweating is unimpaired if the lesion is above the bifurcation of the carotid artery. The differential diagnosis of Horner syndrome is presented in Table 7-2.
F. Relative Afferent Pupillary Defect (Marcus Gunn Pupil)
The involved pupil constricts less markedly in response to direct illumination than to illumination of the contralateral pupil, whereas normally the direct response is greater than the consensual response. The abnormality is detected by rapidly moving a bright flashlight back and forth between the eyes while continuously observing the suspect pupil (Gunn pupillary test). Relative afferent pupillary defect is commonly associated with disorders of the ipsilateral optic nerve, which interrupt the afferent limb and affect the pupillary light reflex (see Figure 7-9). Such disorders also commonly impair vision (especially color vision) in the involved eye.
Optokinetic nystagmus consists of eye movements elicited by sequential fixation on a series of targets passing in front of a patient’s eyes, such as telephone poles seen from a moving train. For clinical testing, a revolving drum with vertical stripes or a vertically striped strip of cloth is moved across the visual field to generate these movements. Testing produces a slow following phase in the direction of the target’s movement, followed by a rapid return jerk in the opposite direction. The slow (pursuit) phase tests parieto-occipital and the rapid return (saccadic) movement tests frontal lobe function in the hemisphere toward which the stimulus is moved. The presence of an optokinetic response reflects the ability to perceive movement or contour and is sometimes useful for documenting visual perception in newborns or in psychogenic blindness. Visual acuity required to produce the optokinetic response is minimal, however (20/400, or finger counting at 3 to 5 ft). Unilateral impairment of the optokinetic response may be found when targets are moved toward the side of a parietal lobe lesion.
The eyelids (palpebrae) should be examined with the patient’s eyes open. The distance between the upper and lower lids (interpalpebral fissure) is usually approximately 10 mm and equal in both eyes, though physiologic asymmetries do occur. The position of the inferior margin of the upper lid relative to the superior border of the iris should be noted in order to detect drooping (ptosis) or abnormal elevation of the eyelid (lid retraction). The upper lid normally covers 1 to 2 mm of the iris.
Unilateral ptosis is seen with paralysis of the levator palpebrae muscle itself, lesions of the oculomotor (III) nerve or its superior branch, and Horner syndrome. In the last condition, ptosis is customarily associated with miosis and may be momentarily overcome by effortful eye opening.
Bilateral ptosis suggests a disorder affecting the oculomotor (III) nerve nucleus, neuromuscular junction (eg, myasthenia gravis), or muscle (eg, myotonic, ocular, or oculopharyngeal dystrophy).
Lid retraction (abnormal elevation of the upper lid) is seen in hyperthyroidism and in Parinaud syndrome caused by tumors in the pineal region (see later).
Abnormal protrusion of the eye from the orbit (exophthalmos or proptosis) is best detected by standing behind the seated patient and looking down at the eyes from above. Causes include hyperthyroidism (Graves disease, Figure 7-11), orbital tumor or pseudotumor, and carotid artery-cavernous sinus fistula. A bruit may be audible on auscultation over the proptotic eye in patients with carotid artery-cavernous sinus fistula or other vascular anomalies.
Graves ophthalmopathy in a 41-year-old woman. Note the protrusion of the right globe.
Ocular palsies and gaze palsies are detected by having the patient gaze in each of the six cardinal positions (see Figure 7-5). If voluntary eye movement is impaired or the patient is unable to cooperate with the examination (eg, is stuporous or comatose), reflex eye movements can be induced by doll’s head (oculocephalic) or cold-water caloric (oculovestibular) testing (see Chapter 3, Coma). If limitations in eye movement are observed, the muscles involved are noted, and the nature of the abnormality is determined according to the following scheme.
Weakness of one or more eye muscles results from nuclear or infranuclear (nerve, neuromuscular junction, or muscle) lesions. An ocular palsy cannot be overcome by caloric stimulation of reflex eye movement. Nerve lesions produce distinctive patterns of ocular muscle involvement.
Oculomotor (III) nerve palsy—A complete lesion of the oculomotor nerve produces closure of the affected eye because of impaired levator function. Passively elevating the paralyzed lid (Figure 7-12) shows the involved eye to be laterally deviated because of the unopposed action of the lateral rectus muscle, which is not innervated by the oculomotor nerve. Diplopia is present in all directions of gaze except for lateral gaze toward the side of involvement. Pupil function may be normal (pupillary sparing) or impaired (as illustrated).
Trochlear (IV) nerve palsy—With trochlear nerve lesions, which paralyze the superior oblique muscle, the involved eye is elevated during primary (forward) gaze; the extent of elevation increases during adduction and decreases during abduction. Elevation is greatest when the head is tilted toward the side of the involved eye and abolished by tilt in the opposite direction (Bielschowsky head-tilt test; Figure 7-13). Diplopia is most pronounced when the patient looks downward with the affected eye adducted (as in looking at the end of one’s nose). Spontaneous head tilting, intended to decrease or correct the diplopia, is present in approximately one-half of patients with unilateral palsies and in a greater number with bilateral palsies.
Abducens (VI) nerve palsy—An abducens nerve lesion causes paralysis of the lateral rectus muscle, resulting in adduction of the involved eye at rest (due to the uninvolved oculomotor nerve) and failure of attempted abduction (Figure 7-14). Diplopia occurs on lateral gaze to the side of the affected eye.
Clinical findings with oculomotor (III) nerve lesion. With the ptotic lid passively elevated, the affected (right) eye is abducted; it cannot adduct. On attempted downgaze, the unaffected superior oblique muscle, which is innervated by the trochlear (IV) nerve, will cause the eye to turn inward.
Clinical findings with trochlear (IV) nerve lesion. The affected (right) eye is elevated on forward gaze (A). The extent of elevation is increased with adduction (B) and decreased with abduction (C). Elevation increases with head tilting to the affected side (D) and decreases with head tilting in the opposite direction (E).
Clinical findings with abducens (VI) nerve lesion. The affected (right) eye is adducted at rest (A) and cannot be abducted (B).
Gaze palsy is the diminished ability of a pair of yoked muscles (muscles that operate in concert to move the two eyes in a given direction) to move the eyes in voluntary gaze; it is caused by supranuclear lesions in the brainstem or cerebral hemisphere. Gaze palsy, unlike ocular palsies, affects both eyes and usually can be overcome by caloric stimulation. Its pathophysiology and causes are discussed more fully in the section that follows on binocular disorders of eye movement. Mild impairment of upgaze is not uncommon in normal elderly subjects.
C. Internuclear Ophthalmoplegia
Internuclear ophthalmoplegia (INO) results from a lesion of the medial longitudinal fasciculus, an ascending pathway in the brainstem that projects from the abducens (VI) to the contralateral oculomotor (III) nerve nucleus (see Figure 7-6). As a consequence of INO, the actions of the abducens (VI) and oculomotor (III) nerves during voluntary gaze or caloric-induced movement are uncoupled. Excursion of the abducting eye is full, but adduction of the contralateral eye is impaired (Figure 7-15). INO cannot be overcome by caloric stimulation, but can be distinguished from oculomotor (III) nerve palsy by noting preserved adduction with convergence. It is usually caused by multiple sclerosis or brainstem stroke.
Eye movements in internuclear ophthalmoplegia (INO) resulting from a bilateral lesion of the medial longitudinal fasciculus.
D. One-and-a-Half Syndrome
A pontine lesion affecting both the medial longitudinal fasciculus and the ipsilateral paramedian pontine reticular formation (lateral gaze center) produces a syndrome that combines internuclear ophthalmoplegia with an inability to gaze toward the side of the lesion (Figure 7-16). The ipsilateral eye is immobile in the horizontal plane, and movement of the contralateral eye is restricted to abduction, which may be associated with nystagmus. The causes include pontine infarct, multiple sclerosis, and pontine hemorrhage.
One-and-a-half syndrome. This results from a pontine lesion (blue area) involving the paramedian pontine reticular formation (lateral gaze center), medial longitudinal fasciculus, and sometimes also the abducens (VI) nucleus, and affecting the neuronal pathways indicated by dotted lines. Attempted gaze away from the lesion (A) activates the uninvolved right lateral gaze center and abducens (VI) nucleus; the right lateral rectus muscle contracts, and the right eye abducts normally. Involvement of the medial longitudinal fasciculus interrupts the pathway to the left oculomotor (III) nucleus, and the left eye fails to adduct. On attempted gaze toward the lesion (B), the left lateral gaze center cannot be activated, and the eyes do not move. There is a complete (bilateral) gaze palsy in one direction (toward the lesion) and one-half (unilateral) gaze palsy in the other direction (away from the lesion), accounting for the name of the syndrome.
When the patient complains of double vision (diplopia), eye movements should be tested to determine its anatomic basis. The patient is asked to fix vision on an object, such as a flashlight, in each of the six cardinal positions of gaze (see Figure 7-5). With normal conjugate gaze, light from the flashlight falls at the same spot on both corneas; a lack of such congruency confirms that gaze is disconjugate. When the patient notes diplopia in a given direction of gaze, each eye should be covered in turn and the patient asked to report which of the two images disappears. The image displaced farther in the direction of gaze is always referable to the weak eye, because that image will not fall on the fovea. A variation of this procedure is the red glass test, in which one eye is covered with translucent red glass, plastic, or cellophane; this allows the eye responsible for each image to be identified.
Nystagmus is rhythmic oscillation of the eyes. Pendular nystagmus, which usually has its onset in infancy, occurs with equal velocity in both directions. Jerk nystagmus is characterized by a slow phase of movement in one direction, followed by a fast phase in the opposite direction; the direction of jerk nystagmus is specified by stating the direction of the fast phase (eg, leftward-beating nystagmus). Jerk nystagmus usually increases in amplitude with gaze in the direction of the fast phase (Alexander law).
Nystagmus can occur at the extremes of voluntary gaze in normal subjects and is also a normal component of both the optokinetic response and the response to caloric stimulation of reflex eye movements. In other settings, however, it may be due to anticonvulsant or sedative drugs or disease in the peripheral vestibular apparatus, central vestibular pathways, or cerebellum.
To detect nystagmus, the eyes should be observed in the primary position and in each of the cardinal positions of gaze (see Figure 7-5). Nystagmus is described in terms of the position of gaze in which it occurs, its direction and amplitude, precipitating factors such as changes in head position, and associated symptoms, such as vertigo.
Many forms of nystagmus and related ocular oscillations have been described, but two syndromes of acquired pathologic jerk nystagmus are by far the most common.
Gaze-evoked nystagmus occurs when the patient attempts to gaze in one or more directions away from the primary position. The fast phase of nystagmus is in the direction of gaze. Nystagmus evoked by gaze in a single direction is a common sign of early or mild residual ocular palsy. Multidirectional gaze-evoked nystagmus is most often an effect of anticonvulsant or sedative drugs, but can also result from cerebellar or central vestibular dysfunction.
Nystagmus caused by a lesion of the peripheral vestibular apparatus is characteristically unidirectional, horizontal, or both horizontal and rotatory oscillations, as is associated with severe vertigo. Its amplitude increases with gaze toward the fast phase. In contrast, central vestibular nystagmus may be bidirectional and purely horizontal, vertical, or rotatory, and the accompanying vertigo is typically mild. Positional nystagmus, elicited by changes in head position, can occur with either peripheral or central vestibular lesions. The most helpful distinguishing features are the presence of hearing loss or tinnitus with peripheral lesions and of corticospinal tract or additional cranial nerve abnormalities with central lesions.