Chapter 3
Neuro-ophthalmologic Examination: General Considerations and Special Techniques
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  Ocular Motility
  Range and Character of Eye Movements

  Fixation and Ocular Stabilization
  Conjugate Gaze: Versions

  Special Techniques

  Examination of Infants
  Optokinetic Nystagmus
  Bell's Phenomenon and Spasticity of

  Conjugate Gaze
  Neuroanatomy and Physiology
  Position and Movements
  Lid Retraction
  Lid Nystagmus
  Ocular Sensation and Pain
  Functional Anatomy

  Peripheral Trigeminal Afferents
  Trigeminal Sensory Nuclei
  Trigeminal Ascending Pathways

  Clinical Evaluation of Trigeminal Function
  Abnormal Corneal Reflexes
  Pain in and about the Eye
  Defective Tearing
  Neuralgia and Atypical Facial Pain

The Comatose Patient

Since neuro-ophthalmologic examination makes use of ophthalmologic means and devices but aims at a neurologic diagnosis, it occupies a kind of intermediate position and suffers neglect from both sides. Many neurologists are not familiar enough with the detailed technique of the ophthalmologic methods; ophthalmologists are often not concerned with the details of neurologic localization.

Alfred Kestenbaum, 1946

Clinical Methods of Neuro-ophthalmologic Examination

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In the examination of ocular motility, it is helpful for the physician to follow an orderly protocol that logically subdivides the different types of eye movement. There is sufficient clinical and experimental evidence to substantiate the existence of several subsystems for the control of eye movement and position. The pragmatic clinical analysis of defective eye movements must take into account these newer concepts of ocular motor mechanisms. A complete discussion of the anatomy and physiology of eye movements is found in Chapter 10.


It is through familiarity with the normal that we may distinguish the abnormal. Therefore, this discussion begins with a brief description of typical and normal eye movement. As with the determination of visual function, observation of ocular motility begins as the patient enters the examination room and continues during history taking. The physician should note normal or abnormal spontaneous gaze and eye position. It is especially rewarding to observe the spontaneous eye movements of infants and young children, before the “threat” of actual physical examination.

Fixation and Ocular Stabilization

In the human, eye movements occur so that a focused image is projected onto the central fixational area of the retina, the fovea. Here visual function is greatest because of the concentration of receptor cells. A stimulus that falls on the peripheral retina provokes an eye movement that realigns the visual axis of the eye so that the fovea “acquires” the visual direction of that stimulus; that is, the eye “fixates” the stimulus that now becomes the object of regard. The eye movement that acquires the target is the “fixational reflex,” and the steady “lock on” of the fovea is “fixation.”

It is obvious that ocular fixation, in acquiring and holding a target, requires reasonably good visual acuity, although more peripheral parts of retina have some fixational capacity. Therefore, the afferent visual pathways from retina to cortex play a major role in fixation, but there must be a counterpart motor efferent that precisely guides the fixational eye movement to target and then maintains punctilious gaze. The ability of one or both eyes accurately and steadily to fixate a target (muscle light, finger, or pencil) is a prerequisite for evaluating other types of eye movement. For example, if one eye fixates poorly due to dense central scotoma, the cover-uncover or alternate-cover test has limited value.

Fixational movements may be voluntary (the quick eye movements as one looks about a room) or involuntary (when a bright light suddenly appears in the far peripheral field). The involuntary fixational reflex may alternately be called a “visually elicited eye movement”; that such eye movements may be provoked, is used as evidence of peripheral field function in infants (see below). In either case, when the object of regard is acquired by the fovea, fixation is steady, and the eye continues smoothly to track (a pursuit movement) a target that is slowly moved, much as a radar system acquires a target, locks on, and smoothly tracks.

The stability of fixation is quickly determined simply by having a patient (even a baby) gaze at a target (light, pencil, small cartoon character, or hand puppet). Fixation should be steady and unwavering. If the target is slowly moved from side to side, the eyes move smoothly to maintain fixation without “slippage” off the target. These ocular pursuit movements are discussed below. Fixation should be tested binocularly as well as with each eye separately.

Conjugate Gaze: Versions

The ability of the eyes to move symmetrically and synchronously in the same direction, horizontally or vertically, is termed “conjugate” (yoked together) gaze. These versional movements may be rapid (a saccade), as in the command to “look left,” or during the reflex to take up fixation (see above), or may be slow as in the smooth tracking (pursuit) of a slowly moving target. Saccadic and pursuit sub-systems are discussed in some detail in Volume 2, Chapters 9 through 11.

Conjugate gaze is tested by asking the patient to “look right … left.” The patient is then asked to “follow” (“let your eyes follow”) some target such as the examiner's hand-held light (Fig. 1). Command horizontal eye movements should be rapid and symmetric in the two eyes. Binocular excursions (both eyes open) are generally smaller than monocular (one eye covered), and the eyes move through approximately 45° to either side of the straight forward position (i.e., primary gaze). Abduction is difficult to sustain beyond 35° of eccentricity, and a physiologic end-gaze nystagmus is quite common (see Volume 2, Chapter 11). In the abducting eye, the temporal aspect of the corneal margin should almost approximate the outer angle (lateral canthus) of the lids, with little sclera visible. In elderly patients with lax facial tissues, the external lid angle may be displaced so that a minimal rim of sclera is still visible in the abducted position. The adducting eye is positioned such that 1 mm to 2 mm of the nasal aspect of the cornea may be buried in the folds of conjunctiva and caruncle at the inner canthal angle.

Fig. 1. Examination of ocular versions. Horizontal pursuit is toward the right.

Vertical conjugate gaze is somewhat more difficult to assess. Downward gaze should be at least 45°, but since the lower lid is indented by the cornea, there is no constant landmark. Upward gaze is even more difficult to assess. Chamberlain1 reported a progressive restriction in upward ocular versions with advancing age: 95 patients aged 5 to 34 years had 36° to 40° of elevation; 125 patients aged 65 to 94 years had 16° to 22° of elevation.

Conjugate versions may also be tested without the patient's active cooperation, by directing attention to a distant target (e.g., a wall-mounted light, or even while an acuity chart is being read), and passively rotating the patient's face to the right, left, up, and down.


Convergence is an associated, but disjugate, movement, in that the eyes move toward each other, rather than turning toward the same side (i.e., conjugate). It is usually accomplished by synchronous action of both medial recti muscles as in reading or other near-visual tasks, but convergence may be blended with a conjugate gaze, for example, fixating a near object directly in front of one eye. The neural mechanisms responsible for adduction during lateral conjugate gaze, and during convergence, are separate and may be dissociated in pathologic states, for example, in patients with internuclear ophthalmoplegia.

It is helpful to test convergence capability in the following neuro-ophthalmologic situations: (1) if pupillary light reactions are absent or sluggish, the pupils are observed during convergence (more precisely, during the near-effort reflex); (2) if there is lag of the adducting eye on lateral conjugate gaze suggesting an internuclear ophthalmoplegia; (3) any bilateral external ophthalmoplegia; and (4) in acquired exotropia, in which monocular ductions are full, suggesting convergence paralysis.

Convergence strength varies considerably and depends principally on the cooperation of the patient. A sure sign that the patient is indeed attempting to converge is simultaneous pupillary constriction. Of course, there are pathologic states that involve both convergence and pupillary constriction (e.g., Parinaud's dorsal midbrain syndrome). It is helpful if the patient's own finger is used as a convergence target. Thus, even in a blind patient, convergence may be examined using proprioceptive clues to the nearness of one's finger or hand. Reticence to attempt to gaze at one's finger, or histrionic avoidance, may signal a functional disorder or dissembling.


Examination of Infants

In order to determine the extent of conjugate eye movements in infants, it is often necessary to resort to special clinical techniques and manipulations. However, initial observation of spontaneous versions and fixation may suffice, and such observations should begin before the infant or young child is startled or anxious. Otherwise, visually elicited eye movements are provoked by objects that attract an infant's attention (see Volume 2, Chapter 2, Fig. 9) and therefore also provide a gross estimation of visual function. Similarly, a child turns head and eyes toward a sound (jingling keys). This is an acoustically elicited eye movement that does not require sight, however, and so no conclusions may be drawn regarding vision. If the child accurately fixates and follows any silent object, that is good evidence of reasonably intact vision.

If the examiner holds a neonate upright, face to face, and turns, the neonate's eyes undergo a tonic deviation in the direction of the turn (Fig. 2). This tonic, conjugate eye deviation is a result of labyrinthine stimulation and does not depend on vision. The fast phase (jerk) of such rotation induced nystagmus may be absent in the premature neonate, but it is usually present before 1 week of age. Rotational maneuvers are helpful in determining the state of brain stem systems for conjugate horizontal gaze. Failure to elicit eye movement on rotational testing infers a major pontine or extraocular muscle abnormality. Brisk rotation of the head, vertically and horizontally, on the long axis of the body (“doll's head” phenomenon), produces tonic contralateral horizontal deviation of the eyes in the neonate.

Fig. 2. Rotational testing for eye movement function in infants. As the infant is spun toward its left (toward the examiner's right), the eyes will tonically deviate in the direction of the movement, with the jerk phase of nystagmus toward the opposite side. The open arrow indicates the induced axis of rotation of the infant's head. Note the influence of head rotation on the right and left semicircular canals (SCC).

Optokinetic nystagmus (OKN; see below) may be used to determine ocular motility, but induced OKN movements are less extensive than with rotational stimulation. Disparity between vertical and horizontal response or between optokinetic and rotational responses may indicate a disorder of supranculear gaze mechanisms, such as in congenital ocular motor apraxia or congenital nystagmus (see Volume 2, Chapter 13).

Optokinetic Nystagmus

If a series of vertical bars or other such patterned contours is passed before the eyes (Fig. 3), a visually induced nystagmus occurs. This nystagmus was apparently first adequately described by Helmholtz, who observed the eyes of passengers gazing out of train windows at the passing countryside. This phenomenon is easily noted in riders of subway trains, buses, and so forth. There is a slow following phase toward the side of target movement (or at the passing scene) and a rapid jerk return in the opposite direction. The character of OKN is partially dependent on the speed of target movement, the pattern density, and the subject's visual function and state of attentiveness. Because the slow phase is initiated by vision, OKN may be used as a rough parameter of visual function. As noted by Linksz,2 OKN is more closely related to movement perception or contour recognition than to visual acuity. Actually, suppression of OKN response by interposition of a fixation target of variable size is best correlated with “acuity.” It should be recognized that OKN represents an innate and highly complex ocular motor reflex evoked by perception of moving contours, which is only distantly related to visual acuity. In clinical practice, only a rough estimate of visual “acuity” is obtained with the usual optokinetic devices. Examples of the minimum visual requirement with a stimulus at 2 to 4 feet (see Fig. 3) are presented below:

Fig. 3. Optokinetic nystagmus. The movement of a striped drum (A) or squares on a cloth (B) evokes a nystagmus that beats opposite the direction of target movement.

  1. Striped drum: finger count 3 to 5 feet.
  2. Squares on flag: finger count 3 to 5 feet.
  3. Tailor's tape: 20/400 to 3/200.

OKN is an especially useful technique in infants as a test of gross visual function, and it should be demonstrable to some degree even in newborns. It is positive evidence of sight in malingerers and hysteric patients, and it is similarly productive in evaluating uncooperative, semiobtunded, or dysphasic patients. Central vision need not be good to have intact OKN response if gross pattern stimuli are used (see Fig. 3). It is evident that visual impulses trigger a cerebral mechanism that more or less regulates the rhythmicity of the nystagmus. OKN is affected by nonvisual factors and may even be observed in hypnotic states, although the character of the OKN is not strictly parallel to that induced by actual visual stimuli. An optokinetic after-nystagmus may be demonstrated on cessation of target rotation, especially if fixation is inhibited by dark environment or lid closure. Further evidence of nonlinearity of visual input and optokinetic response was demonstrated in the rabbit by Collewijn,3 but it is also true in the human patient who meets the criteria for conducting the demonstration; if a gross OKN stimulus is presented monocularly before a seeing but immobile eye, optokinetic response is observed in the occluded or blind, but mobile, fellow eye.

Optokinetic response as a useful clinical tool was first popularized by Kestenbaum,4 and later by Cogan and Smith,5 and others. Cerebral lesions deep in the parietal lobe cause homonymous hemianopias and also interrupt the descending occipitomesencephalic system for slow (pursuit) eye movements.

The occipital optomotor fibers descend in the internal sagittal stratum and are medial to the geniculocalcarine radiations in their posterior course through the parietal lobe. Lesions here consistently produce a homonymous hemianopia (contralateral) and a defective OKN when targets are moved toward the side of the lesion. The defective OKN (a “positive OKN sign”) is not due to targets coming out of the hemianopia, as originally thought by Barany, because strictly occipital or temporal lobe lesions producing profound hemianopias are not associated with a positive (i.e., asymmetric) OKN response. Therefore, in the presence of a homonymous hemianopia, a defective OKN response indicates deep parietal involvement. This sign is considerably more helpful when the nondominant (right) parietal lobe is involved (left hemianopia). When the dominant (usually left) parietal lobe is involved, there are consistently other localizing signs and symptoms, such as motor and sensory dysphasias.

OKN may be helpful in elucidating volitional (saccadic) gaze palsies, with intact pursuit movement. For example, a patient with a right frontal lesion may show an inability to make command eye movements to the left, but slow-moving targets will produce smooth pursuit toward the left. Because pursuit to the left is intact and saccades to the right are normal, with targets rotated toward the left a normal OKN response is seen. However, with targets toward the right, the fast phase leftward cannot be generated, and a tonic deviation toward the right will result, as though the eyes are drawn in that direction by the rotating drum or tape.

OKN is a useful mechanism to amplify muscle pareses by inducing an asymmetric response of yoke muscles, best observed in the fast (saccadic) phase. For example, a subtle weakness of adduction (as seen in internuclear ophthalmoplegia) may be uncovered by observing a grossly dissociated OKN response when the paretic muscle is challenged to make a saccade (i.e., with targets rotated opposite the field of action of the paretic muscle). Thus, the adduction lag of the left eye with left internuclear ophthalmoplegia is enhanced by target rotation toward the left that induces fast phase to the (defective) right. Similarly, a command saccade from left to right also enhances the adduction lag; that is, a grossly slowed rightward saccade of the left eye is observed.6 Despite the complexities of the neurophysiologic basis for OKN, it is a simple and practical clinical maneuver with multiple applications in elucidating defects in the ocular motor system (see Volume 2, Chapter 10).


Double vision is a disturbing symptom that most patients cannot ignore, but many are unable to describe adequately. Diplopia may be intermittent at first, as the patient's fusional mechanism is not overtaxed, or it may first be noticed only for distant vision (suggesting lateral rectus paresis) or principally during near-vision tasks (suggesting medial rectus or superior oblique paresis). The issue may be clarified by the following questions:

  1. When and how was the double vision first noticed?
  2. Were there other symptoms when the double vision began: light-headedness, dizziness, or spinning; weakness or tingling in face, arm, or leg; difficulty with speech or swallowing (or other signs and symptoms of vertebrobasilar ischemic episode); facial or ocular pain?
  3. Did one or both lids droop? Before or since?
  4. Are the images side by side, one above the other, or a combination?
  5. Is one image tilted (suggests superior oblique palsy)?
  6. Is it worse in the distance or while reading?
  7. Is the double vision the same throughout the day?
  8. Since first noticed, has it gotten worse, better, or stayed about the same?
  9. Can the head and face be turned or tilted to avoid the double vision?
  10. Is there a medical history of trauma, diabetes, hypertension, or dysthyroidism?

General inspection of the patient should include observation for spontaneous head tilt or face turn. While taking the history, the physician notes the position of the lids and looks for partial or total ptosis (myasthenia, third nerve palsy, Horner's syndrome) or unilateral or bilateral lid retraction (dysthyroidism). Signs of local orbital disease should be sought: proptosis, lid edema, and inflamed or hypervascular conjunctiva (see Volume 2, Chapters 12 and 14).

Almost all diplopia occurs as the result of an acquired paresis or palsy of one or more extraocular muscles. However, a child who insidiously develops a nonparalytic comitant squint may rarely complain of diplopia. In addition, in instances of fusional disturbances, such as convergence insufficiency, double vision may be a major symptom (see Volume 2, Chapter 13). These conditions are defined by appropriate examination techniques that demonstrate their nonparalytic characteristics; that is, monocular ductions are full, and angle of deviation remains the same regardless of which eye is made to fixate a target. In other words, in nonparalytic strabismus, the angle of muscle imbalance (squint) is essentially constant, and each eye has a full range of motion if tested separately.

Monocular diplopia (or perhaps more accurately, a “ghost image”) is an uncommon complaint and is usually the result of opacities of the cornea or lens, a high degree of astigmatism, or a partially dislocated lens. The use of a pinhole should solve this diagnostic dilemma (see Volume 2, Chapter 1). Kommerell7 described monocular diplopia caused by pressure of the upper lid that deforms the regular curvature of the cornea. The diagnosis is confirmed by an abnormal retinoscopic reflex, the “Venetian blind phenomenon.”

Bender8 reported instances of polyopia and monocular diplopia of cerebral origin (cerebral polyopia) accompanied by major field defects and other signs of parietal dysfunction, including: spatial disorientation, fluctuating extinction of images, extinction of cutaneous sensation, and disturbances of ocular fixation, which he attributed to occipital lobe disease (see Volume 2, Chapter 7).

In general, the complaint of diplopia indicates an acquired cranial nerve or extraocular muscle disorder that must be confirmed and investigated in an orderly, step-by-step analysis of ocular motility. It is beyond the scope of this work to present a detailed discussion of the anatomy and physiology of the extraocular muscles. However, a brief outline of basic ocular motility follows, primarily for the convenience of readers not formally trained in ophthalmology.

Each eye is maneuvered by six extraocular muscles, each of which has a partner in the contralateral orbit for coordinated simultaneous movement of the fellow eye. Muscles working in pairs for conjugate gaze are called “yoke” muscles. If we consider six cardinal positions of gaze, there are six pairs of yoke muscles that act as the prime movers in those six positions of gaze. Thus, on gaze rightward, the right lateral rectus and left medial rectus are yoke muscles. Each extraocular muscle has an ipsilateral antagonist that must relax if the globe is to move. Therefore, as the lateral rectus contracts to abduct the globe, its antagonist, the medial rectus, is simultaneously inhibited.

The six muscles of each eye may functionally be grouped in three pairs: the two horizontal recti (lateral and medial); the two vertical recti (superior and inferior); and the two obliques (superior and inferior). Each of these pairs represents an agonist-antagonist combination.

Numerous procedures have been devised to assess the function of the extraocular muscles, but if weakness is recent and moderate to marked, a simple test of versions (conjugate gaze) will usually suffice. It is also helpful to note the relative positions of the binocular corneal light reflections, as well as the gross positions of the globes. Mild limitations of movement often can more readily be detected during observation of binocular movements, as the eyes are turned into the “field of action” of the paretic muscle.

According to Hering's law, yoke muscles receive equal and simultaneous innervation. This phenomenon provides a sensitive mechanism for the detection of subtle muscle pareses. For example, the right lateral rectus and left medial rectus are yoke muscles for right horizontal gaze. If the right lateral rectus is paretic and fusion is consequently broken, the patient must elect to fixate an object with one eye or the other. If the nonparetic left eye fixates, there is an inward deviation (esotropia) of the right eye resulting from paresis of right lateral rectus, as well as relatively unopposed contraction of the medial rectus. This is called the primary deviation (Fig. 4). If, however, the paretic eye fixates, or is forced to fixate (by occluding the intact eye), then additional innervation is required in an attempt to activate the paretic lateral rectus. This excessive innervation determined by the effort of the paretic eye to fixate, according to Hering's law, will also be equally transmitted to the intact left medial rectus, which now “overacts” and excessively adducts the sound eye. This overaction of the nonparetic eye, when the paretic eye is forced to fixate, is termed secondary deviation and is greater than primary deviation.

Fig. 4. Alternate cover test used, for example, with palsy of the right lateral rectus muscle (RLR). A. With a cover over the right eye, the left (nonparetic) eye fixates and the right eye is moderately deviated inward (primary deviation). B. If the paretic right eye is forced to fixate, increased innervation (+ + + ) is delivered to both the paretic RLR and its normal yoke muscle, the left medial rectus (LMR). Subsequent overaction of the LMR markedly deviates the nonparetic eye (secondary deviation).

The difference in size of primary and secondary deviation is evident when the alternate cover test is used. This is an excellent objective and reproducible method to analyze paretic ocular muscles, but it requires sufficient visual function for adequate central fixation with each eye. The previous discussion (and see Fig. 4) showed that the occluded eye deviates; for example, the right eye with a lateral rectus paresis deviates inward behind the occluder. If the occluder is now quickly switched to the other eye, the right eye will make an outward movement to “take up fixation,” and this movement is easily observed. Rapid alternation of occluder from one eye to the other (approximately 1 to 2 seconds) provokes an easily discernible and reproducible pattern of fixational eye movements. The alternate cover test may be performed in the six cardinal positions of gaze to discover (1) the field of gaze in which deviation is greatest and (2) in that field of gaze, which eye fixation produces the greater deviation. The difference in the angle of deviation from one field of gaze to the other, and with each eye fixating, may be roughly estimated or accurately measured by prism neutralization.

Diplopia “fields” may be performed by placing a red glass over one eye (by convention, the right) and having the patient indicate the field of gaze of greatest subjective separation of images. This test demonstrates the relative position of the two eyes with respect to one another. With an esotropic deviation (inward turn) the images are uncrossed, that is, the red (right eye) image is toward the right; with an exotropic deviation, the images are crossed, the red image toward the left. The more peripheral-appearing image belongs to the paretic eye. It is helpful if the patient holds up two fingers to demonstrate the relative position of the two images, which should change as the eyes are moved into different gaze directions (Fig. 5). The Maddox rod is a series of parallel cylindrical bars that transform a point source of light into a line perpendicular to the cylinder axes (see Fig. 5). If a red Maddox rod is used, the right eye sees a straight vertical or horizontal red line, which may be compared with the position of a white point source of light seen with the left eye. Torsional deviations, such as those that occur with superior oblique palsies, may be uncovered by subjective appearance of tilting of the Maddox rod image. Special techniques for testing function of the superior oblique are discussed in the section related to fourth nerve palsy (see Volume 2, Chapter 12).

Fig. 5. Subjective diplopia examination using a Maddox rod. With the cylinders held horizontally (A) or vertically (B), the patient indicates position of images. C. Demonstration of the effect of the Maddox rod on the point light source, that is, formation of a line perpendicular to the axes of the series of cylinders.

Every patient with diplopia, the cause of which is not obvious, and that is not accompanied by pain or involvement of the pupil, should raise the possibility of myasthenia, for which an intravenous edrophonium (Tensilon) test should be considered. Myasthenia gravis can affect the extraocular muscles singly or in any combination, with or without ptosis, and it is most assuredly a commonly missed diagnosis unless the physician keeps the disease in mind and a syringe at hand (see Volume 2, Chapter 12).

The local orbital inflammatory reaction that consistently accompanies dysthyroid states is a common cause of extraocular muscle restriction. The situation of a middle-aged woman with isolated vertical diplopia represents a monotonous clinical picture with which neurologists and ophthalmologists alike should be thoroughly familiar. If, for good measure, there is unilateral or bilateral lid retraction, the diagnosis is made regardless of the absence of other clinical or chemical signs of dysthyroidism (see Volume 2, Chapters 12 and 14).

In order to establish the presence of a restrictive local orbital myopathy, the forced duction test is used. This test determines the presence of mechanical resistance by actually taking hold of the globe and attempting to move it in the direction that the patient cannot (Fig. 6; see Volume 2, Chapter 14). It should be pointed out that in any long-standing ocular deviation, whether due to sixth nerve palsy, ocular myasthenia, or congenital esotropia, there may be secondary changes in muscles with contractures and therefore a “positive forced duction test.” The conclusions of Kommerell and Oliver9 are apparently valid: any paresis of an extraocular muscle ultimately results in a contracture of the ipsilateral antagonist; and secondary changes in the nonparetic eye (contracture of yoke muscle) occur only if the paretic eye fixates continuously.

Fig. 6. Forced duction test. A. Inability of the patient to elevate the right eye on upward gaze. B. Using cocaine 10%, the insertion of the right inferior rectus muscle is anesthetized. C. The insertion of the inferior rectus is grasped with toothed forceps (Elschnig), and, with the patient looking upward, an attempt is made manually to rotate the right globe upward. D. For comparison, the left globe is manually rotated upward following instillation of cocaine.

The characteristics of paralytic strabismus, that is, differences in primary and secondary deviation and variation of squint angle with different fields of gaze, are most marked when the paresis is recent. These differences become less marked with time, and the strabismus becomes more symmetric, that is, less incomitant. This phenomenon is the so-called spread of comitance. A sequence of events takes place such that comitance emerges; for example, if the right lateral rectus muscle is paretic, the following occur in some degree: (1) overaction (secondary deviation) of the contralateral yoke, the left medial rectus; (2) contracture of the ipsilateral antagonist, the right medial rectus, such that the angle of the inward turn increases; (3) in the presence of hypoactivity of the antagonist, the right medial rectus, its contralateral yoke muscle, the left lateral rectus, will become apparently paretic, especially if the paretic eye is used for fixation (inhibitional palsy of Chavasse); and (4) therefore, the esotropic deviation increases in the field of gaze of the left lateral rectus, as well as in the field of gaze of the originally paretic right lateral rectus.

Bell's Phenomenon and Spasticity of Conjugate Gaze

In 1823, Sir Charles Bell reported on the oculogyric phenomenon that accompanies forceful closure of the eyelids, which Bell first noted as an upward deviation of the globe during attempted eyelid closure in the presence of the peripheral facial palsy that now bears his name.10 Bell's phenomenon is an associated movement of eyes and orbicularis oculi, such that the eyes typically roll upward and outward when efforts are made to close the eyelids against resistance (Fig. 7). The exact neural mechanism for this integrated movement is unknown, but it involves brain stem pathways between the seventh nerve nucleus in the pons and the third nerve nuclear complex in the rostral midbrain. In patients who cannot volitionally elevate the eyes, intact Bell's phenomenon (like doll's head deviation upward) indicates that brain stem pathways, the nuclear cell complex for upward gaze, the associated motor neurons, and the extraocular muscles related to eye elevation are functioning, and that the upward-gaze palsy is due to a supranuclear defect.

Fig. 7. Bell's phenomenon. Forced lid closure against resistance produces upward and outward deviation of the eye.

Cogan11 studied the occurrence of abnormal Bell's phenomenon and found that in a series of 156 persons with no known neurologic disease, 132 showed upward or upward and outward deviation of the eyes, that is, the anticipated ocular deviation with forced lid closure. In that presumed normal control group, no deviation from the primary position was observed in 11, convergence occurred in 5, downward deviation was noted in 3, wandering movements occurred in 2, and conjugate lateral deviation was seen in 3. A second group of patients in Cogan's study was composed of 78 patients with unilateral cerebral or infratentorial lesions, with reasonably definite localizing signs. Of the 54 patients with presumed unilateral cerebral disease, 34 showed a lateral conjugate deviation of the eyes to the side opposite the lesion, 5 to the same side, and 15 showed no deviation, with forced lid closure. Twenty-four patients with unilateral lesions of the cerebellum, brain stem, or labyrinth demonstrated no consistent deviation. Eye movements related to simple blinking are rapid, and the eyes actually deviate and return to their original position even before the blink is completed.12

The pathologic reflex of conjugate deviation of the eyes to the side opposite a cerebral lesion, was called “spasticity of the conjugate oculomotor mechanism” by Cogan. The spastic deviation is not dependent on conjugate-gaze paralysis and, in fact, occurs toward the side opposite that which would be anticipated with a cerebral gaze palsy. Smith and colleagues13 emphasized that spasticity of conjugate gaze has lateralizing rather than localizing significance; this phenomenon has its highest correlation with temporo-parietal lesions, is less frequent with occipital disorders, and is not seen with frontal lobe disease. There is apparently no consistent association of spasticity of conjugate gaze with homonymous hemianopia, long-tract signs, or abnormal optokinetic response. As an isolated finding, spasticity of conjugate gaze should bear no diagnostic weight.

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Careful observations of the resting position of the eyelids, rate and extent of blinking, synkinetic movement with the eyes and facial muscles, and spontaneous movement abnormalities all provide useful information for neuro-ophthalmologic diagnosis. “Lid watching” is a lost art, and errors of omission in the physical examination have cost more than one dysthyroid patient the price of inappropriate diagnostic procedures.


The neural control of eyelid function is well reviewed by Schmidtke and Buttner-Ennever.14 The eyelid is elevated and its resting position is maintained primarily by the levator palpebrae superioris. This muscle is innervated by the superior division of the oculomotor nerve, with motoneurons that originate in a midline dorsocaudal nucleus of the oculomotor nuclear complex in the midbrain. Because of its dorsal position, the levator nucleus may be spared or preferentially involved exclusive of other oculomotor nerve functions. Damage to the levator nucleus results in bilateral ptosis.

Pre-motor neurons that influence lid movements are located in the brain stem reticular formation and receive input from multiple suprasegmental sources that execute bilateral lid widening (via oculomotor nerve branches to the levator palpebrae superioris) or aperture narrowing (orbicularis oculi). There is a direct relationship of tonic activity of the levators and level of alertness; the lids widen with attentiveness and arousal, they lower involuntarily with increasing fatigue, and eventually, it is impossible to keep them from closing. During sleep, levator activity ceases completely.

Blink reflexes occur in response to touch or other corneal stimulation and to sudden bright illumination (perhaps via a direct pre-tectal-facial projection that bypasses the occipital cortex), or they are induced by sound or general startle reflex.15 During a simple blink, the levator palpebrae is abruptly inhibited and the palpebral portion of the orbicularis oculi contracts; thus, there is a coordinated synkinesis involving the oculomotor nerve (levator) and facial nerve (orbicularis) during both spontaneous and voluntary blinking.

Motor cortex, extrapyramidal system, and rostral midbrain structures are involved with levator palpebrae control, and coordination with vertical gaze is integrated by the rostral interstitial nucleus of the medial longitudinal fasciculus. For example, on downward gaze, the levators are progressively inhibited, but the orbicularis oculi does not contract.

The ventral periaqueductal gray is assumed to control generation of tonic levator neuronal activity, and caudal supraocular neurons mediate converging inhibitory inputs to the levator motor neurons. Cerebral localization for voluntary lid widening, or reflex elevation in coordination with eye and head movements, is not precisely understood. Experimental cortical lesions of the frontal motor area, angular gyrus, and temporal lobe can all produce ptosis, and electrode stimulation of the frontal, temporal, and occipital cortices results in lid opening. Unilateral or bilateral ptosis, cerebral ptosis, may occur from unilateral temporal and temporo-parietal or bilateral frontal lobe disease.16,17 Lesions in frontal, temporal, and occipital areas have been associated with ptosis or dysfunction of voluntary lid control.14 Extrapyramidal system disorders such as parkinsonism and progressive supranuclear palsy are associated with blepharospasm and supranuclear apraxias of lid opening; these are discussed in Volume 2, Chapter 8.

In the upper lid, Müller's muscle consists of a thin sheet of smooth muscle fibers that connects the upper tarsus to the undersurface of the levator. The superior tarsal muscle is innervated by the cervical sympathetics, damage to which results in ptosis as part of Horner's syndrome. A small inferior tarsal muscle also regulates the height of the lower lid. Sympathetic tone appears to modulate static lid position.

The two upper lids are “yoked,” and their synkinetic movements with the eyes in vertical gaze positions are synchronous and symmetric,18 but with horizontal gaze one eye may widen more than the other.19 That Hering's law of equivalent innervation may be applicable to the two levators, even in the primary gaze position, is debatable.20 In some patients with partial unilateral ptosis, such as in myasthenia, retraction of the contralateral upper lid may be attributable to increased innervation in an attempt to widen the abnormally narrowed palpebral fissure (Fig. 8). If the ptotic side is occluded, the opposite “retracted” lid assumes a normal position.

Fig. 8. Demonstration of the law of equivalent innervation (Hering's law) applicable to lid levators. A. A patient with myasthenia attempts to overcome right ptosis. Increased -levator innervation results in contralateral lid retraction (arrow). Note also elevated brows resulting from frontalis effort. B. After administration of edrophonium chloride (Tensilon), right ptosis is relieved and the left fissure narrows. Note frontalis relaxation with descent of the brows.

Compensatory unilateral lid retraction is uncommon, and factors other than Hering's law may play an important role. For example, if the eye with ptosis is also preferred for visual fixation, as opposed to fixation preference for the nonptotic eye, compensatory retraction is more likely.21 Other examples of compensatory lid retraction include deficits of supraduction of a downward deviated eye, such as in Graves' disease, that disproportionately raise the contralateral lid.22


In neuro-ophthalmologic context, the eyelid examination should include the following observations:

  1. Position at rest with eyes straight ahead: the palpebral fissures should be equal (from lower to upper lid margin measures 9 mm to 12 mm); the prevalence of physiologic fissure asymmetry (1 mm or more) is reckoned at about 6%;19 the upper lids drape over the corneal limbus covering the superior 1 mm to 2 mm of cornea; the lower lid edge touches at or just above the lower corneal limbus (Fig. 9). (Lid position obviously varies with individual physiognomy, laxity of facial tissues, and the position of the globe with respect to the orbital rim).
  2. The shape of the lid may be altered by local inflammations of the lid margins or conjunctiva, or after trauma, including surgical manipulations; on occasion, the configuration of the lid margin takes on special significance, such as the S-shaped lid in neurofibromatosis (Fig. 10)
  3. Synkinetic coordination with eye movements; in conjugate lateral gaze (see Fig. 9), Lam and associates19 found that palpebral fissure asymmetry increased by a tendency of the adducting eye to widen slightly; levator tone increases on upward gaze and diminishes on downward gaze, such that the lids smoothly follow vertical ocular versions; when testing for lid lag, the patient should be made to follow a moving target from above downward; any consistent lag, especially if unilateral, is prima facie evidence of Graves' ophthalmopathy.

Fig. 9. Normal lid positions. A. With the eyes in primary position, palpebral fissures are equal. Note the position of the lid margins with respect to the corneas. B. In conjugate lateral gaze, the lid fissure of the abducting eye may widen.

Fig. 10. S-shaped configuration of the right upper lid margin in neurofibromatosis, usually resulting from diffuse neurofibroma of the lid.


Abnormal elevation of the upper lid is seen in a variety of conditions, but it is most commonly associated with Graves' disease (Fig. 11). In this disorder, the exact mechanism of lid retraction is obscure, but it is probably not due simply to sympathetic overaction. In fact, if the upper lid margin or lashes are gently grasped, there is mechanical resistance to drawing the lid downward.

Fig. 11. Spectrum of lid retraction in dysthyroidism. A. Mild unilateral lid retraction. B. Moderate bilateral “stare.” C. Modest unilateral lid lag on downward gaze. D. Marked lid retraction in downward gaze.

Lid retraction is well documented in lesions involving the posterior third ventricle or rostral midbrian (Collier's sign of the posterior commissure). Fissure widening is increased on attempted upward gaze, which is also usually defective (Parinaud's syndrome), but lid position on downward gaze typically is normal (Fig. 12). Galetta and colleagues23 documented eyelid retraction and lid lag, with minimal impairment in vertical gaze, in patients with rostral midbrain lesions. Hydrocephalus in infancy is also thought to produce lid retraction via involvement of the periaqueductal area of the rostral midbrain.

Fig. 12. Pathologic lid retraction (Collier's sign) in rostral mesencephalic disorders. A. A patient with pinealoma. Note the position of the lids in forward gaze. The pupils are mid-dilated and light fixed. B. On downward gaze, the lids follow the eyes smoothly without retraction. C. A “setting sun” sign with lid retraction associated with infantile hydrocephalus.

Whereas topical instillation of sympathomimetic drugs is a well-recognized cause of lid retraction, only in rare instance do systemically administered agents result in lid position changes. Prolonged high doses of corticosteroids apparently cause lid retraction (in patients with normal thyroid function studies) in some cases24 (Fig. 13). Lid retraction has also been documented in cirrhotic patients without dysthyroidism.25

Fig. 13. Lid retraction in a patient taking long-term high doses of steroids for renal disease. All thyroid function studies are repeatedly normal.

Lid retraction may be seen with congenital anomalous synkineses, of which the Marcus Gunn jaw-winking phenomenon (Fig. 14A) is most widely known (see Volume 2, Chapter 13). Other congenital anomalous patterns are occasionally seen, such as lid retraction on downward gaze (Fig. 14B,C). The relationship of such anomalous synkineses with aberrant regeneration (misdirection) in the third cranial nerve is tenuous, because preceding oculomotor palsies have not been documented, and embryopathic miswiring is a more likely mechanism.

Fig. 14. Congenital lid retraction. A. Overaction of the levator (left) during the nonptotic phase of Marcus Gunn jaw-winking. B. Normal lid position in the forward eye position. C. Overaction of levator in downward gaze. (There is no history of birth trauma or other signs of third nerve misdirection.)

Bartley26 has suggested that lid retraction may be roughly classified as “neurogenic, myogenic and mechanistic”; this author also includes an extensive catalog of miscellaneous disorders purported to be associated with eyelid retraction.


The causes of lid ptosis are numerous, as outlined below, and the most common are discussed in sections dealing with the primary disorder (e.g., myasthenia, Horner's syndrome, oculomotor nerve palsies):

  1. Congenital ptosis
    1. Isolated
    2. With double-elevator palsy
    3. Anomalous synkineses (including Gunn jaw-winking)
    4. Lid or orbital tumor (hemangioma, dermoid)
    5. Neurofibromatosis (neurofibroma, neurilem-moma)
    6. Blepharophimosis syndromes
    7. First branchial arch syndromes (e.g., Hallermann-Streiff, Treacher Collins)
    8. Transient neonatal myasthenia (myasthenic mother)

  2. Myopathic ptosis
    1. Myasthenia
    2. Myotonic dystrophy
    3. Progressive external ophthalmoplegia (“ocular myopathy”)
    4. Familial variants of external ophthalmoplegias
    5. Graves' disease (rare; rule out myasthenia)

  3. Sympathetic oculoparesis (Horner's syndrome)
  4. Oculomotor nerve palsies
    1. Peripheral
    2. Central

  5. Miscellaneous
    1. Age-related levator dehiscence
    2. Allergic blepharochalasis; other recurrent lid edema
    3. Manipulation of levator complex: cataract, retina, corneal surgery
    4. Contact lenses, prolonged and long-term usage
    5. Orbito-facial trauma
    6. Lid and conjunctival infections/inflammations
    7. Obtundation, lethargy, drowsiness, intoxication
    8. Cortical (cerebral) “ptosis”
    9. Blepharospasm, hemifacial spasm, spastic contracture, facial nerve misdirection
    10. Apraxia of lid opening
    11. Hysteria or malingering

In the neonate, unilateral partial ptosis is only rarely due to birth trauma and is not likely to resolve on its own. Although occult tumors of the lid or orbit may be the hidden cause, nonetheless observation is usually the most prudent initial course in the neonate. Neurofibromatosis, for example, may present as ptosis without exophthalmos (see Fig. 9). Certainly before performing lid surgery in a young child, neuroimaging of the orbit and Tensilon testing should be accomplished. At any age, unexplained ptosis may eventually require a Tensilon test (Fig. 15A,B), but there are other observations and diagnostic maneuvers to uncover myasthenia. For example, levator fatigue may be demonstrated by observing slow lid curtaining during sustained upward gaze (usually, the lids become fatigued well before 1 minute). Cogan27 has described a useful “twitch” sign, which is elicited by having the patient rapidly redirect gaze from the downward to the primary position. The lid is seen initially to overshoot (twitch) upward and then slowly to resettle to the customary ptotic position. Occasionally, fine fluttering vibrations of the lash margins are observed in myasthenic lids. After brief eye closure, the relaxed myasthenic lid may momentarily recover before again drooping. A form of “pseudomyasthenia,” composed of fatigable ptosis with lid twitch that mimics myasthenia, even with improvement with acetylcholinesterase inhibitors, has been described in patients with skull base tumors and intrinsic brain stem tumors.28

Fig. 15. Myopathic ptosis. A and B. An elderly patient with “afternoon ptosis” and dramatic response to edrophonium chloride (Tensilon). C. A young boy with ptosis and the “hatchet face” of myotonic dystrophy.

Ptosis may be familial, or it may occur as a symmetric, slowly progressive disorder of senescence. Before contemplating surgical repair of ptotic lids, it is critical to establish the state of upward deviation of the globes. With defective upward gaze, as occurs in progressive external ophthalmoplegia (see Volume 2, Chapter 12, Figs. 31 and 32), serious corneal complications due to exposure may follow ptosis surgery.

In cases of newly acquired unilateral ptosis, the size and reactivity of the ipsilateral pupil usually establish whether sympathetic or oculomotor paresis is present. Abrupt or progressive ptosis occurring without pain or pupillary abnormality, or alternating sides, is likely to be myasthenic in origin. The levator muscle-aponeurosis complex seems especially sensitive to mechanical processes that may take the form of trauma, including manipulation during common ophthalmic surgical procedures (for cataract, retinal detachment, or any procedure that includes the placement of a lid speculum or other disturbance of the superior rectus muscle, the latter being intimately attached to the levator). Traumatic (including the foregoing) weakening of the levator complex may follow even mild injury, and age alone takes its toll on the lids. Involutional, otherwise idiopathic, ptosis is related to the following: sagging and redundancy of lid and brow tissues; weakening and dehiscences of levator fascial attachments to the tarsus; medial dehiscence of Whitnall's ligament; focal levator atrophy (primary myopathy ?); and prolapse of retro-septal fat.29

Of special note in younger patients, prolonged wearing of hard contact lenses distinctly may cause ptosis, usually asymmetric, which may be due to levator disinsertion.30 However, in my experience, the lid slowly recovers after several weeks of lens discontinuance, a finding that suggests a reversible mechanism such as reactive edema. Ptosis and lagophthalmos suggest infiltration of the lids by tumor such as breast carcinoma,31 which may also be accompanied by enophthalmos (see Volume 2, Chapter 14, Fig. 9A-C).

Confused with genuine ptosis is apraxia of lid opening, an inability volitionally to open the eyes that is not due to infranuclear paralysis or myopathy. The syndrome variably keeps company with extrapyramidal system disorders such as parkinsonism, progressive supranuclear palsy, and multiple system atrophy.32 At times, this disabling condition may be associated with blepharospasm, although simple involuntary levator inhibition without hyperactive facial movement permits sudden release of apparently immobile lids; thus, the somewhat inaccurate term “apraxia” is applied. The precise nature of the central defect is unclear, and specific therapies are not yet clarified (see Volume 2, Chapter 8).


Upper lid nystagmus is a pathologic condition when not part of synchronous vertical beating ocular nystagmus, that is, when the lid jerking does not simply reflect movement secondary to eye displacement. It is a rare observation, usually evoked by convergence (Pick's sign) or by horizontal conjugate gaze. It has been reported in patients with multiple sclerosis, cerebellar diseases, cranial polyneuropathy (Miller Fisher syndrome), and midbrain astrocytoma.33 Lid nystagmus is usually accompanied by other neuro-ophthalmologic findings such as ptosis, ophthalmoparesis, gaze-evoked nystagmus, and dorsal midbrain or cerebellar signs.

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Pain in and about the eye is a compelling symptom that the patient cannot ignore and the physician cannot dismiss. Most eye pain is indeed due to ocular disease, most of which is diagnosed by ophthalmologic evaluation. Diminished sensation, on the other hand, is a relatively rare finding and an even less frequent complaint. However, the symptoms of pain or numbness in the trigeminal distribution deserve careful consideration as a neuro-ophthalmologic signal.


The sensory innervation of the globe is mediated through the ophthalmic division (V1) of the fifth cranial nerve (trigeminal) (Fig. 16). The anterior ocular segment, including the cornea, iris, trabecular meshwork, and ciliary body, transmits pain, temperature, and touch sensations via the ciliary nerves, which join the nasociliary nerve directly (long ciliary nerve) or by traversing the ciliary ganglion (short ciliary nerves). Nerve endings contain neuropeptide vesicles, and antidromic stimulation of the trigeminal nerve causes release of neuropeptide into the aqueous that provokes uveal vasodilation and an inflammatory response;34 that is, the sensory trigeminal exerts an “ocular injury response” by modulating parasympathetic neurons in the pterygopalatine ganglion.35 The role of minute sympathetic innervation to the cornea is obscure. Other branches of the nasociliary nerve supply sensation to the upper lid skin and conjunctiva, caruncle, medial canthus, lacrimal sac, bridge of the nose, nasal mucosa, and tip of the nose.

Fig. 16. Top. Trigeminal-sensory complex. Ocular and facial sensation is mediated by the trigeminal nuclear complex, which extends from the midbrain downward into the upper cervical segments (C1 through C4). The rostral nucleus (MESencephalic) serves proprioception and deep sensation from the tendons and muscles of mastication. Axons of afferent cells also terminate in the motor nucleus (MN) of the trigeminal, which innervates the masticatory muscles (dotted line) via the mandibular division. The midportion of the trigeminal complex contains the chief sensory nucleus (CSN) located in the pons. This nucleus serves light touch from the skin and mucous membranes. Without a distinct transition, the nuclear complex continues caudally as the spinal nucleus (SPN), which receives pain and temperature afferents via the descending spinal tract (DST); cutaneous sensory components of 7, 9, and 10 also join the spinal tract, conducting sensation from the ear and external auditory meatus. Concentric areas of the face (A, B, and C) are projected on corresponding portions of the caudal aspect of the spinal nucleus. The corneal reflex is mediated via internuclear fibers to the facial nuclei. The fibers ascend to the thalamus via the ventral (VTT) and dorsal trigeminothalamic (DTT) tracts; an ipsilateral ascending DTT tract is not shown. The gasserian ganglion (GG) contains cell bodies of neurons mediating touch, pain, and temperature from three trigeminal divisions; cell bodies for proprioception and deep pain are contained in the MES. Cross-section of the pons at the level of the trigeminal roots includes the fourth ventricle (V-4), the median longitudinal fascicule (MLF), and the medial lemniscus (LEM). Bottom. Peripheral trigeminal distribution. Three major divisions arise from the gasserian ganglion (GG). The ophthalmic (I) enters the cavernous sinus (shaded area CS) lateral to the internal carotid artery (CAR), passes into the orbit via the superior orbital fissure (SOF), and divides into the frontal (FR), lacrimal (LA), and nasociliary (NC) branches. The supraorbital (SO) nerve supplies the medial upper lid and the conjunctiva, forehead, scalp, and frontal sinuses; the supratrochlear nerve (ST) supplies the conjunctiva, medial upper lid, forehead, and side of the nose. The lacrimal nerve (LA) serves the conjunctiva and skin in the area of the lacrimal gland (lateral palpebral branch, LP) and carries post-ganglionic parasympathetic fibers (dotted line) for reflex lacrimation. Pre-ganglionic fibers traverse the vidian canal with the greater superficial petrosal nerve (GSP) and enter the sphenopalatine ganglion (SPG), thence to the maxillary nerve, which transmits post-ganglionic fibers to the lacrimal nerve via an anastomosis, the zygomaticotemporal nerve (ZT). The nasociliary (NC) branch of the ophthalmic nerve supplies sensation to the globe. A series of nasal nerves (NAS) serves the mucosa of nasal septum, middle and inferior turbinates, and lateral nasal wall. An external nasal (EN) branch innervates skin of nose tip. The infratrochlear (IT) branch supplies the canaliculi, caruncle, lacrimal sac, conjunctiva, and skin of the medial canthus. Two long ciliary (LC) nerves carry sensory fibers from the ciliary body, iris, and cornea, and sympathetic innervation to the pupil dilator. Multiple short ciliary (SC) nerves transmit sensory fibers from the globe that pass through the ciliary ganglion (CG) and join the nasociliary nerve via its sensory root; short ciliaries also carry post-ganglionic parasympathetic fibers (dotted line) from the ciliary ganglion to the pupil constrictor and ciliary muscle. These fibers reach the ciliary ganglion via the inferior division of the oculomotor nerve (OM) destined to innervate the inferior oblique (IO) muscle. The maxillary division (MAX, II) does not usually traverse the cavernous sinus, but exits the skull through the foramen rotundum (R) into a variable “trigeminal” sinus, thence into the pterygopalatine fossa in relation to the sphenopalatine ganglion, thence into the inferior orbital fissure, continuing along the orbital floor into the infraorbital canal (IOC). The posterior, middle, and anterior superior alveolar nerves (SAN) supply the upper teeth, maxillary sinus, nasopharynx, tonsils, soft palate, and roof of the mouth. The infraorbital nerve exits onto face through infraorbital foramen, supplying the lower lid via the inferior palpebral (IP), side of the nose via the nasal (NA), and upper lid via the superior labial (SL) nerves. A zygomaticofacial (ZF) innervates side of cheek. The mandibular (III) is the only mixed motor-sensory division of the trigeminal. Both roots pass through the foramen ovale (O) into the infratemporal fossa; the motor branches supply the pterygoid, masseter, and temporalis muscles; the sensory branches supply the mucosa and skin of the mandible and lower lip, tongue sensation, external ear, and tympanum. A tentorial-dural branch (TD) arises from the intracavernous portion of the opthalmic, to supply sensation to the dura of the cavernous sinus, anterior fossa, sphenoid wing, petrous ridge, trigeminal cave (Meckel's), tentorium cerebelli, posterior aspect of falx cerebri, and dural venous sinuses. Sensation from cerebral veins and arteries, as well as nerves III, IV, and VI, may be mediated by these dural nerves.

The upper lid and its conjunctiva, as well as the brow, forehead, and scalp, are supplied by the supratrochlear and supraorbital branches of the frontal nerve. The temporal aspect of the upper lid and outer canthus is supplied by the lateral palpebral branch of the lacrimal nerve, and the lower lid is in the sensory distribution of the infraorbital nerve of the maxillary division (V2) of the trigeminal nerve (Fig. 17).

Fig. 17. Cutaneous sensory distribution of the trigeminal nerve: 1, ophthalmic; 2, maxillary; 3, mandibular divisions.

The nonocular distribution of the ophthalmic division is of major clinical importance because disturbances of intracranial structures, including dura, dural venous sinuses, cerebral arteries and veins, all typically refer pain to the eye, orbit, or brow. Referral of pain from dural stimulation was reviewed by Wirth and van Buren,36 who found that pain patterns secondary to intracranial disease were not sufficiently specific to provide precise clinical localization.

Peripheral Trigeminal Afferents

The trigeminal nerve conveys pain and mechanoreceptor afferents from the intracranial dura, except the infratentorial dura of the posterior fossa, from which afferents are carried by the vagus. There are vagal somatosensory afferent fibers that run in the spinal tract of the trigeminal and synapse with cells in the spinal nucleus; although the vagus is the peripheral nerve, the central connections are essentially trigeminal. Cell bodies for the peripheral trigeminal fibers and for the primary nociceptive and other afferents are situated in the gasserian ganglion in Meckel's cave at the base of the sphenoid bone (see Volume 2, Chapter 12, Figs. 5 and 20). Cells here vary in size; the smaller (C-nociceptors) synapse in the caudal end of the spinal nucleus, which is consonant with clinical evidence that pain results mainly from lesions in the caudalmost part of the spinal nucleus and tract. In addition, there is layering of the inputs in the spinal tract: the ophthalmic fibers that terminate caudally are ventral; the maxillary division fibers end in a more dorsal and rostral layer; and the mandibular division fibers insert above the maxillary layer. Dorsal to three trigeminal layers in the spinal nucleus are pathways served peripherally by cranial nerves IX, X, and the facial intermedius (VIIi).

Trigeminal Sensory Nuclei

The spinal nucleus is an area of sensory integration, as evidenced by the presence of ascending spinal cord afferents37 and descending fibers primarily from contralateral somatosensory cortex, but also with inputs from the red nucleus, the reticular formation, and of course the primary trigeminal afferents. The spinal tract and nucleus descend to the level of C2 to C4 and merge with the dorsal horn of the spinal gray matter. In fact, the histologic organization of the trigeminal spinal tract pars caudalis is strikingly similar to that of the dorsal horn. There are three layers: an outer marginal zone occupied by large Waldeyer-type cells; a gelatinous layer; and a deeper subnucleus magnocellularis. In the more rostral parts of the spinal nucleus (the interpolaris and the rostralis subnuclei), the histologic organization differs from the caudalis portion. This suggests functional specialization even within the spinal tract, in which the caudalis part is homologous to the dorsal horn pain-carrying system, and the oralis subnucleus is homologous with the nuclei of the dorsal columns, carrying non-nociceptive touch and mechanoreceptor sensation.

Trigeminal Ascending Pathways

Afferents from the main sensory nucleus travel in the contralateral medial-dorsal portion of the medial lemniscus (trigeminal lemniscus) to the ventral postero-median nucleus of the thalamus. A smaller uncrossed output from the dorsal part of the main sensory nucleus ascends to the dorsomedial part of the ipsilateral ventral postero-median nucleus. Outflow from the pars caudalis of the spinal nucleus probably runs or originates in the reticular formation. Horseradish peroxidase injections into the thalamus have revealed labeled cells in the reticular formation adjacent to the pars caudalis, as well as labeled units in the marginal zone of the spinal nucleus itself.38 This situation suggests a certain similarity with the dorsal horn output, some of which goes directly to the thalamus in the spinothalamic tract, and some goes indirectly via spinoreticular and spinomesencephalic tracts. The caudal spinal trigeminal nucleus input to the thalamus is scanty, according to many of the anatomic studies. Perhaps available methods underestimate these afferents, there being possibly a greater number of polysynaptic neural chains rather than direct monosynaptic inputs from the caudal spinal nucleus. Moreover, physiologic studies indicate that units in the main sensory nucleus, in addition to caudalis spinal nucleus units, respond to tooth-pulp stimulation. Thus, there appears to be duality of nociceptive input, with ascending and descending collaterals from fibers entering via the trigeminal sensory root innervating both the main sensory and the spinal nuclei.


Sensory testing of the globe and face may be accomplished rapidly and without need for special equipment. Corneal sensation obviously cannot be adequately evaluated after instillation of topical anesthetics for intra-ocular tension measurements. In clinical practice, pain sensation is routinely assessed rather than other sensory modalities. In the otherwise intact patient, both subjective and objective responses may be evaluated. In the lethargic or obtunded patient, blink reflex and head withdrawal are gross objective signs of corneal sensitivity.

In office practice, an applicator with a cotton tip drawn to a point (Fig. 18) may be lightly touched to, or drawn across, the inferior aspect of the cornea. In ocular inflammatory disease, the same cotton probably should not be used in both eyes (e.g., with herpes simplex keratitis). The applicator cotton wisp may also be used to test light touch sensation of the brow and face, looking for differences from one side of the midline to the other. Such cutaneous sensory testing is best accomplished with the patient's eyes closed, the response indicating which side of the face has been touched. Subjective and objective responses to eye drop instillation are useful indications of relative corneal sensation.

Fig. 18. Examination of corneal sensation. A. The patient has a right intracavernous aneurysm and an insensitive right cornea that “permits parking” of a cotton-tipped applicator. B. When the cotton wisp is gently placed on the left cornea, a blink occurs, and the patient subjectively indicates discomfort.

The motor function of the mandibular division is conveniently tested by palpating masseter mass (over the rami of the madibles) and temporalis muscle bulk during the command, “Grit your teeth.” Pterygoid function may be assessed by having the patient attempt to deviate the jaw laterally against the palm of the examiner's hand (weakness toward the right indicates palsy of left pterygoid group).


The causes of diminished sensation in the trigeminal distribution are outlined below:

  1. Cornea
    1. Herpes simplex
    2. Ocular surgery
    3. Cerebellopontine angle tumors
    4. Dysautonomia
    5. Congenital

  2. Ophthalmic division
    1. Neoplasm, orbital apex
    2. Neoplasm, superior orbital fissure
    3. Neoplasm, cavernous sinus
    4. Neoplasm, middle fossa
    5. Aneurysm, cavernous sinus

  3. Maxillary division
    1. Orbit floor fracture
    2. Maxillary antrum carcinoma
    3. Perineural spread of skin carcinoma
    4. Neoplasm, foramen rotundum, sphenopterygoid fossa

  4. Mandibular division
    1. Nasopharyngeal tumor
    2. Middle fossa tumor

  5. All divisions
    1. Nasopharyngeal carcinoma
    2. Cerebellopontine angle tumors
    3. Brain stem lesions (dissociated sensory loss)
    4. Intracavernous aneurysm
    5. Demyelinative
    6. Middle fossa or Meckel's cave tumor
    7. Benign sensory neuropathy
    8. Tentorial meningioma
    9. Toxins (e.g., trichlorethylene)
    10. Trigeminal neurofibroma

In addition to hypesthesia, corneal sensory testing may uncover other abnormal reflexes. For example, the motor arc (facial nerve) of the corneal reflex may be absent or diminished. Both the afferent (pain) and efferent (blink) portions of the reflex may be diminished, as in patients with cerebellopontine angle tumors.

A corneo-mandibular reflex may be seen in patients with bilateral corticobulbar tract lesions, either hemispheral or at the midbrain level, or in parkinsonism. When the cornea is stimulated, the jaw momentarily deviates to the opposite side, concurrent with eye closure. As pointed out by Paulson and Bird,39 the corneo-mandibular reflex is quite common in normal infants, contrary to Wartenberg's opinion. Therefore, this infantile reflex may “return” in cerebral and extrapyramidal diseases of senescence.


The causes of eye pain are numerous and consist, for the most part, of diseases of the globe and ocular adnexa. However, discomfort in the ocular segment or orbit may be a harbinger of neurologic disease ranging from innocent vascular cranial mononeuropathies (e.g., diabetic ophthalmoplegia) to bleeding aneurysm, sinus inflammation, or atypical migraine (see Volume 2, Chapter 16). An outline of relatively common entities associated with ocular and facial pain is presented below. Painful ophthalmoplegia syndromes are discussed in Volume 2, Chapter 12.

  1. Ocular
    1. Local lid, conjunctival, and anterior segment disease
    2. Ocular inflammation
    3. Dry eye and tear deficiency syndromes
    4. Chronic ocular hypoxia, carotid occlusive disease
    5. Angle-closure glaucoma

  2. Ophthalmic division
    1. Migraine, cluster headaches
    2. Raeder's paratrigeminal neuralgia
    3. Painful ophthalmoplegia syndromes
    4. Herpes zoster
    5. Referred (dural) pain, including occipital infarction
    6. Tic douloureux (infrequent in V1)
    7. Sinusitis

  3. Maxillary division
    1. Tic douloureux
    2. Nasopharyngeal carcinoma
    3. Temporo-mandibular joint syndrome
    4. Dental disease
    5. Sinusitis

  4. Mandibular division
    1. Tic douloureux
    2. Dental disease

  5. Miscellaneous
    1. Atypical facial neuralgias
    2. Pain with medullary lesions
    3. Cranial arteritis
    4. Trigeminal tumors

Many patients, especially middle-aged and elderly women, complain of vague aches, “stabs,” and other discomfort in and about the eyes. Neither ocular nor neurologic disease is demonstrable, although the patient often anticipates that a grave cause will be uncovered. Often, nonspecific symptoms are considered due to “eyestrain,” the need for new spectacle lenses, or exposure to lights (especially fluorescent) or to the elements. Having examined the patient and determined that no substantial disease is present, the quantity and quality of the tear film must be suspect. Dry eye syndrome (keratoconjunctivitis sicca) consists of the following: foreign body sensation with “gritty” feeling, itching, burning, redness, and excessive tearing (epiphora); photophobia; reduced tear meniscus, abundant mucous threads, debris in the precorneal tear film, and hyperemic palpebral and conjunctival conjunctiva; rapid (less than 10 seconds) breakup of the fluorescein-stained tear film over the cornea and rose-bengal staining of the interpalpebral conjunctiva; Schirmer strip test typically showing minimal wetting.40,41 In women especially, there is an age-related progressive loss of tear film constituents that ordinarily keep the eyes lubricated and comfortable, and dry mouth is also common.

Patients with secretory dysfunction of the lacrimal gland develop pathologic changes of the corneal epithelium, squamous metaplasia. Epithelial cells reflect inflammation, fail to mature, and no longer produce the mucus that normally coats and lubricates the ocular surfaces. Thus, some patients with “dry eye” experience both ocular irritation and, occasionally, visual disturbance that may be mistaken for occult neurologic disease.

Many patients with vague ocular discomfort and nonspecific findings are made comfortable by the following regimen: (1) eye and facial cosmetics are cut to the minimum; (2) hair “stiffeners” with shellac bases must be discontinued; (3) on arising, at midday, and before retiring, a basin of warm water with a few drops of baby shampoo is used with a washcloth to cleanse the brows, lids, and lashes thoroughly; and (4) as needed for comfort, but at least four times per day, a tear substitute is instilled.


In general, defective lacrimation is an uncommon problem in neuro-ophthalmology. This finding is usually encountered in the context of diminished corneal sensation subsequent to local corneal disease (including herpes zoster, keratitis), to neurosurgical lesions of the ophthalmic division (ganglion or sensory root), or to medullary infarction. Reflex tearing is diminished in the presence of a hypesthetic cornea, and severe complicated keratitis may develop (neuroparalytic keratitis). If facial nerve function is also defective such that some degree of corneal exposure occurs, the keratitis is usually even more severe.

Reflex tearing, that is, that evoked by trigeminal sensory stimulation, is mediated by pre-ganglionic parasympathetic fibers that arise near the facial nucleus in the pontine tegmentum. These fibers exit the brain stem and travel with the sensory root (nervus intermedius) of the facial nerve (see Volume 2, Chapter 8), traverse the geniculate ganglion, and enter the greater superficial petrosal nerve, which lies in the floor of the middle fossa in a position lateral to the trigeminal ganglion (gasserian). After joining the deep petrosal nerve to form the vidian nerve, the pre-synaptic fibers enter the sphenopalatine ganglion, where they synapse with post-ganglionic fibers. These latter fibers gain the lacrimal gland by joining the zygomatic branch of the maxillary division of the trigeminal (see Fig. 16).

The efferent limb of reflex tearing may be interrupted by lesions involving the facial nerve in the cerebellopontine angle or petrous bone, the greater superficial petrosal nerve in the floor of the middle fossa, or the sphenopalatine ganglion in the retro-antral space. The onset of facial pain or numbness associated with a sixth nerve palsy (medial aspect of middle fossa) and deficient tearing, or numbness in the maxillary division with diminished tearing, are syndromes typical of malignant nasopharyngeal tumor. Defective reflex tear secretion is assessed semiquantitatively by Schirmer filter paper technique, without application of topical anesthetics.

Paradoxical tearing may occur months following facial palsies, wherein the anticipation or taste of food provokes excessive tearing. This gustatory-lacrimal reflex (“crocodile tears”) is caused by misdirection of regenerating salivary axons in the proximal portion of the facial nerve that then aggrandize the peripheral pathways to the lacrimal gland. On rare occasions, this autonomic dyskinesis is congenital and has been reported in Duane's retraction syndrome (see Volume 2, Chapter 8).


Most ocular pain is caused by actual pathologic changes observable in or on the globe, or with evidence of adnexal or orbital disease. Gritty or sandy sensations, made worse with blinking or eye movement, usually accompanied by copious tearing, surely point to foreign body of the cornea or hidden under the lid. Fluorescein staining of the cornea with slit-lamp examination is indicated. Most, but not all, “red eyes” are caused by local infections or inflammations. Iritis (anterior uveitis) is usually accompanied by photophobia and evidence of anterior chamber cells and protein flare. The “dry eye” and its symptoms, and the vagaries of “eyestrain” (asthenopia), are considered above. With regard to the question of “eyestrain” and ocular neuroses, in 1930, Derby42 quipped: “I wish we could banish the term eyestrain from our vocabulary. If the general public could learn that the eyes are seldom strained, this would be a much happier world to live in. . . . Eyestrain is a terrible and serious bugbear to the public; would that the word had never been coined.” At any rate, these conditions are all strictly the business of the ophthalmologist.

The subject of painful ophthalmoplegia is covered at length in Volume 2, Chapter 12, and orbitopathies are discussed in Volume 2, Chapter 14. Table 1 is a brief outline emphasizing neuralgias and atypical facial pain syndromes, which are not to be confused with standard headache syndromes or the variants of migraine.


TABLE 1. Pain In and About the Eye


  Cornea and conjunctival inflammations, foreign body, “dry eye”
  Blepharitis, chalazion, scleritis, episcleritis
  Anterior uveitis, angle-closure glaucoma, chronic ocular ischemia
  Accommodative spasm, convergence insufficient; ? refractive errors
  Graves' disease, inflammatory pseudotumor, other congestive orbitopathies


  Herpes zoster ophthalmicus
  Trigeminal neuralgia
  Infiltrative (perineural) neuralgias

  Atypical facial pain

  Temporo-mandibular joint syndrome
  Dental malocclusion
  Cluster headaches
  Sinus disease
  Giant cell (cranial) arteritis
  Carotid dissection
  Occult perineural infiltration


Herpes zoster (from the Greek herpein, to spread, and zoster, girdle or zone) ophthalmicus is a common cause of first trigeminal division acute pain and more-or-less simultaneous or slightly delayed cutaneous vesiculation (Fig. 19), followed by pustule formation. The infection occurs in otherwise healthy persons, but with increasing frequency in immunocompromised patients, including those with malignancies and especially in acquired immunodeficiency syndrome.43 After primary varicella infection (chickenpox), the virus lies dormant in the sensory trigeminal ganglion, until the virus is reactivated as zoster. An inflamed eye with dendritiform keratopathy and iritis is frequent, but it is the disabling post-herpetic neuralgia that constitutes the major challenge in pain control. The risk of post-herpetic neuralgia increases with age.

Fig. 19. Herpes zoster ophthalmicus involving the first (ophthalmic) division of right trigeminal nerve distribution. Note ptosis and lid edema; the pupil is dilated to relieve iritis pain. Note involvement of the nose (arrows).

Corticosteroids by systemic administration and antiviral agents such as oral or intravenous acyclovir or famciclovir are reported to ameliorate acute pain significantly and arguably to reduce the likelihood of neuralgia.44 Zoster of the geniculate ganglion, the Ramsay Hunt syndrome, results in ear and facial vesiculation, pain, and facial palsy (see Volume 2, Chapter 8, Fig. 10), as discussed in Volume 2, Chapter 8. Abducens, trochlear, and oculomotor nerve palsies are reported, as well as Horner's syndrome and optic neuritis.45

Trigeminal neuralgia is characterized by episodic, recurring electric shock-like or lancinating (knife-like) pain of severe magnitude, often triggered by stimulation of facial cutaneous areas or mucous membranes of the oral cavity. Usually of idiopathic origin, trigeminal neuralgia also occurs in patients with tumors or vascular compression at the trigeminal root exit zone,46 and infrequently in patients with multiple sclerosis.47 Trigeminal neuropathy implies prominent sensory loss, in which case an infiltrative, inflammatory, or compressive cause must be explored.48

Cutaneous carcinomas of the face, and some nasopharyngeal carcinomas, may present with facial dysesthesias (“ants crawling,” formication), pain, or numbness, at times associated with facial nerve palsies or unilateral ophthalmoplegia. Centripetal perineural spread may eventually carry the disease to the cavernous sinus. Magnetic resonance imaging can disclose involved peripheral trigeminal nerve branches, for example, the infraorbital nerve, that may be biopsied.49 A past history of treatment for facial carcinoma, especially squamous cell, is highly suggestive of this diagnosis.

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Although the diagnosis and treatment of coma are the purview primarily of the neurologist and neurosurgeon, the ophthalmologist may at times be of great help in the analysis of eye-movement patterns, state of the pupils, and condition of the fundus. Indeed, the neurologist or neurosurgeon also must be conversant with the neuro-ophthalmologic assessment of the patient who cannot respond. Local disorders of the globe and the ocular adnexa must first be excluded. These possibilities include the following: pre-existing pupillary abnormalities such as surgical aphakia (we have seen arteriography performed on a comatose patient because of a “dilated pupil,” which actually was unilateral aphakia with a sector iridectomy); miosis due to glaucoma medication; and anterior segment inflammation with iris adhesions. In patients with trauma, orbital fractures may limit eye movement, and mydriasis may be due to direct blunt injury to the globe and may not signify oculomotor palsy.

The “swinging flashlight test” may be used to evaluate the afferent and motor pathways of the anterior visual system. It should be re-emphasized that anisocoria cannot be due to a strictly afferent defect (e.g., optic nerve contusion) (see Volume 2, Chapter 15). Eyelid blink to sudden bright illumination may be mediated through subcortical reflexes50 and may not be taken to indicate intact cerebral pathways.

In general, in patients with metabolic coma or drug overdose, the pupils are small but reactive, in keeping with depression of the reticular activating system and removal of its inhibition of the pretectal center for pupillary constriction. Such miotic pupils (“pontine miosis”) may dilate momentarily with pain or other psychosensory stimuli. In the terminal (anoxic) stage of metabolic encephalopathies, pupillary dilation occurs and is considered a grave prognostic sign. Paulson and Kapp51 suggested that such pupillary widening in cerebral ischemia is due to massive sympathetic discharge.

A dilated and fixed pupil may herald progressive third nerve palsy due to temporal lobe herniation (Hutchinson's pupil) occurring with hemispheral mass lesions (e.g., subdural hematoma). Injury of the third nerve sustained at the time of head trauma is usually complete and nonprogressive, as is oculomotor palsy due to bleeding intracranial aneurysm, although instances of isolated pupillary paresis are reported (see Volume 2, Chapter 12).

Examination of ocular motility in the comatose patient requires special maneuvers. It is first necessary to note spontaneous eye movement, more specifically, the range of movement of each eye, the degree of coordinated movement of the two eyes, and any intermittent or continuous pattern of eye movement. Various degrees of nonconjugate eye movements are to be expected in patients in a coma. In cases of drug intoxication or simple concussion, surprisingly incoordinate and erratic slow wandering of the eyes may be observed. These movements themselves neither signify major brain stem damage nor portend a lasting or disastrous neurologic deficit. Note should be made of persistent tonic deviation or lack of spontaneous movement in a particular direction. Further details of specific eye movements in coma (e.g., ocular bobbing) are discussed in Volume 2, Chapter 11.

In the comatose, obtunded, or lethargic patient, voluntary or visually evoked eye movements cannot be evaluated. Other than spontaneous movements, the ocular motor system may be analyzed by reflex ocular deviations: rotational, oculocephalic, and caloric stimulation.Rotational testing is of no practical value in the comatose patient (other than perhaps an infant). The oculocephalic (doll's head, Roth-Bielschowsky deviation) reflex is dependent on stimulation of the vestibular system by rapid passive head turning, with an anticipated contraversive conjugate eye movement. For example, if the examiner suddenly rotates the head of a comatose patient toward the left (Fig. 20), the eyes will move contraversively to the right, if pontine gaze mechanisms are intact. These oculocephalic versions may be of relatively short duration, but they provide a rapid approximation of brain stem function. Vertical movements may similarly be tested by rapid extension and flexion of the head.

Fig. 20. Examination of ocular motor function in a comatose patient.

In patients with cerebral and brain stem hemorrhages or increased intracranial pressure, one may argue against the advisability of maneuvers entailing rapid displacement of the head, and certainly such abrupt rotations are contraindicated in cervical injuries. By contrast, as Rodriguez-Barrios52 pointed out, caloric stimulation of the labyrinth is a harmless, simple procedure that may be repeated at will. Caloric irrigation of the ear canal cannot be carried out on the side of an otorrhagia from basal skull fracture, and this complication should first be excluded by otologic examination.

The technique of caloric testing may be simplified for bedside diagnosis by using available sources, either cool tap water or ice water. The external canal and tympanum should first be inspected, and wax or other debris should be removed. With the patient's head on a pillow, that is, at an angle of 30° with the horizontal (for maximum stimulation of the horizontal semicircular canals), 10 ml to 20 ml of cold water is flushed into the ear canal using a small rubber tube fitted onto a syringe (see Fig. 20; Fig. 21B). One of several responses may be observed: (1) a slow tonic ocular deviation toward the side of cold irrigation (a bilateral positive response indicates integrity of pontine oculogyric mechanisms); (2) nystagmus, with the jerk phase directed away from the side of cold irrigation (usually the eyes drift toward the side of irrigation, but the nystagmus beats toward the opposite side); (3) no deviation elicited (total abolition of responses to caloric labyrinthine stimulation usually corresponds to an extensive pontine lesion); (4) vertical responses preserved in the absence of horizontal movement, indicating relative sparing of the midbrain (upward deviation is tested by bilateral irrigation with warm water, and downward tonic deviation attempted by bilateral cold water instillation); and (5) an ocular motor nerve palsy (III or VI) further elucidated by observing one eye responding while the other does not, an internuclear ophthalmoplegia may be uncovered.

Fig. 21. Ocular signs in coma. A patient with barbiturate overdose shows no ocular motor response to doll's head maneuver (A) or cold caloric irrigation (B). C. Pupils are small but reactive, and the eyes are slightly divergent. D. A patient with a right frontoparietal infarct demonstrates tonic deviation of the eyes to the right.

In barbiturate intoxication with coma, all oculocephalic and vestibulo-ocular reflexes may be temporarily lost (see Fig 21). Similar cases with phenytoin alone or in combination with primidone have been reported.53

Table 2 provides an overview of ocular signs in the comatose patient. A complete discussion of neurologic signs in coma is available in the text by Plum and Posner.54


TABLE 2. Ocular Signs in Coma

Extraocular Movements 
Level of ImpairmentRest PositionDoll's HeadCold CaloricsDefective SystemPupils
Unilateral hemispheralTonic deviation toward lesionIntact*Intact*Frontomesen-cephalic (saccadic)In hemispheral disease pupillary signs inconstant and usually of little help; in coma, pupil usually small but reactive
Bilateral or diffuse hemispheralStraight/ divergent; slow disconjugate wanderingIntact*Tonic phase onlyBilateral fronto-mesencephalic  
Metabolic, in-cluding drugs      
LightStraight/ divergentIntact*/diminishedIntact*/diminished(Above)SmallReactive
DeepSlow disconjugate wandering or fixedAbsentAbsentBrain stem -reticular  
Straight or skew; ± IIIHorizontal only;adduction lagHorizontal only;adduction lag; ± skewRostral mesen-cephalic vertical gazeMid-dilated; ± IIIFixed 
PonsStraight or deviated opposite lesion; ± skew; ± bobbingMay fail to one/both sides; ± internuclear; ± VIMay fail to one/ both sides; ± internuclear; ± VIPontine paramedian reticularPinpointReactive
EarlyDeviated opposite lesion; gaze palsy toward lesionNormal or diminished toward side of gaze palsyNormal or diminished toward side of gaze palsy?(Normal) 
Late± SkewDiminished/ absent toward side of gaze palsyDiminished/ absent toward side of gaze palsyPinpointReactive 

*Bilaterally intact doll's head or caloric deviations preclude the possibility of severe pontine lesions.
(The onset of reflex paralysis of eye movements in the course of coma is considered a sign of secondary brain stem hemorrhages.)
In coma, eyes directed straight have no localizing value.
‡The syndrome of acute cerebellar hemorrhage consists of occipital headache, ataxia, vertigo, conjugate gaze palsy, and progressive lethargy.


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