Neuro-Ophthalmology: Ocular Motor System PDF

18 Neuro-Ophthalmology: Ocular Motor System...

18 Neuro-Ophthalmology: Ocular Motor System Janet C. Rucker, Patrick J.M. Lavin OUTLINE General Principles of Ocular Motor Control, 201 Disorders of Eye Movements—Abnormal Spontaneous Movements Eye Movement Anatomy, 201 and Oscillations, 227 Functional Classes of Eye Movements, 201 Approach to History and Examination, 227 The Final Common Pathway of Eye Movements, 206 Clinical Disorders, 228 Disorders of Eye Movements—Ophthalmoplegia and Ocular Mis- Treatment of Oscillations, 239 alignment, 206 Development of the Ocular Motor System, 239 Approach to History and Examination, 206 Recording of Eye Movements, 240 Localization and Diagnosis, 212 How can they help? 240 Treatment of Diplopia, 227 Methods of Recording, 240 GENERAL PRINCIPLES OF OCULAR MOTOR the magnocellular layer of the LGN. In turn, LGN neurons project via the CONTROL optic radiations to the primary visual area (V1), the striate cortex (area 17). From here, two processing streams project (Fig. 18.1): the ventral I do not know of any kind of work better fitted for correcting loose stream, responsible for form and object recognition dominated by foveal habits of observation and careless thinking than a study of the ocu- representation, projects to the temporal lobe; the dorsal stream, responsi- lar motor nerves. ble for movement recognition and visuospatial processing dominated by John Hughlings Jackson, 1877 peripheral visual field representation, projects to the prestriate cortex and then to the superior temporal sulcus region. This contains cortical middle This chapter includes an outline of ocular motor anatomy and physi- temporal (MT) areas and middle superior temporal (MST) areas in mon- ology pertaining to clinical disorders of eye movements and is divided keys, roughly equivalent to the parietotemporal-occipital (PTO) junction into two broad categories: those disorders that result in insufficient in humans. Both streams converge on the frontal eye fields (FEFs) and eye movements and ocular misalignment, thereby causing disorders of are involved in controlling saccades and other eye movements. Thus, with gaze and binocular diplopia, and those that result in abnormal spon- the exception of reflexive vestibular eye movements, cerebral structures taneous eye movements, causing a subjective sense of visual motion determine when and where the eyes move, whereas brainstem mechanisms called oscillopsia. Competence in accurate diagnosis in such disorders determine how they move. In other words, voluntary eye movements are is dependent on the skills of attentive listening, probing questions, generated in the brainstem but triggered by the cerebral cortex. extensive knowledge of neuroanatomy and of disorders that affect the efferent visual pathways, and eye movement examination. Objective EYE MOVEMENT ANATOMY measurement of abnormal eye movements can increase the sensitivity of detecting subtle deficits to confirm clinical suspicions. Functional Classes of Eye Movements A reasonable understanding and interpretation of abnormal eye move- The goal of visual fixation and all normal eye movements is to place ments requires appreciation of the anatomy and physiology of eye move- and maintain an object of visual interest on each fovea simultaneously ment control. Normal vision is accomplished by a continuous cycle of to allow visualization of a single, stable object. To meet this goal, sev- visual fixation and visual analysis, interrupted by rapid gaze-shifting eye eral types, or functional classes, of eye movements exist, including movements called saccades. Subjects with intact afferent visual systems are saccades, smooth pursuit, vestibular reflexes, optokinetic nystagmus capable of discerning small details comparable to a Snellen acuity of 20/13 (OKN), and vergence. Anatomically and physiologically, separate provided that the target image is maintained within 0.5 degree of the fovea supranuclear (i.e., prenuclear) neuronal networks coordinate their centralis. However, 10 degrees from fixation, the resolving power of the activity to initiate and modulate each type of eye movement. retina drops to 20/200. Although the peripheral retina has poor spatial res- olution, it is exquisitely sensitive to movement (temporal resolution). The Saccades image of an object entering the peripheral visual field stimulates the retina The saccadic system moves the eyes rapidly (up to 800 degrees/sec) and to signal the ocular motor system to make a saccade to fixate the image on conjugately to fixate new targets (Fig. 18.2, A). Saccades may be generated the fovea. Visual information concerning spatial resolution (fine detail) voluntarily or in response to verbal commands in the absence of a visible and color travels via retinal ganglion (P) cells to the parvocellular layers target. Reflexive saccades occur in response to peripheral retinal stimuli of the lateral geniculate nucleus (LGN), whereas information concerning such as visual threat or to sounds. Also, saccades create the fast com- temporal resolution (movement) travels via retinal ganglion (M) cells to ponents of nystagmus, including OKN. In general, voluntary saccades 201 #*" #
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202 PART I Common Neurological Problems PFC BSG FEF SC SEF SN CN Thalamus Dorsal stream MT PPC Striate LGN cortex: Ventral stream Area 17 ESC ESC Posterior V2 V4 temp area A SEF PFC FEF PPC 7a PEF LIP MST PTO MT SC Area 17 PPRF B Fig. 18.1 A, Overview of the combined afferent and efferent visual system. B, Areas in the human brain that are believed to be important in generating saccades and pursuit. BSG, Brainstem saccadic generator; CN, caudate nucleus; ESC, extrastriate cortex; FEF, frontal eye field; LGN, lateral geniculate nucleus; LIP, lateral intraparietal area; MST, medial superior temporovisual area; MT, middle temporovisual area; PEF, parietal eye field; PFC, prefrontal cortex; PPC, posterior parietal cortex area; PPRF, paramedian pontine reticular formation; PTO, parietotemporo-occipital junction; SC, superior colliculus; SEF, supplementary eye field in the supplementary motor area; SN, substantia nigra; 7a, area 7a. (A, Redrawn from Stuphorn, V., Schall, J.D., 2002. Neuronal control and monitoring of the initiation of movements. Muscle Nerve 26, 326–339.) are generated in the contralateral frontal cortex and reflexive saccades area 46); the vestibular cortex in the posterior superior temporal gyrus; in the contralateral parietal cortex. More specifically, several specialized and the hippocampus in the medial temporal lobe. Collectively, these areas in the cortex—identified by pathological lesions, transcranial mag- cortical areas and the superior colliculus are parts of a network that netic stimulation, and neurophysiological studies (particularly in mon- determines when different types of saccades occur and where they go: keys)—play a major role in controlling saccades (see Fig. 18.1, B). These that is, they calculate their direction and amplitude (accuracy). include the FEFs in the precentral gyrus and sulcus (Brodmann area 6 To enable the small, strap-like extraocular muscles to move the in humans); the supplementary eye fields (SEFs) on the dorsomedial relatively large globes and overcome inertia and elastic recoil of the aspect of the superior frontal gyrus anterior to the supplementary motor viscous orbital contents, the yoked agonist muscles for a conjugate area; the parietal eye fields (PEFs) in the lateral intraparietal (LIP) area saccade require a burst of innervation (called the pulse) to occur in monkeys which is equivalent to an area in the intraparietal sulcus near simultaneously with reciprocal inhibition of yoked antagonist muscles the angular gyrus region (Brodmann areas 39 and 40 in humans); the (Robinson, 1970) (Fig. 18.3, A). The saccadic pulse is generated by posterior parietal cortex (PPC) (Brodmann area 39 in the upper angular excitatory burst neurons (EBNs) in the brainstem: for horizontal sac- gyrus in humans); the dorsolateral prefrontal cortex (PFC) (Brodmann cades, EBNs are located in the ipsilateral paramedian pontine reticular #*" #
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 CHAPTER 18 Neuro-Ophthalmology: Ocular Motor System 203 +20° Pulse Step 200 msec 10° 0° + + Target LLR -20° LMR Stimulus Eye Braking A saccade Eye Pulse Pulse-step Step A EBN NI B Motor neuron Target Eye P B dt C Neural integrator B Fig. 18.3 Ocular Motor Events for a Leftward Saccade. A, After Fig. 18.2 Simulated Eye Movement Recordings. By convention for the appearance of a stimulus 20 degrees to the left of fixation (−20 horizontal movements, upward deflections represent rightward eye degrees), the eyes move to the target with a saccade after a latency of movements and downward deflections represent leftward eye move- 200 msec. Idealized electromyography of the left extraocular muscles ments. A, Saccades. A target moves rapidly 10 degrees to the right. shows the activity of the agonist (the left lateral rectus [LLR]) and the After a latency of about 200 msec, the eye follows with a fast sac- antagonist (the left medial rectus [LMR]) muscles. B, The pulse origi- cade to target. When the target returns to the center, the sequence nates in the excitatory burst neurons (EBNs) and is mathematically inte- is repeated in the opposite direction. B, Pursuit. The target moves in grated by the neural integrator (NI); both signals are added to produce a sinusoidal pattern in front of the patient. The eye follows the target the pulse-step of the innervation to the ocular motor neurons. C, The after a latency of about 120 msec, but pursuit movements to the right pause cells (P) discharge continuously, suppressing the burst cells (B), are defective, resulting in the rightward “cogwheel” (saccadic) pursuit. except during a saccade, when they “pause,” allowing the burst cells to Pursuit to the left is normal. discharge and generate a pulse. (Reprinted with permission from Lavin, P.J.M., 1985. Conjugate and disconjugate eye movements. In: Walsh, T.J. [Ed.], Neuro-ophthalmology: Clinical Signs and Symptoms. Lea & formation (PPRF) just rostral to the abducens nucleus (Horn et al., Febiger, Philadelphia.) 1995); for vertical and torsional saccades, EBNs are located in the rostral interstitial medial longitudinal fasciculus (RIMLF) in the mid- brain (Horn and Büttner-Ennever, 1998). Whereas EBNs discharge Typically, saccades are assessed clinically by asking the subject to to generate the pulse, inhibitory burst neurons (IBNs) discharge to make rapid eye movements between two stationary visual targets in inhibit the yoked antagonist muscles (Strassman et al.,1986; Scudder the horizontal and then vertical planes. The examiner should observe et al., 1988). for abnormalities of saccade onset, speed, conjugacy, accuracy, and At saccade end, maintenance of the eyes on target in an eccentric trajectory. position requires transition of the pulse command into a new lower-level tonic step command provided by neural integrators (NIs) (see Fig. 18.3, Smooth Pursuit B). The NIs for horizontal eye movements include the medial vestibular The pursuit system enables the eyes to track slowly moving targets nucleus and nucleus prepositus hypoglossi (Langer et al., 1986), whereas (up to 70 degrees/sec) to maintain the image stable on the fovea. vertical integration occurs in the interstitial nucleus of Cajal (INC). The Specially trained subjects (e.g., baseball players) are capable of cerebellum and EBNs maintain the output of the NIs by controlling smooth-pursuit eye movements as fast as 100 degrees/sec. Control gain, via a positive feedback loop, to keep the eyes on target. of smooth-pursuit eye movements is complex (see Fig. 18.1) but Just before and during saccades, EBNs are inhibited tonically by essentially consists of three components: sensory, motor, and atten- omnipause neurons (OPNs) located in the nucleus raphe interpositus tional-spatial. The stimulus for pursuit is movement of an image (RIP) in the caudal pons (Büttner-Ennever et al., 1988). Thus, OPNs— across the fovea at velocities greater than 3 to 5 degrees/sec. The which receive input from the cerebrum, cerebellum, and superior col- sensory component includes the striate cortex (area 17), which liculus—allow a saccade when they cease discharging and permit EBNs receives information from the retinal ganglion (M) cells via the to fire (see Figs. 18.3, C and 18.4). For example, for a leftward saccade, magnocellular layer of the LGN and the optic radiations. The stri- OPNs cease discharging, the left lateral rectus and the right medial rec- ate cortex projects to the prestriate cortex (parieto-occipital areas tus muscles receive a pulse of innervation to generate the saccade, and 18 and 19) and then to the superior temporal sulcus region, which their antagonists, the left medial and right lateral rectus muscles, are contains cortical areas MT and MST in monkeys, equivalent to the reciprocally inhibited. Upon reaching the visual target, the pulse com- PTO junction in humans. This sensory subsystem encodes for loca- mand, mediated by the NIs, transitions to tonic step command to hold tion, direction, and velocity of objects moving in the contralateral the eyes in place. The saccade has ended and OPNs resume firing. visual field and is the major afferent input driving smooth pursuit. #*" #
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204 PART I Common Neurological Problems P Pontine nuclei B Flocculus T Vermis Lobules VI, VII Oc MVN VI Fig. 18.5 Postulated double decussation of pursuit pathways in the brainstem and cerebellum. The first decussation consists of excitatory E mossy fiber projections from the pontine nuclei to granule cells, which Fig. 18.4 Electrophysiological Events During a Saccade. P rep- excite basket cells and stellate cells in the contralateral cerebellar resents an intraneuronal recording from a pause cell and demonstrates flocculus. The basket and stellate cells inhibit Purkinje cells, which in a constant discharge, which ceases just before and during a saccade, turn inhibit neurons in the medial vestibular nucleus (MVN). The sec- allowing an excitatory burst neuron (B) to discharge during the saccade ond decussation consists of excitatory projections from the MVN to pulse. T represents the discharge in a tonic neuron, which increases the opposite abducens nucleus (VI). (Reprinted with permission from after the pulse as a result of integration of the pulse to a step. Both the Johnston, J.L., Sharpe, J.A., Morrow, M.J., 1992. Paresis of contralat- pulse (P) and the tonic output (T) of burst-tonic neurons innervate the eral smooth pursuit and normal vestibular smooth eye movements after ocular motor neurons (Oc). The result is a rapid contraction of the extra- unilateral brainstem lesions. Ann Neurol 31, 495–502.) ocular muscle, which moves the eye from primary position and holds it in an eccentric position (E). Pursuit defects fall into four categories: 1. Retinotopic defects: Lesions of the geniculostriate pathway cause It projects to the pursuit motor subsystem bilaterally, also located in impaired pursuit in both directions in the contralateral visual field the PTO region, as well as to frontal and SEFs. This pursuit pathway defect. Defects also occur with lesions of areas MST or MT; these is indirect and focuses attention on small moving targets. A direct patients have apparently normal visual fields but selective “blind- pathway bypassing the attentional-spatial subsystem enables large ness” for movement. moving objects, such as full-field optokinetic stimuli, to generate 2. Impaired pursuit, worse in the ipsilateral direction in both hemi- smooth pursuit contralaterally even when the subject is inattentive. fields, occurs with lesions in the lateral aspect of area MST and the The superior colliculus also contributes to pursuit drive. The PTO foveal representation of area MT in monkeys, similar to a focal projects to the ipsilateral dorsolateral and lateral pontine nuclei. PTO lesion in humans. Lesions in the FEF, posterior thalamus, To control ipsilateral tracking, pursuit pathways undergo a double midbrain, ipsilateral pons, contralateral cerebellum, contralateral decussation from the pontine nuclei to the contralateral cerebellar pontomedullary junction, and ipsilateral abducens nucleus can also flocculus and medial vestibular nucleus and then back to the ipsilat- impair pursuit in both hemifields but more markedly in the ipsilat- eral abducens nucleus (Fig. 18.5). eral direction. Clinically, smooth pursuit is assessed by having the subject follow 3. Symmetrically impaired pursuit in both horizontal directions a very slowly moving visual target in the horizontal and then vertical occurs with focal lesions in the parieto-occipital region (area 39), planes while the examiner observes for any corrective saccades super- medication (e.g., anticonvulsants, sedatives, and psychotropic imposed upon pursuit. If the target moves too quickly or changes agents), alcohol, fatigue, inattention, schizophrenia, encephalopa- direction abruptly, even in healthy individuals, or if the pursuit system thy, a variety of neurodegenerative disorders, and age (infants and is impaired, the eyes become unable to maintain pace with the target the elderly). and fall behind. Consequently the image moves off the fovea, produc- 4. An acute nondominant (e.g., parietal, frontal) hemispheric lesion ing a retinal error signal that provokes a corrective (catch-up) saccade associated with a hemispatial neglect syndrome causes transient and again fixates the target. Then the cycle repeats itself, resulting in loss of pursuit beyond the midline into contralateral hemispace. saccadic (“cogwheel”) pursuit (see Fig. 18.2, B). Bidirectional defective pursuit eye movements, a normal finding in infants, are nonspecific Vestibular Eye Movements and occur under conditions of stress or fatigue or with sedative medi- The vestibular eye movement system maintains a stable image on the cation. However, impaired tracking in one direction suggests a struc- retina during head movements. The semicircular canals respond to tural lesion of the ipsilateral pursuit system (see Fig. 18.2, B). rotational acceleration of the head by driving the vestibulo-ocular reflex #*" #
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 CHAPTER 18 Neuro-Ophthalmology: Ocular Motor System 205 Gaze left movements, to stabilize images on the retina in situations such as large turns or spinning. When the eyes reach their limit of movement in the orbits, a reflexive saccade allows refixation to a point further forward LE CN III RE in the direction of head rotation. The sequence repeats itself, resulting in OKN, comprising slow following pursuit-like movements and rapid 3 3 saccadic resetting quick phases. In humans, the optokinetic system predominantly responds to fix- MLF ation and pursuit of a moving target (immediate component) and to 6 6 a lesser extent velocity storage (delayed component), which involves + – neural circuitry in the vestibular system. Velocity storage is a mech- CN VI PPRF anism by which the central nervous system (CNS), predominantly Ampulla the vestibular system including the vestibulocerebellum, prolongs or + + causes perseveration of short signals generated by the vestibular end Horizontal organ to enhance orientation in space. Velocity storage is largely invol- semicircular canal untary. Probably, the optokinetic system evolved to supplement the VN vestibular system during sustained rotations. True OKN is a rhythmic involuntary conjugate ocular oscillation Fig. 18.6 A lateral head turn (yaw, or side to side) induces movement provoked by a compelling full visual field stimulus, such as that pro- of the endolymph in the ipsilateral horizontal semicircular canal toward duced by rotating an image of the environment around the patient or the ampulla (as would warm water caloric stimulation of the external by turning the patient in a revolving chair. Elicitation of OKN using a auditory meatus/tympanic membrane) and thus excites the contralat- pocket tape is a useful bedside test but evaluates only foveal pursuit and eral abducens nucleus and inhibits the ipsilateral abducens nucleus via the vestibular nuclei (VN). Each abducens nucleus innervates the ipsi- refixation saccades, which is helpful in several circumstances, as pointed lateral lateral rectus muscle via the abducens nerve and the contralat- out in respective sections further on. The subject is asked to directly look eral medial rectus muscle via the abducens nucleus interneurons, the at the stimulus without following the motion. The examiner should note medial longitudinal fasciculus (MLF), and the neurons for the medial rec- the presence or absence of slow and quick phases of eye movement in tus (part of cranial nerve [CN] III nucleus). Neurons in each paramedian response to stimulus motion. OKN is a very reflexive eye movement that pontine reticular formation (PPRF) also have an excitatory input to the cannot actively be suppressed while attending to the stimulus. ipsilateral abducens nucleus and an inhibitory input to the contralateral abducens nucleus for saccades and quick phases of nystagmus. LE, Vergence Left eye; RE, right eye. (Adapted from Lavin, P.J.M., 1985. Conjugate In humans and other frontal-eyed animals capable of binocular and disconjugate eye movements. In: Walsh, T.J. [Ed.], Neuro-ophthal- fusional vision, disconjugate (vergence) eye movements are neces- mology: Clinical Signs and Symptoms. Lea & Febiger, Philadelphia.) sary to maintain ocular alignment on an approaching or retreating object (convergence and divergence, respectively). Vergence move- (VOR) to maintain the eyes in the same direction in space during head ments are essential for binocular single vision and stereoscopic depth movements. The otoliths (utricle and saccule) are gravity receptors that perception. Electromyography demonstrates that divergence is an respond to linear acceleration and static head tilt (gravity)—that is, with active movement (Tamler and Jampolsky, 1967), although it is not ocular counter-rolling. The vestibular system stabilizes the direction of as dynamic or as much under voluntary control as convergence. The gaze during head movements by virtue of changes in its tonic input to principal driving stimuli for vergence movements, relayed from the the ocular motor nuclei. This is illustrated most clearly by the horizon- occipital cortex, are accommodative retinal blur (unfocused vision) tal VOR (Fig. 18.6). Each horizontal semicircular canal innervates the and fusional disparity (diplopia). Each of these stimuli can operate ipsilateral medial vestibular nucleus to inhibit the ipsilateral abducens independently. Convergence occurs predominantly via activation of nucleus and excite the contralateral abducens nucleus. The ampulla of the medial rectus muscles, though each eye also excyclotorts (more the right horizontal semicircular canal is stimulated by turning the head so in downgaze) to facilitate stereoscopic perception (Brodsky, to the right (or by warm caloric stimulation). This mechanical infor- 2002). In addition, the pupils change size as part of the near reflex mation is transduced by the vestibular end organ to electrical signals to increase the depth of field and sharpen the focus of the optical and transmitted to the ipsilateral vestibular nucleus. Excitatory infor- system. mation is then relayed to the contralateral abducens nucleus and inhibi- Although the source of adduction commands for versional horizon- tory information to the ipsilateral abducens nucleus, causing the eyes to tal eye movements originates in the abducens nucleus, signals for con- deviate in the direction opposite to head rotation, thus maintaining the vergence-mediated adduction do not arise here (Gamlin et al., 1989; direction of gaze. The vestibular system is discussed further in Chapter Gamlin and Mays, 1992). Although the precise locations of the conver- 22. gence and divergence centers are unknown, important areas include Vestibular eye movements are assessed most readily on clinical the rostral superior colliculus, the mesencephalic reticular formation examination by testing visually enhanced oculocephalic reflexes in (MRF) dorsolateral to the oculomotor nucleus, and the supraoculo- horizontal and vertical directions. The subject is asked to maintain fix- motor area above the oculomotor nucleus; further, separate pathways ation on a visual target as the examiner actively rotates the head in the controlling fast (saccade-like) and slow convergence also exist (Bohlen horizontal and vertical directions while noting the range of excursions et al., 2016, 2017; Cohen and Büttner-Ennever, 1984; May, et al., 2016, of the eyes and the smoothness of the eye movement. 2018; Rucker et al., 2019; Van Horn et al., 2013). Clinically, vergence is tested by asking the subject to either follow Optokinetic Nystagmus a slowly moving target as it moves toward and away from him or her The optokinetic system uses visual reference points in the environ- on a midline horizontal plane extending centrally toward the examiner ment to maintain orientation. It complements the vestibulo-ocular between the subject’s eyes (slow vergence) or to make rapid jumps of system, which becomes less responsive during slow or sustained head the eyes between near and distant midline visual targets (fast vergence). #*" #
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206 PART I Common Neurological Problems TABLE 18.1 Actions of Extraocular Muscles Muscle plane 90° Muscle Primary Secondary Tertiary y 23° Medial rectus Adduction 67° Lateral rectus Abduction Axis of Superior rectus Elevation Intorsion Adduction rotation Inferior rectus Depression Extorsion Adduction Superior oblique Intorsion Depression Abduction Inferior oblique Extorsion Elevation Abduction x TABLE 18.2 Yoked Muscle Pairs Ipsilateral Contralateral Medial rectus Lateral rectus Superior rectus Inferior oblique 90° Inferior rectus Superior oblique Axis of A y rotation 51° 39° Superior oblique Superior rectus Medius rectus x Inferior rectus Muscle plane B Fig. 18.8 A, Relationship of the muscle plane of the vertical rectus Lateral rectus muscles to x- and y-axes. B, Relationship of the muscle plane of the oblique muscles to the x- and y-axes. (Reprinted with permission from Inferior oblique Von Noorden, G.K., 1985. Burian-Von Noorden’s Binocular Vision and Ocular Motility, third ed. Mosby, St. Louis.) Fig. 18.7 The Six Extraocular Muscles for Each Eye. inhibited (the Sherrington law of reciprocal inhibition), thereby allow- The Final Common Pathway of Eye Movements ing the eyes to move conjugately and with great precision. The pull- The supranuclear networks send command signals to a “final common ing actions of the extraocular muscles evolved to move the eyes in the pathway” that includes the ocular motoneuron, neuromuscular junc- planes of the semicircular canals, which are not strictly horizontal or tion, and the final effector organ of eye movements—the extraocular vertical. These pulling actions are influenced by both the conventional muscle. For some time it was believed that all motoneurons and extra- insertions of the global layer of each extraocular muscle directly into the ocular muscle fibers participate fully in all types of eye movements eyeball and by the insertion of the orbital layer into the fibromuscular (Scott and Collins, 1973); however, more recently it was shown that connective tissue sheath that envelopes each rectus muscle (Fig. 18.9). specific neuronal and muscle fiber types may be more important for This arrangement forms a pulley system that is innervated actively certain types of eye movements. (Demer, 2002), stabilizes rotation of the globes in three-dimensional Each eye receives input from three ocular motor cranial nerves: space during complex eye movements (e.g., when a horizontal muscle oculomotor or cranial nerve III, trochlear or cranial nerve IV, and contracts during upgaze), and prevents excessive retraction of the globe abducens or cranial nerve VI. (See Chapter 103 for a review of the anat- within the orbit during extraocular muscle contraction. Techniques for omy of each ocular motor cranial nerve.) The six extraocular muscles examining the final common pathway are discussed further on. (Table 18.1) of each eye are yoked in pairs (Table 18.2), so that the eyes move conjugately (versions) to maintain alignment of the visual DISORDERS OF EYE MOVEMENTS— axes (Fig. 18.7). The actions of the medial and lateral recti are confined to the horizontal plane. The actions of the superior and inferior recti OPHTHALMOPLEGIA AND OCULAR are solely vertical when the eye is abducted 23 degrees. The oblique MISALIGNMENT muscles, the main cyclotorters, also act as pure vertical movers when the eye is adducted 51 degrees (Fig. 18.8). For practical purposes, the Approach to History and Examination vertical actions may be tested at 30 degrees of adduction and abduc- History tion. According to the Hering law of dual innervation, yoked muscles The most common symptom with disorders of ocular misalignment, receive equal and simultaneous innervation while their antagonists are with or without ophthalmoplegia (i.e., reduced range of movement of #*" #
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 CHAPTER 18 Neuro-Ophthalmology: Ocular Motor System 207 Pulley sling Elastin Collagen Trochlea Pulley ring Global Pulley layer Smooth ring muscle Orbital layer IO Orbital layer SR SO MR LR Pulley sling IR IO Fig. 18.9 Diagrammatic representation of the structure of orbital connective tissues and their relationship to the fiber layers of the rectus extraocular muscles. Coronal views are represented at levels indicated by the arrows in horizontal section. IO, Inferior oblique; IR, inferior rectus; LR, lateral rectus; MR, medial rectus; SO, superior oblique; SR, superior rectus. (Redrawn from Demer, J.L., 2002. The orbital pulley system: a revolution in concepts of orbital anatomy. Ann N Y Acad Sci 956, 17–32.) one or both eyes), is diplopia (double vision). Diplopia is encountered misalignment. Theoretically, the onset of double vision should be frequently in neurological practice and may reflect an emergency with abrupt. However, in practice, the history of onset may be vague due high morbidity and mortality or a benign acquired or lifelong condi- to misinterpretation as blurring, intermittent occurrence, small tion. Box 18.1 gives for a summary of the general approach to diplo- amplitude, or compensation by head position. Occasionally visual pia. The first question (and exam technique, if the patient is uncertain) confusion occurs because each fovea fixates a different object simul- is to assess if the diplopia is monocular (fails to resolve by covering taneously, causing the perception of two objects in the same place each eye) or binocular (resolves with covering each eye). Most often at the same time (Fig. 18.12). Patients may misinterpret physiolog- monocular diplopia is due to refractive error or dry eye, which is con- ical diplopia, a normal phenomenon, as a pathological symptom. firmed if double revolves when the patient looks through a pinhole Physiological diplopia occurs when a subject fixates an object in the or some other ocular cause (Box 18.2). An exception to the “rule” foreground and then becomes aware of another object farther away that intraocular pathology causes monocular diplopia may occur if a but in the direction of gaze. The nonfixated object is seen by non- retinal distortion such as an epiretinal membrane displaces the fovea corresponding parts of each retina and is perceived by the mind’s to an extrafoveal location; thus, an intraocular process results in bin- (cyclopean) eye as double (Fig. 18.13). ocular diplopia (Verveka et al., 2017). This is the “dragged-foveal dip- Box 18.1 gives additional historical elements and examination lopia syndrome” and likely results from rivalry between central and techniques for diplopia. Horizontal diplopia is caused by impaired peripheral fusional mechanisms (Guyton, 2018). Anisoconia (ani- abduction or adduction of an eye and vertical, by impaired elevation seikonia), defined as a difference of 20% or more between the image or depression. Diplopia that is worse in one particular direction of size from each eye and usually due to an optical aberration caused gaze suggests that motility in that direction is impaired. Diplopia that by anisometropia or cataract surgery, can cause diplopia, which may is worse at distance usually accompanies impaired abduction or diver- resolve with complex optical correction. Small differences in image gence, whereas worsening at near accompanies impaired adduction or size, even less than 3%, can cause visual discomfort or asthenopia convergence. For example, lateral rectus muscle weakness causes hor- without frank diplopia. izontal diplopia worse at distance and on looking to the side of the Images of the same object must fall on corresponding points of weak muscle. Medial rectus weakness causes horizontal diplopia that each retina to maintain binocular single vision (fusion) and stere- is worse at near and to the contralateral side. Care should be taken not opsis (Fig. 18.10). If the visual axes are not aligned, the object is seen to localize too early, as a suspected lateral rectus weakness by history by noncorresponding (disparate) points of each retina and diplo- could turn out to be due to myasthenia or a restrictive process in the pia results (Fig. 18.11). Also, it is helpful to remember that patients orbit that affects the medial rectus (Box 18.3). Isolated vertical diplo- with poor vision in one eye may not experience diplopia and that pia (Box 18.4) is commonly caused by superior oblique weakness. If binocular visual blurring (visual blur that resolves completely acquired, one image is usually tilted—an infrequent finding when the with each eye covered) or vague “eye strain” may represent ocular condition is congenital. #*" #
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208 PART I Common Neurological Problems BOX 18.1 Assessment of the Patient with Diplopia History Versions (pursuit, saccades, and muscle overaction) Monocular or binocular? Convergence (does miosis occur?) Horizontal, vertical, or oblique separation of the images? Ductions Effect of distance of target (worse at near or far)? Ocular alignment (muscle balance) in the “forced primary position” and comi- Effect of fatigue? Worse in morning or evening? tance pattern Transient or persistent? If transient, effect of gaze direction or truly transient Pupils (consider giant cell arteritis)? Lids (examine palpebral fissures, levator function, fatigue) Tilting of one image? Vestibulo-ocular reflexes (doll’s eye reflex) Is there is a history of head trauma, cancer, “lazy eye,” eye surgery, or botuli- Bell phenomenon num toxin? Prism measurements What other symptoms are present (i.e., headache, eye pain, dizziness, weak- Stereopsis (Titmus stereo test) ness)? Optokinetic nystagmus Observation General Neurological Examination Head tilt or turn? (“FAT* scan”) Other Tests Where Indicated Ptosis (fatigue)? Listen for bruits Pupil size? Anisocoria? Forced ductions Proptosis? Edrophonium (Tensilon) test Lights on-off test for the dragged-fovea diplopia syndrome Eye Examination Ice-pack test for ptosis Visual acuity (each eye separately, and binocularly if primary position nystag- mus present) * FAT, Family album tomography—review of old photographs for head tilt, pupil size, lids, ocular alignment, etc. For magnification, use an ophthal- moscope, magnifying glass, or slit lamp. BOX 18.2 Causes of Monocular Diplopia pattern of alignment. A “hetero” pattern indicates a misalignment. Two different terms are used, heterotropia or heterophoria, depending Uncorrected refractive error on whether binocular fusion must be disrupted for misalignment to Equipment failure (defective contact lens, ill-fitting bifocals in patients with be detected. With a tropia, there is a manifest deviation of one eye that dementia) can be readily seen. With a phoria, disruption of binocular fusion must Corneal disease (e.g., astigmatism, dry eye, keratoconus) occur to detect an ocular misalignment. Many individuals have a latent After surgery for long-standing tropia (eccentric fixation) horizontal heterophoria, which may become manifest (heterotropia) Corrected long-standing tropia (eccentric fixation) under conditions of stress such as fatigue, exposure to bright sunlight, Foreign body in aqueous or vitreous media or ingestion of alcohol, anticonvulsants, or sedatives. Divergent eyes Iris abnormalities (polycoria, trauma) are said to be exotropic and convergent eyes esotropic. With vertical Lens: multirefractile (combined cortical and nuclear) cataracts, subluxation misalignment, when the nonfixating eye is higher, the patient is said Occipital cortex (bilateral monocular): migraine, epilepsy, stroke, tumor, to have a hypertropia, and when it is lower, a hypotropia—although by trauma (palinopsia, polyopia) convention, right or left hypertropia is more often used than the term Psychogenic hypotropia. Retinal disease (rare) Techniques to assess ocular alignment. Examination of ocular alignment should be performed for binocular diplopia. The alignment pattern of the eyes in primary position should be assessed first. Examination Horizontal diplopia is accompanied by either an eso- or exo- deviation. To evaluate disorders causing ocular misalignment with or without Vertical diplopia is accompanied by either a left or right hyper- ophthalmoplegia, first note any abnormal resting head turn or tilt deviation. With diplopia from paralytic strabismus, the image from and then determine the range of versions (Fig. 18.14, A) (conjugate the nonfixating paretic eye is the false image and is displaced in the eye movements) and ductions. Ductions involve the range of motion direction of action of the weak muscle. Thus, a patient with esotropia monocularly (see Fig. 18.14, B). If ductions are not full, restrictive has uncrossed diplopia (see Fig. 18.11, A) and a patient with exotropia limitation should be assessed by moving the eye forcibly (see the sec- has crossed diplopia (see Fig. 18.11, B). After a variable period, a patient tion titled “Forced Ductions,” further on). If a conjugate defect (i.e., may learn to ignore or suppress the false image. If suppression occurs gaze palsy of both eyes to movement in the same direction) is present, before visual maturity (approximately 6 years of age) and persists, determine whether the eyes move reflexively (i.e., whether the range central connections in the afferent visual system fail to develop fully, limitation can be overcome) by testing for the oculocephalic reflex leading to permanent visual impairment in the deviated nonfixating and the Bell phenomenon (spontaneous deviation of the eyes, usually eye (developmental amblyopia). Amblyopia is more likely to develop upward, with eye closure). Causes of gaze palsies and ophthalmoplegia with esotropia than with exotropia because exotropia is commonly are outlined in Table 18.3 and discussed in the following paragraphs. intermittent. After visual maturity, suppression and amblyopia do not Heterophorias versus heterotropias. When no ocular occur; instead, the patient may learn to avoid diplopia by ignoring the misalignment of the eyes is present, the patient is said to have an “ortho” false image. #*" #
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 CHAPTER 18 Neuro-Ophthalmology: Ocular Motor System 209 Before determining ocular alignment, the examiner must neutral- AB ize a head tilt or turn by placing the head in the “controlled (forced) primary position”; otherwise, misalignment may go undetected because of the compensating head posture. Subjective tests of ocular alignment include the red glass, Maddox rod, Lancaster red-green, and Hess screen tests. With the red glass test, the patient views a penlight while a red filter or glass is placed, by convention, over the right eye. This allows easier A B identification of the image seen by each eye; the right eye views a red light and the left a white light. The addition of a green filter over the left eye, using red-green glasses, further simplifies the test for younger or less reliable individuals. The target light is shown in the nine diagnostic positions of gaze (see Fig. 18.14, A). As the light moves into the field of action of a paretic muscle, the images separate. The individual is asked to signify where the images are most widely separated and to describe their relative positions. Interpretation of the results is summarized in f1 f2 Fig. 18.15. The Maddox rod test uses the same principle as the red glass test, but the images are completely dissociated. A point of light seen through the rod, which is a series of half cylinders, is changed to a straight line AB that is seen perpendicular to the cylinders (Fig. 18.16). This dissocia- tion of images (a point of light and a line) breaks fusion, enabling the detection of heterophorias as well as heterotropias. Cyclotorsion may be detected by asking if the image of the line is tilted (Fig. 18.17). The Maddox rod can be positioned to produce a horizontal, vertical, or Mind’s eye oblique line. Similar tests include the Lancaster red-green test and the Hess screen test, which use the same principles, although they are unlikely to be used Fig. 18.10 Each eye views the target, AB, from a different angle. The by a neurologist. Each eye views a different target (a red light through fovea of the left eye (f1) views the “A” side of the target and the fovea the red filter and a green light through the green filter). The relative posi- of the right eye (f2) views the “B” side of the target. The occipital cor- tions of the targets are plotted on a grid screen and analyzed to identify tex—the cyclopean (mind’s) eye—integrates the disparate images so the paretic muscle. These haploscopic tests are used mainly by ophthal- that a three-dimensional image (AB) of the target is perceived. This phe- mologists to quantitatively follow patients with motility disorders. nomenon is called sensory fusion. The Hirschberg test, an objective method of determining ocular deviation in young or uncooperative patients, is performed by observ- ing the point of reflection of a penlight held approximately 30 cm from the eyes (Fig. 18.18). The light should be centered on the cornea in False False Object image image Object f f f f LLR LMR RMR RLR LLR LMR RMR RLR A (paretic) B (paretic) Fig. 18.11 Misalignment of the Visual Axes. A, Esotropia caused by a right lateral rectus (RLR) palsy results in the right eye turning inward so that the image falls on the retina, nasal to the fovea (f), and is pro- jected by the mind’s eye to the temporal field. That is, the false image is projected in the direction of action of the paretic muscle, causing uncrossed (homonymous) diplopia. B, Exotropia caused by a paretic right medial rectus (RMR) muscle results in the image falling on the retina temporal to the fovea, with projection to the nasal field in the direction of the action of the paretic RMR, causing crossed (heteronymous) diplopia. LLR, Left lateral rectus; LMR, left medial rectus. #*" #
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210 PART I Common Neurological Problems O X f f f f O X Mind’s eye Fig. 18.12 Visual Confusion (a rare occurrence). Each fovea (f) views a different object, which is projected to the visual cortex by the cyclo- Fig. 18.13 Physiological Diplopia. The cyclopean eye views the pean (mind’s) eye and perceived in the same place at the same time. object (the square) as a single object because each fovea (f) fixates it. The images of a nonfixated target (the circle) fall on noncorresponding one eye; if it is not also seen in the center of the other eye, an ocular points of each retina, so the object appears double. misalignment is likely to be present. One millimeter of decentration is equal to 7 degrees of ocular deviation. One degree is equal to approx- covered eye is uncovered, it refixates by moving back; the uncovered imately 2 prism diopters. One prism diopter is the power required to eye is immediately covered and loses fixation. The cross-cover test pre- deviate (diffract) a ray of light by 1 cm at a distance of 1 m (Fig. 18.19). vents binocular viewing, and thus foveal fusion, by always keeping one The cover-uncover test is determined for both distance (tested at 6 eye covered. Many normal subjects without a history of diplopia are m) and near (tested at 33 cm) vision. The patient is asked to fixate exophoric because of the natural alignment of the orbits. an object at the appropriate distance. The left eye is covered while the Fixation switch diplopia occurs in patients with long-standing patient maintains fixation on the object. If the right eye is fixating, strabismus who partially lose visual acuity in the fixating eye, usu- it remains on target, but if the left eye alone is fixating, the right eye ally because of a cataract or refractive error (Pineles, 2016). Such moves onto the object. If the uncovered right eye moves in (adducts), patients avoid double vision usually by ignoring the false image from the patient has a right exotropia; if it moves out (abducts), the patient the nonfixating eye, but a significant decrease in acuity in the “good” has an esotropia; if it moves down, a right hypertropia; if it moves up, eye forces them to fixate with the weak eye. This causes misalignment a right hypotropia (otherwise called a left hypertropia). The physician of the previously good eye and results in diplopia. Fixation switch should always observe the uncovered eye. The test should be repeated diplopia can usually be treated successfully with appropriate optical by covering the other eye. Prisms are used—mainly by neuro-oph- management. thalmologists, ophthalmologists, orthoptists, and optometrists—to Comitance versus incomitance. If a patient has an ocular measure the degree of any ocular deviation (see Fig. 18.19). If dip- misalignment (tropia or phoria), the physician must determine lopia is due to breakdown of a long-standing (congenital) deviation, whether it is comitant or incomitant (i.e., noncomitant) by checking prism measurement can also be used to detect supranormal fusional the degree of deviation in the nine diagnostic cardinal positions amplitudes (large fusional reserves) to help confirm the long-standing of gaze (see Fig. 18.14, A). When the pattern and degree of ocular nature. If no manifest deviation of the visual axes is found using the misalignment—that is, the angle of deviation of the visual axes— cover-uncover test, the patient is orthotropic. Then the physician may is constant regardless of the direction of gaze, the patient has a perform the cross-cover test. comitant strabismus (heterotropia). For example, if a patient has an During the cross-cover test (alternate-cover test), the patient is asked esotropia in primary position that does not change (and the degree to fixate an object, and then one eye is covered for at least 4 seconds of diplopia does not change) in right and left gaze compared with before the second eye is covered. The examiner should observe the primary position, the misalignment is comitant. When the degree of uncovered eye. If the patient is orthotropic, the uncovered eye does misalignment varies with gaze direction, the patient has an incomitant not move but the covered eye loses fixation and assumes its position of (paralytic due to a weak eye muscle or restrictive due to a stiff eye rest—latent deviation (heterophoria or phoria). In that case, when the muscle in the orbit) strabismus. #*" #
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 CHAPTER 18 Neuro-Ophthalmology: Ocular Motor System 211 BOX 18.3 Causes of Esotropia BOX 18.4 Causes of Vertical Diplopia Abducens palsy (unilateral or bilateral) Common Causes Abducens palsy with contracture of antagonist (ipsilateral medial rectus) Superior oblique palsy during recovery Thyroid eye disease (muscle infiltration) Accommodative esotropia Myasthenia gravis Acute thalamic esotropia Skew deviation (brainstem, cerebellar, hydrocephalus) Chiari malformation (via abducens palsy or increased convergence tone due to cerebellar dysfunction) Less Common Causes Congenital esotropia (also acquired, cyclic) Orbital inflammation (myositis, idiopathic orbital inflammatory syndrome Cyclical oculomotor palsy (spastic phase) [previously designated “orbital pseudotumor”]) Divergence insufficiency or paralysis Orbital infiltration (lymphoma, metastases, amyloid, IgG-4–related disease) Duane syndrome Primary orbital tumor Medial rectus entrapment (blowout fracture) Entrapment of the inferior rectus (blowout fracture) Myasthenia gravis Third nerve palsy with or without aberrant innervation Nystagmus blockage syndrome (in congenital and latent nystagmus) Superior division third nerve palsy Ocular neuromyotonia Partial third nuclear lesion (very rare) Orbital disorders (orbital varix, infiltrative lesions) Brown syndrome (congenital, acquired) Posterior internuclear ophthalmoplegia of Lutz (pseudo-sixth) Congenital extraocular muscle fibrosis or muscle absence Pseudo–sixth cranial nerve palsy of Fisher Double elevator palsy (monocular elevator deficiency); controversial in origin Rippling muscle disease Sagging eye syndrome (see discussion in section on sixth nerve mimics) Sagging eye syndrome (see section in chapter) Spasm of the near reflex (near triad) (accompanied by miosis) Other Causes Stiff person syndrome (associated with abduction deficits, hypometric sac- Chronic progressive external ophthalmoplegia cades) Miller Fisher syndrome Thyroid eye disease (often involves medial rectus, leading to restrictive Botulism abduction defect) Monocular supranuclear gaze palsy Tonic convergence spasm (part of dorsal midbrain syndrome) Stiff person syndrome Wernicke encephalopathy (bilateral abducens palsies) Superior oblique myokymia Dissociated vertical deviation (divergence) Wernicke encephalopathy When a patient with incomitant strabismus fixates on an object with Vertical one-and-a-half syndrome the nonparetic eye, the angle of misalignment is referred to as the pri- mary deviation. When the patient fixates with the paretic eye, the angle of misalignment is referred to as the secondary deviation. Secondary diplopia. When one of the subjective methods for test performance is deviation is always greater than primary deviation in incomitant stra- used, it is important to remember that the hypertropic eye views the bismus because of the Hering law of dual innervation; it may mislead lower image. The examiner should also be aware of the pitfalls of the the examiner to believe that the eye with the greater deviation is the three-step test—namely, the conditions in which the rules break down. weak one (Fig. 18.20). These include restrictive ocular myopathies (Box 18.5), long-standing Often, comitant strabismus is ophthalmological in origin. In strabismus, skew deviation, and disorders involving more than one contrast, incomitant strabismus is neurological (though a common muscle. The test is most helpful for confirming the pattern of a fourth exception to this generalization is skew deviation [discussed later]). As nerve palsy. an example of incomitance, a right lateral rectus palsy will cause an Step 1 determines which eye is higher (hypertropic) in primary esotropia that increases upon looking to the right, the side of the weak position. The patient’s head may have to be repositioned (con- muscle, and decreases upon looking to the left, opposite side where the trolled primary position) to neutralize any compensatory tilt. If weak muscle is out of its plane of action (see Fig. 18.15, A). Similarly, the right eye is higher, the weak muscle is either one of the two with a right medial rectus weakness, an exotropia will be present that depressors of the right eye (inferior rectus or superior oblique) or increases on looking left and decreases in right gaze (see Fig. 18.15, B). one of the two elevators of the left eye (superior rectus or inferior Of importance to accurate neurological localization and diagnosis is oblique). the concept of spread of comitance with a chronic lesion, which means Step 2 determines whether the hypertropia increases on left or right that there is a tendency for a chronic ocular deviation to “spread” to gaze. If a right hypertropia increases on left gaze, the weak muscle all fields of gaze, thereby becoming comitant over time; thus, the usual is either the depressor in the right eye, which acts best in adduction localizing rules of comitance may not apply. (i.e., the superior oblique), or the elevator in the left eye, which acts The Parks-Bielschowsky three-step test enables the examiner to best in abduction (i.e., the superior rectus). assess the pattern of a vertical misalignment of the eyes to identify the Step 3 determines whether the hypertropia changes when the head paretic muscle. Eight muscles are involved in vertical eye movements: tilts to the left or the right. If a right hypertropia increases on head four elevators (two superior recti and two inferior obliques) and four tilt right, the weak muscle must be an intortor of the right eye depressors (two inferior recti and two superior obliques). The three- (superior oblique); if it increases on head tilt left, the weak muscle step test endeavors to determine whether a single paretic muscle is must be an intortor of the left eye (superior rectus). responsible for vertical diplopia (see Fig. 18.17). Using the cover-un- Three additional optional steps have been described: cover test, which is objective, or one of the subjective tests such as the Step 4 uses one of several techniques (e.g., double Maddox rod, visual red glass test, the physician can perform the three-step test for vertical field blind spots, indirect ophthalmoscopy, fundus photography) #*" #
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212 PART I Common Neurological Problems attempted right gaze, the patient turns the head farther to the right (see Fig. 18.21, A). With a right superior oblique palsy, the head tilts forward and to the left (see Fig. 18.21, B). The rule is as follows: The head turns or tilts in the direction of action of the weak muscle. Careful examination of the eyelids and external appearance of the eyes in the presence of diplopia can provide clues for accurate localiza- tion (Box 18.6). Visual acuity, stereopsis, color vision, and confron- tation visual fields should be checked carefully and separately in each eye, along with a complete neurological examination. Nonfatigable limitation of eye movements may suggest a restric- tive process such as a tethered extraocular muscle (entrapment) or an infiltrative process such as with thyroid eye disease (TED), idio- pathic orbital inflammatory syndrome (IOIS), lymphoma, and so on. Assessment for such restriction is performed with forced duction test- ing under topical anesthesia. The use of phenylephrine hydrochloride A eye drops beforehand reduces the risk of subconjunctival hemorrhage. Right eye Left eye Although this test is in the realm of the ophthalmologist, it may be performed in the office using topical anesthesia and a cotton-tipped SR (IO) SR (IO) applicator, but great care must be taken to avoid injuring the cornea. SR IO IO SR The causes of restrictive myopathy are listed in Box 18.5; however, any cause of prolonged extraocular muscle paresis can result in contracture of its antagonist muscle. LR MR MR LR Localization and Diagnosis IR SO SO IR Comitant Congenital Strabismus B IR (SO) IR (SO) Comitant strabismus occurs early in life; the magnitude of misalign- Fig. 18.14 A, The nine diagnostic positions of gaze used for testing ver- ment (deviation) is similar in all directions of gaze, and each eye has sions (saccades and pursuit). B, Ductions are used to test the isolated a full range of movement (i.e., full ductions). Some form of comitant action of each of the six muscles of each eye (the other five muscles ocular misalignment is present in 2% to 3% of preschool children are assumed to be functioning normally). Pure elevation (supraduction) and some form of amblyopia in 3% to 4% (Hunter, 2005). Likely and depression (infraduction) of the eyes are predominantly functions this occurs because of failure of central mechanisms in the brain that of the superior (SR) and inferior (IR) rectus muscles, respectively, with keep the eyes aligned. Infantile (congenital) esotropia may be associ- some help from the oblique muscles. That is, the eyes are rotated ated with maldevelopment of the afferent visual system, including the directly upward primarily by the SR with some help from the inferior visual cortex, and presents within the first 6 months of life; those with oblique (IO). The eyes are rotated directly downward primarily by the IR comitant esotropia of more than 40 prism diopters (20 degrees) do with some help from the superior oblique (SO). LR, Lateral rectus; MR, not “grow out of it” and require surgical correction (Donahue, 2007). medial rectus. Evidence using cortical motion visual evoked potentials indicates that early correction of strabismus (before 11 months of age) improves to determine whether ocular torsion is present. Establishing the visual cortical development (Gerth et al., 2008). Esotropia after the age degree and direction of ocular torsion, if any, can differentiate a of 3 months is abnormal and, if constant, usually associated with devel- skew deviation from a superior oblique palsy. Because the primary opment delay, cranial facial syndromes, or structural abnormalities of action of the superior oblique muscle is incyclotorsion (see Table the eye. It should be corrected early unless contraindicated by one of 18.1), typically an acute palsy results in approximately 5 degrees of the previously mentioned underlying conditions. Intermittent exotro- excyclotorsion of the affected eye due to unopposed action of the pia is common and can be treated with exercises, minus-lens spectacles ipsilateral inferior oblique muscle; greater than 10 degrees suggests to stimulate accommodation, or surgery. bilateral involvement. If either eye is intorted, a superior oblique Comitant esotropia that manifests between the ages of 6 months palsy is not responsible and the patient may have a skew deviation and 6 years (average 2½ years) is usually caused by hyperopia (far- (Donahue et al., 1999). sightedness), resulting in accommodative esotropia: such children with Step 5 is helpful in the acute phase. If the deviation is greater on excessive farsightedness must accommodate to have clear vision; the downgaze, the weak muscle is a depressor; if it is worse on upgaze, constant accommodation causes excessive convergence and leads to the weak muscle is likely to be an elevator. This fifth step is helpful persistent esotropia. Accommodative esotropia responds well to spec- only in the acute stage, because with time the deviation becomes tacle correction alone. Evidence indicates that high-level stereopsis more comitant. is restored in these children (unlike those with uncorrected infantile Step 6 involves assessing the size of the vertical deviation in a esotropia) if treatment is initiated within 3 months of the onset of con- supine position. If the deviation improves in a supine position, a stant esotropia (Fawcett et al., 2005). skew deviation is more likely than a superior oblique palsy (Wong, New-onset strabismus at school age (after age 6 years) is unusual 2015). and warrants evaluation for a neurological disorder. Occasionally chil- Head position, eyelids, and other exam techniques (Video 18.1). dren with Chiari malformations or posterior fossa tumors present with Patients with diplopia may compensate by tilting or turning the head in isolated esotropia before other symptoms or signs develop. Features the direction of action of the weak muscle to move the eyes into a posi- that suggest a structural cause for esotropia include presentation after tion where the weak muscle is not needed (Fig. 18.21). For example, with age 6, complaints such as diplopia or headache, incomitance in hori- right lateral rectus palsy, the head is turned slightly to the right; then, on zontal gaze, esotropia greater at distance than near, and neurological #*" #
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 CHAPTER 18 Neuro-Ophthalmology: Ocular Motor System 213 TABLE 18.3 Causes of Ophthalmoplegia and Gaze Palsies Site Disorder Muscle Ocular myopathies: Congenital myopathies: Central core Centronuclear (myotubular) Fiber-type disproportion Multicore (ptosis, spares EOM) Nemaline Neurocristopathy (EOM fibrosis) Oculopharyngodistal myopathy (Satoyoshi myopathy) Autosomal dominant Autosomal recessive Reducing body myopathy (ptosis, spares EOM) Dystrophies: Myotonic dystrophy (ptosis, usually spares EOM) Oculopharyngeal dystrophy Inflammatory myopathies: Dermatomyositis Giant cell arteritis (typically by muscle ischemia) Idiopathic orbital inflammatory syndrome (orbital pseudotumor) Metabolic and toxic myopathies (act at multiple sites, e.g., anticonvulsants) Mitochondrial cytopathy: Chronic progressive external ophthalmoplegia (CPEO) CPEO-like syndrome: mitochondrial toxicity in long-standing AIDS and long exposure to HAART Kearns-Sayre syndrome Pearson syndrome POLIP syndrome (polyneuropathy, ophthalmoplegia, leukoencephalopathy, intestinal pseudo-obstruction) Infiltrative disorders (thyroid, amyloid, metastases, congenital familial fibrosis, cystinosis) High myopia (large globes cause mechanical restriction) Trauma (orbital entrapment) Neuromuscular Myasthenia gravis junction Toxins (e.g., botulism, cosmetic botulinum toxin, organophosphates) Lambert-Eaton syndrome (rarely affects EOM, mainly causes ptosis) Ocular motor nerves See Chapter 103 Gaze palsies Nuclear and paranuclear: Brainstem injury (vascular, multiple sclerosis, neuromyelitis optica, encephalitis, paraneoplastic, toxins, tumor) Familial congenital gaze palsy Glycine encephalopathy (nonketotic hyperglycinemia: hiccups, seizures, apneic spells) Internuclear ophthalmoplegia Leigh disease Machado-Joseph disease (SCA3) Maple syrup urine disease Möbius and Duane syndromes (agenesis of cranial nerve nuclei) One-and-a-half syndrome Progressive encephalitis with rigidity and myoclonus (PERM), a variant of the stiff person syndrome Spinocerebellar degeneration Tangier disease Vitamin E deficiency Prenuclear: Monocular “supranuclear” elevator palsy Ocular tilt reaction Skew deviation Vertical one-and-a-half syndrome Supranuclear (predominantly horizontal): Acutely, after hemispheric stroke: Congenital ocular motor apraxia or congenital saccadic palsy Ipsiversive or contraversive (wrong-way eyes) Gaucher disease (types 2 and 3) Ictal (transient, adversive) Juvenile-onset GM2 gangliosidosis (mimics juvenile SMA) Postictal (transient, ipsiversive) Paraneoplastic disorders Continued #*" #
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214 PART I Common Neurological Problems TABLE 18.3 Causes of Ophthalmoplegia and Gaze Palsies—cont’d Site Disorder Supranuclear (predominantly vertical): Adult-onset GM2 gangliosidosis (mimics multisystem atrophy or spinocerebellar degeneration) (V > H) Amyotrophic lateral sclerosis (rare, V > H) Autosomal dominant parkinsonian-dementia complex with pallidopontonigral degeneration (dementia, dystonia, frontal and pyramidal signs, urinary incontinence) Cerebral amyloid angiopathy with leukoencephalopathy Congenital vertical ocular motor apraxia (rare) Dentatorubral-pallidoluysian atrophy (autosomal dominant, dementia, ataxia, myoclonus, choreoathetosis) Diffuse Lewy body disease (ophthalmoplegia may be global) Dorsal midbrain syndrome Familial Creutzfeldt-Jakob disease (U > D) Familial paralysis of vertical gaze Gerstmann-Sträussler-Scheinker disease (U > D, dysmetria, nystagmus) Guamanian Parkinson disease-dementia complex (Lytico-Bodig disease) HARP syndrome (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, pallidal degeneration) Hydrocephalus (untreated, decompensated shunt) Joseph disease Kernicterus (U > D) Late-onset cerebellopontomesencephalic degeneration (D > U) Neurovisceral lipidosis; synonyms: DAF syndrome (downgaze palsy-ataxia-foamy macrophages); dystonic lipidosis; Niemann-Pick disease type C (initially loss of downgaze, which ma