This chapter covers eye movement disorders that are characterized by intact alignment, but in which the eyes either have restricted motility, move too slowly, or are misdirected. In neuro-ophthalmic terminology, these include horizontal and vertical conjugate gaze limitations, voluntary smooth pursuit and saccadic deficits, and involuntary conjugate gaze deviations.
These conditions tend to result from impaired supranuclear input upon the ocular motor nuclei. Thus, for the most part, third, fourth, and sixth nerve function, as well the vestibulo-ocular reflex (VOR), are intact, except in the situations noted. In contrast, disorders in which the eyes tend to be misaligned are covered in Chapters 15 and 18 . In Chapter 17 , conditions characterized by excessive or inaccurate saccades are reviewed.
Types of Conjugate Eye Movements
Humans have a large field of vision but a very small area of high spatial resolution acuity, subserved by the fovea. The purposes of having eye movements are to maintain constant foveation of an object of interest or to foveate a target quickly. Therefore, different classes of eye movements are necessary to achieve this goal during self- or environmental motion. The four major types of conjugate eye movements include saccades, pursuit, the VOR, and optokinetic nystagmus (OKN). Vergence movements are dysconjugate and allow for foveation of near targets by converging or distance ones by diverging ( Table 16.1 ). Because saccadic and pursuit abnormalities constitute the majority of the voluntary conjugate gaze abnormalities, they are emphasized in this chapter, and their anatomy and physiology is discussed in great detail. The VOR and OKN deficits are typically not considered conjugate gaze abnormalities, so they are discussed in more detail in Chapter 17 .
|Eye Movement Type||Purpose||Important Supranuclear Structure(s)||Important Supranuclear Structure Receives Major Input From|
|Saccades||Rapid gaze shift||Omnipause neurons |
parapontine reticular formation (PPRF)
rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)
|Cortical eye fields |
|Pursuit||Follow a slowly moving object||Vestibular nuclei||Frontal and supplementary eye fields |
Occipito-temporal-parietal area (V5)
|Vestibuloocular reflex||Coordinate eye position during head movements||Vestibular nuclei||Semicircular canals|
|Optokinetic nystagmus||Coordinate eye movements when environment moves||Vestibular nuclei||Occipito-parietal pursuit area and accessory optic nuclei|
Supranuclear eye movement disorders result from damage to the structures responsible for initiating, tuning, or calibrating ocular motor control, while the ocular motor nuclei (nuclear structures) and exiting fascicles and nerves (infranuclear structures) are spared.
Saccades . Saccades are fast conjugate eye movements designed to refixate both foveas on a novel target (see Fig. 2.27 and ). They have a peak velocity of up to 700 degrees per second, and they must be fast to minimize the time during the saccade in which foveation is not possible. There are several subtypes of saccades. Voluntary saccades are intentional eye movements toward a remembered target or during a search. Reflexive saccades occur in response to the sudden appearance of a new target in the retinal periphery or to a sudden noise. Spontaneous saccades, which may occur during speech or at rest during the darkness, have no particular goal.
Pursuit . On the other hand, smooth pursuit eye movements maintain both foveas conjugately on a slowly moving visual target (see Fig. 2.26 and ). The goal of the pursuit system is to generate eye velocities that are similar to the target speed. Accurate pursuit can be achieved if the target is moving at less than 50 degrees per second.
Vestibulo-ocular reflex (VOR) . These eye movements stabilize a retinal image during head movement. The VOR (see Fig. 2.28 and ) is elicited by moving the patient’s head while asking him or her to maintain fixation on the examiner’s nose. Ice water irrigation of the ears (cold caloric testing) directly tests the horizontal VOR (see Fig. 2.41 ).
Optokinetic nystagmus (OKN) . A slow pursuit eye movement followed by a fast corrective saccade occurs when the surrounding visual field moves over the retina. OKN is readily seen at the bedside when the patient views repetitive targets (e.g., stripes) that are moved in front of the patient’s eyes (see Fig. 2.30 and ).
Most patients with conjugate gaze abnormalities offer only vague visual complaints such as blurriness or dizziness when looking up or down. Those with downgaze palsies may complain that they are unable to read, go down steps, or eat, but such patients are usually unaware that the problem stems from an inability to look down. Similarly, those with conjugate upgaze pareses might say they have trouble seeing bookshelves or other objects above eye level. Few actually complain that they are unable to look sideways or vertically, although exceptions occur. Some are visually asymptomatic, and the ocular motility deficit is detected on examination.
Smooth pursuit can be tested at the bedside by having the patient follow a slowly moving target with both eyes. The slow phase of OKN and suppression of the VOR by visual fixation are two other ocular motor functions related to smooth pursuit eye movements. The relative speed, latency, and accuracy of saccades can be evaluated during refixation from eccentric gaze to a central target. Spontaneous saccades during the history-taking should also be observed. Chapter 2 also reviews these examination techniques, with figures, for testing conjugate gaze.
Gain is the ratio of eye to target position, and, when pursuit is defective, the saccadic system helps keeps the foveae on target with “saccadic pursuit.” When gain is decreased, the eyes fall behind the target, and the saccadic system makes corrective catch-up movements. Gain may also be increased with a cerebellar lesion. Abnormal pursuit or marked asymmetries may be better appreciated by observing the slow (pursuit) phase of OKN with an optokinetic stimulus. Failure to suppress the VOR (VORS) may be evident when slippage of the eyes with corrective saccades occurs (see Fig. 2.29 ). A deficit in VORS is almost never seen without an ipsilateral deficit in pursuit.
Defective saccades are often characterized by slow velocities that cannot be feigned by individuals with normal ocular motor systems. Some patients with defective saccades will use a compensatory head thrust in an attempt to shift gaze (see Acquired Ocular Motor Apraxia ). When saccades are completely absent, a conjugate gaze palsy results. Sometimes the fast phase of OKN is noted to be defective. The supranuclear nature of some pursuit and saccadic deficits can be proven by enhancing the ocular excursions with the VOR, because direct connections exist between the semicircular canals and ocular motor nuclei.
The remainder of the neuro-ophthalmic and neurologic examinations should be used to screen for cortical deficits such as aphasia or hemianopia and brainstem and cerebellar abnormalities such as facial palsies or incoordination. Finally, evidence of a degenerative process such as bradykinesia, tremor, or chorea should be sought.
One method for distinguishing supranuclear conjugate gaze disorders is to divide them into those that cause primarily horizontal vs vertical defects, although there is considerable overlap ( Boxes 16.1–16.4 ). Those in the horizontal plane tend to localize to cerebral cortex or pontine lesions, while those in the vertical plane usually localize to midbrain disturbances. Then the type of disorder, such as a conjugate gaze limitation, smooth pursuit and saccadic deficit, or conjugate gaze deviation, should be determined. Since conjugate gaze limitations and smooth pursuit and saccadic abnormalities are related, they are discussed within the Horizontal Conjugate Gaze Deficits and Vertical Gaze Limitations sections. When supranuclear gaze defects in all directions are present, the cause is often a degenerative neurologic disorder.
Frontal eye fields: saccades
Occipito-parietal junction: pursuit
Acquired ocular motor apraxia
Paramedian pontine reticular formation
Sixth nerve nucleus
Midbrain and medullary lesions
Congenital ocular motor apraxia
Other neurologic diseases
Gaucher disease *
* Disorders whose ocular motility abnormality may mimic congenital ocular motor apraxia.
Progressive supranuclear palsy (late)
Wernicke’s encephalopathy and Leigh disease
Drugs (see Table 16.3 )
Frontal eye field
Periodic alternating gaze deviation (“ping-pong” gaze)
Paramedian midbrain–thalamic stroke
Pineal region and thalamic masses
Midbrain downgaze paresis
Limitation of upgaze in elderly
Other neurologic disorders
Progressive supranuclear palsy
Niemann–Pick type C disease *
* Disorders whose ocular motility abnormality may mimic congenital ocular motor apraxia.
Amyotrophic lateral sclerosis
Benign, tonic form in infancy
Horizontal Conjugate Gaze: Neuroanatomy
The major cortical control of horizontal saccadic eye movements, especially intentional ones, lies in the frontal eye fields (Brodmann area 8). Each hemisphere has a frontal eye field located in the posterior portion of the second frontal gyrus and the adjacent part of the precentral gyrus and sulcus ( Fig. 16.1 ). In one study of awake patients evaluated with subdural electrodes for epilepsy surgery, electrical stimulation of the frontal eye fields caused contralateral horizontal conjugate eye movements in all patients. The ocular deviation was usually saccadic and accompanied by head versions. Two other cortical areas (see Fig. 16.1 ) are capable of triggering other types of saccades: (1) the supplementary eye field in the supplementary motor area of the frontal lobe is important for generating saccades coordinated with head or body movements or motor programs involving several successive saccades and (2) the parietal eye field, located in the posterior parietal cortex, is instrumental in producing reflexive saccades to visual targets. Saccades are likely controlled by a neural network connecting these areas.
These cortical areas mediating saccades send supranuclear fibers that decussate at the level of the oculomotor and trochlear nuclei before reaching the contralateral omnipause neurons (OPN) in the nucleus raphe interpositus of the pons. Between saccades, OPN tonically inhibit the burst neurons in the paramedian pontine reticular formation (PPRF) to facilitate fixation and reduce unwanted saccades. In one model, saccades are generated when signals from the supranuclear cortical and brainstem neurons inhibit the OPN, allowing the burst neurons in the PPRF to fire ( Fig. 16.2 ). Each PPRF also receives connections from the deep layer of the contralateral superior colliculus, which may be involved in the selection of targets for foveation in retinotopic coordinates. Located near the midline just ventral and rostral to each sixth nerve nucleus (see Chapter 15 ), each PPRF is the premotor center for generating horizontal saccadic eye movements. It is unlikely that omnipause cells are directly responsible for termination of saccades, which may instead be related to fastigial nucleus influence over the inhibitory burst neurons.
Each PPRF innervates the ipsilateral sixth nerve nucleus, which in turn innervates the ipsilateral lateral rectus muscle. The sixth nerve nucleus also supplies the interneurons, which immediately cross the midline and then climb within the medial longitudinal fasciculus (MLF) to reach the contralateral medial rectus subnucleus within the oculomotor complex in the midbrain (see Fig. 16.2 ). The PPRF also sends fibers to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the midbrain (see Vertical Conjugate Gaze: Neuroanatomy ). Thus, the PPRF primarily coordinates horizontal but also has an influence upon vertical eye movements.
Information regarding eye position and maintenance of eccentric gaze is mediated by a neural integrator, consisting of neurons subserving horizontal (nucleus prepositus hypoglossi (NPH) and medial vestibular nuclei (MVN)) and vertical (interstitial nucleus of Cajal (inC)) eye movements (see also Chapter 17 ). After an eccentric saccade, viscoelastic forces in the orbit tend to drag the eye back into primary position. To counter this, neural integrator neurons modulate burst neuron activity in the PPRF and riMLF to maintain eccentric gaze. The dorsal vermis and the fastigial nuclei of the cerebellum are involved in the calibration of saccadic amplitude and fine tuning.
Popular in detailed eye movement evaluations and as nonspecific biomarkers (see later discussion) in schizophrenia, for example, antisaccades are conjugate eye movements directed away from a visual stimulus. Individuals are shown a target in the periphery and instructed to look in the opposite direction. Antisaccades require the suppression of reflexive saccades toward the target, and this inhibition is believed to be mediated by the dorsolateral prefrontal cortex. Evaluation of the saccadic system has become an effective means of diagnosing concussion and mild traumatic brain injury. A tool called the King–Devick test is used, in which the subject is asked to rapidly read a series of unevenly spaced numbers while being timed. Poor individual performance versus baseline prehead injury scores have been associated with concussion and postconcussive memory impairment, because areas such as the dorsolateral prefrontal cortex are important for both saccades and immediate memory. Prolongation of the intersaccadic interval (ISI) and an increase in the number of saccades are the most common reasons for longer times to complete the King-Devick test following a concussion.
Two descending parallel pathways mediate smooth pursuit ( Fig. 16.3 ). In one, cortical signals arise from the occipito-temporal-parietal junction in Brodmann areas 19, 37, and 39 (area V5, see Fig. 9.7B ), which are homologous to monkey areas MT (middle temporal) and MST (medial superior temporal). Although areas 19, 37, and 39 are part of the dorsal stream, or magnocellular pathway, responsible for motion and spatial analysis of visual information (see Chapter 9 ), smooth pursuit is independent of motion detection and spatial attention. The other pursuit pathway originates in the frontal lobes in the caudal frontal eye field (FEF) and supplementary eye field (SEF) (see Fig. 16.1 ).
These descending pathways for smooth pursuit then connect ipsilaterally with regions in the pons, the dorsolateral pontine nucleus (DLPN), and the nucleus reticularis tegmenti pontis (NRTP). From these areas, a double decussation occurs, as these regions innervate contralateral cerebellar structures such as the flocculus, paraflocculus, vermis, and fastigial nucleus, which in turn send inhibitory fibers via the inferior cerebellar peduncle to the medial vestibular nucleus, which then excites the contralateral sixth nerve nucleus. The stimulated sixth nerve nucleus is ipsilateral to the MST/FEF/SEF that generated the initial pursuit command (see Fig. 16.3 ). From the vestibular nuclei, efferents travel directly to the ocular motor nuclei, and indirectly via the NPH and inC, so that the new eye position can be maintained. Note the smooth pursuit system is independent of the PPRF, so if pursuit is affected, saccades may be spared, or vice versa. The pursuit pathways are extensive; therefore abnormalities which may be influenced by age, medications, and alertness are generally nonlocalizing. However, saccadic pursuit vertically and horizontally should raise suspicion for flocculus or paraflocculus dysfunction, and notable horizontal asymmetry indicates ipsilesional pathology.
Vestibuloocular Reflex and Optokinetic Nystagmus
Fibers mediating the VOR arise from the posterior, anterior, and horizontal semicircular canals, synapse in the vestibular nuclei, travel rostrally via the MLF (with two additional upward or “antigravity” pathways for the anterior canals), and pass through but do not synapse in the caudal portion of the PPRF; then finally horizontal canal afferents arrive and synapse at the sixth nerve nucleus, and anterior and posterior canal afferents proceed to the third and fourth nuclei. The cerebellum is involved in the suppression of the VOR. The generation of OKN relies first upon cortical and subcortical areas which mediate smooth pursuit, then upon structures responsible for the generation of saccades, as described previously.
The pathways for the VOR and OKN are discussed in more detail in Chapter 17 .
Horizontal Conjugate Gaze Deficits
Deficits Caused by Cortical Lesions
Saccades . Unilateral frontal eye field lesions tend to cause contralateral saccadic eye movement impairment ( Fig. 16.4 ), oftentimes with hemiparesis on the same side as the direction of the gaze paresis. Acutely, the eyes may be deviated ipsilaterally toward the lesion (see Abnormal Horizontal Conjugate Gaze Deviations ).
Pursuit . Unilateral lesions within the occipito-temporal-parietal junction or the frontal and supplementary eye fields can cause a directional pursuit deficit, in which smooth pursuit of targets moving ipsilaterally toward the lesion is affected. Less commonly, unilateral lesions in the occipito-temporal-parietal junction and in striate cortex may also cause retinotopic pursuit abnormalities of targets in the contralateral hemifield. Retinotopic defects are location-dependent and uninfluenced by the direction of the target motion. Thus, in this situation, pursuit is abnormal in both directions in the contralateral hemifield. In a third type of pursuit defect, craniotopic, the patient cannot generate contralaterally directed pursuit eye movements past the midline of the head. For instance, a patient with such a defect due to a left parietal lesion can pursue a rightward moving target only until the eyes reach midline.
In practice, cortical ipsilesional pursuit defects are most commonly associated with lesions at the occipito-parietal-temporal junction. Reflecting this, optokinetic responses can be defective in patients with parietal lobe lesions with contralateral hemianopia ( ). When the optokinetic targets are moved toward the side of the lesion, either the pursuit component is impaired, the amplitudes of the pursuit and saccades are smaller, or there is no corrective saccade.
Acquired ocular motor apraxia . Bilateral parieto-occipital lesions may lead to an acquired ocular motor apraxia, characterized by an absence or severe impairment of smooth pursuit, optokinetic responses, and visually guided saccades. Because the eyes appear not to move, the term “spasm of fixation” has also been used. However, reflexive saccades may be preserved, justifying the use of the term apraxia. When ocular motor apraxia is combined with optic ataxia and simultanagnosia, the symptom complex is known as Balint syndrome, which is discussed in detail in Chapter 9 (see Figs. 9.9 and 9.10 and ).
The combination of bilateral parietooccipital injury combined with bilateral lesions affecting both frontal eye fields, as in watershed ischemia, for instance, can cause a more severe form of acquired ocular motor apraxia. Voluntary saccades and pursuit in all directions may be completely paralyzed. The ocular motility deficit mimics the congenital type (see later discussion), as patients may use a head thrust to aid refixation. In some cases reflexive saccades are also affected, and in such instances the term ocular motor paresis may be preferred over apraxia.
Acquired ocular motor apraxia may also be seen in a number of progressive and inherited neurologic diseases (see Box 16.1 and later discussion).
Deficits Caused by Pontine Lesions
A lesion in the pons is the most common location for a brainstem disturbance that causes a horizontal gaze deficit, and there are frequently other accompanying signs. Pontine lesions are suggested when a conjugate gaze paresis is bilateral or accompanied by an internuclear ophthalmoplegia (INO), ipsilateral facial paresis, contralateral hemiparesis, or skew deviation and when vertical and convergence movements (i.e., midbrain mediated processes) are preserved.
Conjugate gaze paresis . Two types of pontine lesions may result in a conjugate gaze paresis ( ):
PPRF. Lesions restricted to the PPRF cause loss of all ipsilateral horizontal rapid eye movements such as voluntary and involuntary saccades and quick phases of nystagmus. Smooth pursuit and the VOR may be spared in selective lesions of the rostral portion of the PPRF.
Sixth nerve nucleus. A lesion of the sixth nerve nucleus, by damaging neurons innervating the ipsilateral lateral rectus muscle and the interneurons for the contralateral medial rectus, will cause an ipsilateral conjugate gaze palsy. Because of the anatomical proximity of the genu of the facial nerve to the sixth nerve nucleus (see Chapters 14 and 15 ), a nuclear sixth nerve palsy is often accompanied by ipsilateral facial weakness in the facial colliculus syndrome ( Fig. 16.5 ). All voluntary and reflexive ipsilateral conjugate eye movements are eliminated.
Any combination of bilateral lesions affecting either the PPRF or sixth nerve nuclei will cause a bilateral conjugate gaze palsy ( Fig. 16.6 , ).
In patients with pontine horizontal gaze palsies who attempt to look in the direction of the palsy, upward vertical or oblique movements of both eyes are often seen (see Fig. 16.5B ). The misdirection or substitution movement may be explained by compensatory contraction or overaction of the obliquely acting extraocular muscles. In addition, some observers have documented abnormal oblique misdirection and slowing of vertical saccades in patients with lesions of the PPRF. This finding, which is an inconsistent one, has been attributed to disruption of the caudal PPRF’s influence on the riMLF.
One-and-a-half syndrome . This highly localizing ocular motility disorder is characterized by a conjugate gaze palsy to one side accompanied by an ipsilateral internuclear ophthalmoplegia when the patient looks to the other side ( Fig. 16.7 , ). The name of the syndrome derives from the absence of conjugate eye movements in one direction and only preservation of abduction in the other direction. In primary gaze the eyes may be exotropic, with lateral deviation of the eye with intact abduction. The association of one-and-a-half syndrome or bilateral INOs and exotropia has been termed paralytic pontine exotropia . Convergence is often preserved. Because of the proximity of the descending central tegmental tract (part of Mollaret’s triangle) to the PPRF and sixth nucleus, oculopalatal tremor (see Chapter 17 ) may be seen months after the injury.
The one-and-a-half syndrome is caused by involvement of the PPRF or sixth nerve nucleus, causing the conjugate gaze paresis, combined with a lesion affecting the just-crossed MLF ( Fig. 16.8 ), which causes the INO (see Chapter 15 ). A lesion of the PPRF can generally be distinguished from one affecting the sixth nerve nucleus by the preservation of the VOR when the PPRF is involved. However, occasionally the VOR pathways are also damaged with PPRF lesions, given the proximity of these fibers. A one-and-a-half syndrome combined with a facial palsy due to involvement of the seventh nerve fascicle has been termed the eight-and-a-half syndrome.
Foville syndrome . A lesion in the caudal tegmental pons may cause a facial paralysis, conjugate gaze paresis, and contralateral hemiparesis by disrupting the fascicle of the seventh nerve, the PPRF or sixth nerve nucleus, and the corticospinal tract, respectively. This localizing combination of findings, described by Foville, is one of the crossed brainstem syndromes.
Locked-in syndrome . Large bilateral lesions almost transecting the pons may cause a neurologic state characterized by quadriplegia, absence of horizontal eye movements, and mutism but preservation of vertical eye movements, blinking, and consciousness. Patients in this “locked-in” state use these preserved functions to communicate, but they are often mistakenly diagnosed with coma. The basis pontis, at the level of the sixth nerve nuclei, is the area most commonly affected.
Defective smooth pursuit . Unilateral lesions of the dorsolateral pons have been associated with ipsilateral smooth pursuit deficits, without considerable abnormalities in saccades or the VOR. These findings confirm the importance of pontine structures in the pathways for smooth pursuit described previously (see Fig. 16.3 ).
Etiology . In older adults the most frequent cause of a pontine horizontal gaze palsy is ischemia in the distribution of one of the pontine paramedian penetrating arteries arising from the basilar artery. Atherosclerosis is by far the most common cause, but vasculitis due to giant cell arteritis, for example, may be responsible. In younger adults, demyelinating processes such as multiple sclerosis are the most common etiology (see Fig. 16.6 ). Other considerations in adults include hemorrhages due to hypertension or cavernous angiomas ( Fig. 16.9 ). Alcoholism, malnutrition, and overly rapid correction of hyponatremia may result in central pontine myelinolysis.
In contrast, mid- and lower brainstem neoplasms such as pontine gliomas or medulloblastomas are the most common cause in children. Möbius syndrome (see Chapter 14 ), when it affects the sixth nerve nucleus, may cause horizontal conjugate gaze palsies.
Caution should be applied when diagnosing pontine lesions in this setting, because pontine horizontal gaze palsies can be mimicked by the Fisher variant of Guillain–Barré syndrome, myasthenia gravis, and thyroid eye disease. Thus, if neuroimaging is normal, these peripheral nerve, neuromuscular junction, and myopathic disorders should be considered (see Chapters 14 and 18 ).
Horizontal Gaze Deficits Caused by Other Posterior Fossa Lesions
Midbrain . Rarely conjugate horizontal saccades and pursuit may be abnormal following damage to the midbrain tegmentum. Presumably the lesions affect descending horizontal gaze fibers destined for the PPRF. Zackon and Sharpe reported two such patients, each with adduction paresis of the eye ipsilateral to the lesion accompanied by paresis of contralateral saccades in the fellow eye. These patients also exhibited conjugate paresis of ipsilateral smooth pursuit. Isolated lesions of the superior colliculi, which are also rare, may cause defective reflexive saccades.
Medullary . Lateropulsion of saccades, characterized by overshoot of ipsilaterally directed saccades, undershoot of contralaterally directed saccades, and ipsilesional deviation during vertical saccades, is often a prominent ocular finding in lateral medullary lesions (see the discussion of other neuro-ophthalmic complications of Wallenberg syndrome in Chapter 13 ). Such patients also complain of body ipsipulsion, a sensation of the entire body being pulled toward the side of the lesion. Ipsilateral horizontal conjugate eye deviation (ocular lateropulsion) may also occur and is usually most obvious upon removal of visual fixation ( ). In other words, if the patient is asked to fixate straight ahead and close the eyes momentarily, the eyes drift ipsilaterally. As a result of this, upon eyelid opening a contralaterally directed refixation movement back to midline will be seen ( Fig. 16.10 ). Less commonly, an ipsilateral conjugate eye deviation is seen with the eyelids open.
Separate mechanisms may account for ipsipulsion of saccades and the conjugate eye deviation. However, each could result from damage to the inferior cerebellar peduncle and interruption of climbing fibers, which results in increased Purkinje (inhibitory) cell firing: (1) ipsipulsion of saccades from increased inhibition of the ipsilateral fastigial nucleus in the cerebellum and ultimately the relative hypoactivity of the contralateral PPRF and (2) conjugate gaze deviation either from increased inhibition of the ipsilateral vestibular nucleus or possibly from decreased tonic excitation of the contralateral PPRF with relative hyperactivity of the ipsilateral PPRF.
Lateral medullary lesions often also cause impaired smooth pursuit for targets moving contralaterally. This deficit likely reflects damage to the vestibular nucleus. Ocular contrapulsion has been described in association with medial medullary lesions because climbing fibers are disrupted caudally prior to their decussation.
Cerebellar . Lesions in the cerebellum can cause saccadic overshoot and undershoot (dysmetria) as well as an inability to sustain eccentric gaze with gaze-evoked nystagmus ( ). This results from damage to structures in the cerebellum responsible for the calibration of saccadic amplitude and gaze-holding, respectively (discussed previously). Cerebellar hemispheric lesions affecting the fastigial nucleus tend to cause ipsilateral saccadic hypermetria (overshoot) and contralateral saccadic hypometria (undershoot). Lesions involving the deep cerebellar white matter, especially those running through the uncinate fasciculus next to the superior cerebellar peduncle, may cause a contralaterally directed drift (contrapulsion). Cerebellopontine angle tumors may cause an ipsilateral smooth pursuit defect if the vestibular nucleus, flocculus, or inferior cerebellar peduncle is involved.
Familial horizontal gaze palsy and scoliosis . A rare autosomal recessive syndrome of horizontal gaze palsy and progressive scoliosis has also been described, and in most cases there is hypoplasia of the pons and cerebellar peduncles with anterior and posterior midline clefts of the pons and medulla. Patients have normal vertical movements with preservation of convergence, and congenital nystagmus is sometimes seen. Several responsible mutations of the ROBO3 gene on chromosome 11 have been identified, and congenital miswiring of the brainstem and spinal cord are suspected.
Other Horizontal Gaze Deficits
Saccadic palsy after cardiac surgery . Horizontal and vertical saccadic palsies have been reported as a complication of cardiac surgery, especially aortic valve replacement or aortic aneurysm repair ( and ). Neuroimaging often fails to disclose a responsible lesion in the cortex, brainstem, or cerebellum. Some authors have likened the ocular findings to those of progressive supranuclear palsy (see later discussion). Selective damage to the omnipause or excitatory burst neurons, superior colliculus, or cerebellum have been implicated, but the exact cause is unknown.
Congenital ocular motor apraxia . In this ocular motility disorder of young children, infants may first appear to be blind or have decreased peripheral vision because they have defective or absent horizontal saccades to novel visual stimuli ( ). Quick phases of OKN and the VOR are also diminished, but smooth pursuit and vertical eye movements are usually preserved. At 5 or 6 months of age, when they achieve better head and neck control and can sit unassisted, they begin to use horizontal head thrusts to shift fixation ( Fig. 16.11 ). Often initiating the sequence with an eyelid blink, patients move their heads rapidly toward a new visual target. Then the eyes slowly refixate. A final correction in head position sometimes then occurs, as the eyes are maintained on the target using the VOR. Congenital ocular motor apraxia is almost always symmetric and bidirectional in the horizontal plane, but there have been exceptional asymmetric and vertical cases. Generally, patients who display horizontal head thrusts have normal imaging or infratentorial imaging abnormalities, while patients with vertical head thrusts have supratentorial imaging abnormalities. Patients with impaired smooth pursuit and OKN slow phases are more likely to have abnormal magnetic resonance imaging (MRI) in either infratentorial or supratentorial areas. In many instances the head thrusting and defective saccades spontaneously improve as the child gets older, but in some cases the ocular motility disturbance may persist. Because there are many causes and a great deal of clinical heterogeneity (see later discussion), the exact pathologic substrate is unclear, although usually a defect in the saccadic system is implicated.
Two caveats regarding the use of the term congenital ocular motor apraxia should be mentioned:
Because in some instances both voluntary and some reflexive saccades are defective, the term apraxia, implying only voluntary saccades are affected, has been criticized. Other terms such as congenital saccadic palsy, intermittent horizontal saccade failure, and infantile-onset saccade initiation delay have been proposed. However, the term that Cogan originally coined is unlikely to be supplanted, having already been heavily imbedded in the neuro-ophthalmic vernacular.
Although some authors have applied the term congenital ocular motor apraxia to children of any age, we feel the term should be reserved for only those instances in which the motility disorder is present in infancy.
Congenital ocular motor apraxia is observed in three main clinical situations:
In the “benign” or “idiopathic” variety of congenital ocular motor apraxia, neuroimaging is normal and there is no readily identifiable explanation for the disorder. Although the neurologic examination and intellect are usually normal, occasionally associated neurologic defects include hypotonia, motor and speech delay, and ataxia. Many have infantile esotropia. Familial cases have also been reported. Parents should be informed that the afferent visual function of these children is normal.
Some patients with congenital ocular motor apraxia have a nonprogressive, noninherited structural abnormality of the brain, caused either by a developmental anomaly or prenatal or perinatal insult. These include dysgenesis of the cerebellar vermis or corpus callosum, inferior vermian hypoplasia, Dandy–Walker malformation ( Fig. 16.12 ), gray matter heterotopias, and perinatal ischemia.
A variety of genetic disorders with multisystem involvement may present in infancy with congenital ocular motor apraxia. These include Joubert syndrome (see Chapter 17 and Fig. 17.12 ), Jeune syndrome (nephronophthisis, asphyxiating thoracic dystrophy, retinal degeneration, and ataxia), and a subset of patients with Leber’s congenital amaurosis, a retinal dystrophy.
In contrast, we believe the term acquired ocular motor apraxia is more appropriate when a similar disorder of head and eye coordination is seen in older children presenting with progressive, degenerative, or inherited metabolic neurologic diseases (see the next section), for instance. The distinction may be difficult when children present with ocular motor apraxia at 6–12 months of age, at which time mild “congenital” and early “acquired” neurologic diseases may be confused. However, some diagnostic guidelines include (1) the voluntary ophthalmoparesis and head thrusts are almost always limited to the horizontal plane in congenital ocular motor apraxia and the acquired form due to Gaucher disease; (2) in contrast, the eye movement abnormalities and compensatory head movements are often in both the horizontal and vertical planes in ataxia-telangiectasia and spinocerebellar ataxias; and (3) they are primarily in the vertical plane in Niemann–Pick type C.
Other Neurologic Disorders Associated With Horizontal Gaze Deficits
Inherited cerebellar ataxias . These inherited diseases are divided into those which are autosomal dominant and those that are recessive. Diseases with slow saccades or ophthalmoparesis in the dominantly inherited category include the spinocerebellar ataxias (SCA) types 1 (inherited olivopontocerebellar atrophy), 2, 3 (Machado–Joseph disease) ( ), and 7. SCA 1, 2, 3, 6, and 7 make up about 80% of the SCAs, and each tends to have prominent neuro-ophthalmic features. A CAG trinucleotide repeat is responsible for each. Recessively inherited diseases with mild slowing of saccades include Friedreich ataxia, ataxia telangiectasia, and oculomotor apraxia types 1 and 2. The identification of the molecular basis of many of these disorders has allowed a genetic rather than a phenomenologic or pathologic classification. Disease severity, including degree of saccadic abnormality, in many cases is related to the number of trinucleotide repeats. Table 16.2 highlights the inherited cerebellar ataxias with defective saccades, including the localization of their genetic defects.
|Name||Genetic Locus||Slow Saccades/Ophthalmoparesis||Other Ocular Motor Features||Optic Atrophy||Retinal/Macular Degeneration||Other Neurologic and Systemic Features||References|
|SCA 1 (inherited OPCA, (formerly ADCA type I))||6p22–p23 with CAG repeats (ataxin 1 gene)||++||GEN with RN, saccadic pursuit, saccadic dysmetria||+/−||+/−||Pyramidal signs|
|SCA 2 (formerly ADCA type I)||12q23–24 with CAG repeats (ataxin 2 gene)||+++||No GEN, no saccadic dysmetria||+/−||−||Myoclonus, muscle fasciculations|
|SCA 3 (Machado–Joseph disease)||14q24.3–q32 with CAG repeats (ataxin 3 gene)||+/− |
Vertical more than horizontal
|SWJ, oscillations (flutter), impaired VOR gain, internuclear/nuclear ophthalmoplegia, saccadic pursuit, GEN with RN||+/−||Rare||Dystonia, rigidity, neuropathy, facial fasciculations, eyelid retraction|
|SCA 6||Translated CAG repeat expansion, calcium channel subunit (CACNA1A)||Spontaneous DBN, positional downbeat nystagmus, perverted head shaking nystagmus (i.e., DBN with horizontal head-shaking), saccadic pursuit, SWJ, GEN with RN||−||−||Pure cerebellar ataxia|
|SCA 7 (formerly ADCA type II)||3p14–21.1 with CAG repeats (ataxin 7 gene)||+++||saccadic dysmetria and pursuit, GEN with RN||−||++ |
(Defining feature; see Chapter 4 and Fig. 4.24 )
|Truncal, gait, and limb ataxia, dysarthria|
|Episodic ataxia 2||Loss of function mutation of calcium channel CACNA1A; CACNB4||−||Initially vertigo attacks with nystagmus; later, interictal ocular motor signs develop (e.g., GEN with RN, saccadic dysmetria, saccadic pursuit)||−||−||During initial attacks, patients are ataxic and ataxia becomes permanent later in the disease|
|Ataxia telangiectasia||Chromosome 11, ATM gene, normally screens for DNA damage and activates DNA repair mechanisms||++||SWJ, ocular flutter, intact VOR, head thrusts as in ocular motor apraxia||−||−||Conjunctival telangiectasias, sinopulmonary infections, neuropathy, high rates of malignancy (lymphomas leukemias, and breast cancer), elevated alpha-fetoprotein levels, chorea, dystonia|
|Ataxia with oculomotor apraxia (AOA) Type 1||9p13.3 APTX (aprataxin gene)||+/−||−||−||Choreoathetosis, hypoalbuminemia, neuropathy, elevated cholesterol and alpha-fetoprotein levels|
|Ataxia with oculomotor apraxia (AOA) Type 2||9q34 SETX gene||+||SWJ, GEN||−||−||Cerebellar atrophy, extrapyramidal features, neuropathy, elevated alpha-fetoprotein levels|
|Friedreich ataxia||9q13–q21.113 with GAA repeats (frataxin gene)||+/−||Near normal saccadic velocities, SWJ, oscillations (flutter), significant loss of VOR||+/−||−||Neuropathy, myelopathy, cardiomyopathy, diabetes mellitus|
Patients with cerebellar ataxias usually exhibit dysmetria and gait ataxia, with some combination of absent tendon reflexes, defective proprioception, and pyramidal (e.g., spasticity, hyperreflexia, and extensor plantar responses) and extrapyramidal (e.g., dystonia, parkinsonism) signs. Eye movement abnormalities are frequent and include gaze-evoked nystagmus, saccadic dysmetria, square-wave jerks, abnormal smooth pursuit, and inability to suppress the VOR. Saccades may be slow (mainly SCAs 1, 2 (severe), and 7), and in severe cases patients lack voluntary saccades, use head thrusts, and have only preserved reflexive eye movements. The impaired saccades and smooth pursuit have been attributed at least in part to degeneration of neurons in the PPRF and the nucleus reticularis tegmenti pontis (NRTP). Some subtypes (see Table 16.2 ) have optic atrophy associated with progressive acuity, field, and color vision loss (see Chapter 5 ), while others have macular or pigmentary retinal degeneration (see Chapter 4 ). MRI typically shows some combination of cerebellar, pontine, and spinal cord atrophy.
Multiple system atrophy (MSA) . Diseases in this category are sporadic and nonhereditary. They are characterized clinically by autonomic failure (i.e., Shy–Drager syndrome) and either parkinsonism (MSA-P), which is usually levodopa-unresponsive, or cerebellar ataxia (MSA-C). MSA can be difficult to distinguish from other parkinsonian syndromes, and ocular motor findings in MSA including excessive square wave jerks, saccadic dysmetria, impaired VOR suppression, and gaze-evoked nystagmus aid in diagnosis. Positional downbeat nystagmus (pDBN) may also be seen with MSA-C. The pathologic hallmark is neurodegeneration of striatonigral and olivopontocerebellar regions with glial cytoplasmic inclusions formed by fibrilized alpha-synuclein.
Huntington disease . Principle clinical features of this neurodegenerative disease include progressive choreoathetosis, rigidity, and dystonia. The pathologic hallmark is atrophy of the caudate nucleus and putamen. The genetic basis is an abnormal CAG trinucleotide repeat expansion on chromosome 4p16.3.
Saccades that are slow vertically more than horizontally (particularly in patients with young age at onset) and difficulty in initiating saccades, sometimes associated with head thrusts, are the most prominent eye movement deficits. Patients also have increased distractibility and unwanted saccades during attempted fixation as well as square-wave jerks (see Chapter 17 ). Smooth pursuit can also be affected, but to a lesser extent.
Parkinson’s disease (PD) . Parkinson’s disease is the second-most common neurodegenerative disorder following Alzheimer’s disease. Cardinal features, including tremor, bradykinesia, rigidity, and postural instability, are due to dopamine deficiency in striatonigral pathways. The most common eye movement abnormalities in PD include saccadic pursuit in all directions of gaze and hypometric saccades; however, most patients do not exhibit prominent eye movement abnormalities, in contrast to progressive supranuclear palsy. Increased saccade latency is associated with cognitive impairment, which generally occurs later in the disease course. Some of the ocular motility abnormalities are thought to reflect basal ganglia dysfunction and dopamine deficiency, although improvement in eye movement measures with levodopa therapy is inconsistent, whereas with deep brain stimulation of the subthalamic nucleus, more consistent improvement in saccadic latency and gain has been demonstrated.
Corticobasal syndrome . This rare, sporadic, progressive neurodegenerative disease of middle-aged or elderly individuals is characterized by clinical features which suggest both cortical and basal ganglionic dysfunction. These include dementia, levodopa-unresponsive parkinsonism, limb dystonia, ideomotor apraxia, hyperreflexia, cortical sensory loss, focal reflex myoclonus, and “alien limb” phenomena. In the late stages of this disease, a supranuclear gaze paresis in all directions, saccade apraxia with normal saccade velocities, and eyelid opening apraxia (see Chapter 14 ) can be seen. Although the clinical presentation may be confused with progressive supranuclear palsy (PSP), corticobasal syndrome more commonly has asymmetric frontoparietal atrophy on neuroimaging, whereas patients with PSP more typically have midbrain atrophy.
Pharmacologic therapies are largely ineffective. The diagnosis can be confirmed only at autopsy, which typically demonstrates swollen, poorly staining (achromatic) neurons and degeneration of the cortex and substantia nigra.
Gaucher disease . A lysosomal storage disorder, Gaucher disease is caused by decreased enzyme activity of glucocerebrosidase with resulting accumulation of a glycolipid, glucocerebroside, in macrophages. The glucocerebrosidase gene has been mapped to chromosome 1q21–31. Anemia, thrombocytopenia, hepatosplenomegaly, infiltration of bone marrow with abnormal histiocytes, and fracture or aseptic necrosis of bone are common systemic features. In the infantile acute GD2 and later onset subacute GD3 forms, neurologic involvement is also seen, with prominent slow horizontal saccades due to PPRF involvement and a progressive supranuclear horizontal gaze paresis. Compensatory horizontal head thrusts may be seen, and a vertical saccadic palsy may develop late in the disease. Eye movements and head thrusts can mimic congenital ocular motor apraxia, and with attempted horizontal excursions, vertically-directed movements may be seen instead.
Others . Horizontal saccadic failure has also been documented in association with other childhood neurodegenerative diseases such as Krabbe leukodystrophy, Pelizaeus–Merzbacher disease, GM1 gangliosidosis, Refsum disease, and propionic acidemia.
Ocular motor abnormalities as biologic markers . Interest has grown in the detection of abnormal eye movements, which are often subtle, as biologic markers in neuropsychiatric diseases in which abnormal ocular motility is not usually a prominent clinical finding. For instance, patients with Alzheimer’s disease, Huntington disease, or schizophrenia may have abnormal anti-saccades. Smooth pursuit may also be abnormal in these patients and their relatives. These ocular motor abnormalities can offer insight into the abnormal neuronal circuitry and pharmacology of these disorders. However, their detection may require eye movement recordings and are frequently too nonspecific to offer any diagnostic utility. Furthermore, in some cases these abnormalities may be the result of neuropsychotropic medications.
Wernicke’s encephalopathy . This disorder, due to a vitamin B 1 (thiamine) deficiency, is characterized clinically by a triad of eye movement abnormalities, gait ataxia, and encephalopathy. The full triad is present in only a minority of cases. Wernicke’s encephalopathy is seen primarily in alcoholics and other malnourished individuals such as prisoners of war or women with hyperemesis gravidarum. Forced or involuntary starvation, cancer, gastric plication, and chronic renal dialysis are other associated conditions. Because thiamine is required for carbohydrate metabolism, Wernicke’s encephalopathy can also be caused inadvertently in individuals with marginal thiamine stores who are given a carbohydrate (e.g., intravenous glucose) load.
Approximately half of patients with Wernicke’s encephalopathy may have a horizontal or less frequently a vertical conjugate gaze palsy. Horizontal gaze-evoked nystagmus may manifest from dysfunction of the NPH–MVN neural integrator complex. In primary position, vertical nystagmus is most common, may reverse direction with convergence (e.g., up to down or vice versa), and may increase in intensity in the direction of the slow phase, contrary to Alexander’s law. Other ocular motor features include sixth nerve palsy, INO, and hypoactive horizontal VOR. Less frequent neuro-ophthalmic abnormalities include retinal hemorrhages, ptosis, and optic neuropathy.
Neuroimaging shows brainstem, thalamic, and hypothalamic lesions typically in the vicinity of the third and fourth ventricles and aqueduct ( Fig. 16.13 ). Characteristic neuropathologic findings include necrosis of nerves and myelin, hypertrophy and hyperplasia of small blood vessels, and pinpoint hemorrhages. These are typically located symmetrically in the mammillary bodies, superior cerebellar vermis, hypothalamus, thalamus, midbrain, and ocular motor and vestibular nuclei. Gaze abnormalities may be attributed to pathologic lesions affecting the PPRF/sixth nerve nuclei, pretectal area, and periaqueductal gray matter.
Following parenteral administration of 50–100 mg of thiamine in addition to receiving a balanced, high-caloric diet, patients often begin recovering from sixth nerve palsies and gaze deficits within 1–24 hours, and almost always within 1 week. By 1 month these deficits usually resolve. However, many require several weeks for nystagmus, ataxia, and confusion to resolve. The horizontal VOR hypofunction may improve drastically within minutes of intravenous thiamine administration. In addition, some patients develop Korsakoff’s psychosis, characterized by retrograde and anterograde amnesia and confabulation, as long-term sequela.
Leigh syndrome (subacute necrotizing encephalomyelopathy) . Abnormal conjugate and dysconjugate eye movements may be seen in this rare, invariably fatal disorder of young children. Psychomotor delay and hypotonia are typically the first manifestations, usually in the first year of life. Subsequent symptoms include abnormal eye movements, vision loss related to optic atrophy, ataxia, peripheral neuropathy, somnolence, deafness, movement disorders, spasticity, and respiratory difficulties.
MRI characteristically demonstrates high signal lesions in the basal ganglia, thalamus, and brainstem. Pathologically, bilaterally symmetric necrotic lesions extend from the thalamus to the pons, but they also involve the inferior olives and posterior columns. These abnormalities resemble those in Wernicke’s encephalopathy and infantile beriberi.
Several biochemical and genetic defects affecting energy metabolism can lead to Leigh syndrome. The more commonly identified ones are a defect involving the pyruvate dehydrogenase complex, cytochrome oxidase deficiency, a T-to-G mutation at nucleotide 8993 in the mitochondrial deoxyribonucleic acid (mtDNA) gene encoding ATPase 6 (the same mutation as in NARP syndrome; see Chapter 4 ), and complex I deficiency. Treatment in most cases is unsatisfactory.
Vitamin E deficiency . There are three major causes of vitamin E (alpha-tocopherol) deficiency: (1) abetalipoproteinemia (Bassen–Kornzweig disease), in which patients lack apolipoprotein B, which is essential for transporting fat-soluble vitamins; (2) malabsorption, due either to cholestatic liver disease with resultant failure to secrete bile, cystic fibrosis, or bowel resection; and (3) familial isolated (autosomal recessive) vitamin E deficiency. Slow saccades may be a feature of the first two causes, but not usually of the familial type. Some exhibit dissociated eye movements, with slow but full abduction of one eye and fast but limited adduction of the other in attempted lateral gaze. Ocular motor palsies and a pigmentary retinopathy may also be observed. Neurologically, patients with vitamin E deficiency may develop ataxia, long tract signs, proprioceptive loss, and areflexia, mimicking Friedreich ataxia.
In suspected cases, serum vitamin E levels should be tested. In many instances vitamin E supplementation may halt or reverse the progression of ocular motor and neurologic symptoms.
Drugs . Table 16.3 lists a number of drugs, even at therapeutic doses, that may impair eye movements.
|Drug||Decreased Saccadic Velocity||Impaired Smooth Pursuits||Internuclear Ophthalmoplegia||Gaze Palsy||Oculogyric Crisis|
|Phenothiazines||+ (Haloperidol)||+||+ (1st>2nd/3rd generation)|
|Other||Gabapentin||Beta-blocker, tacrolimus||Baclofen, valproic acid||Lamotrigine, metoclopramide, cefixime, gabapentin, tetrabenazine, cetirizine, antimalarials|
Abnormal Horizontal Conjugate Gaze Deviations
Supratentorial . Acutely following a supratentorial infarction or hemorrhage, the eyes may be conjugately deviated ipsilaterally toward the lesion ( Figs. 16.14 and 16.15 ). The eye deviation is often evident on neuroimaging (see Fig. 9.8 ) and is more frequent and persistent with right hemispheric lesions. This gaze deviation usually results either from impairment or neglect of the contralateral visual field or from damage to ipsilateral frontopontine fibers descending from the FEF to the pons. The VOR is typically normal, but in the first few days it may be difficult to elicit.
Contralateral gaze deviation is much less common, and may be due to thalamic (see later discussion), putaminal, or frontoparietal hemorrhages although massive ischemic hemispheric strokes may also be responsible. Possible mechanisms include involvement or mass effect in the mesencephalon upon frontopontine fibers after they have crossed in the rostral midbrain, supported by the fact that wrong-way deviation is often delayed by days after the insult (this could correspond with evolving edema, and downward eye deviation from pretectal syndrome may also be seen), irritative effects on the descending fibers (see later discussion), or an interhemispheric smooth pursuit imbalance. The prognosis is generally poor in this population.
Infratentorial . Unilateral pontine disturbances affecting the PPRF or sixth nerve nucleus may result in a contralateral gaze preference and ipsilateral gaze paresis (see Fig. 16.14 ). As mentioned earlier, lateral medullary lesions may produce an ipsilateral gaze deviation. However, patients with lateral medullary lesions usually have full contralateral gaze and hypometric contralateral saccades.
Ictal head and eye deviation are usually contralateral to a cortical seizure focus (see Figs. 16.14 and 16.16 ). The diagnosis is usually obvious when there is hemibody twitching or loss of consciousness if the seizure activity generalizes. The gaze deviation may be nystagmoid, with a contralateral fast component followed by a slow drift of the eyes back toward the midline.
Thalamic hemorrhages, which are usually the result of long-standing hypertension, are suggested by the sudden onset of headache and contralateral hemisensory loss and hemiparesis. Large hemorrhages in this area can cause both horizontal and vertical eye deviations (see later discussion). Patients with severe hemianopia or neglect may exhibit an ipsilateral gaze preference. Contralateral saccades may be hypometric, and ipsilateral pursuit may be defective. Occasionally the eyes may deviate away from the hemorrhage and toward the hemiparesis in so-called “wrong-way eyes” (discussed earlier).
Periodic Alternating Gaze
This disorder is related to periodic alternating nystagmus (see Chapter 17 ) and consists of cycles of conjugate horizontal gaze deviation with compensatory contralateral head turning for 1–2 minutes, followed by a 10–15 second transition period with the eyes and head straight ahead, then subsequent gaze deviation to the opposite side with compensatory head turning for another 1–2 minutes. The eye deviation may be overcome by the VOR. Nystagmus may be seen but is intermittent and not a major feature. Patients are typically awake, although the pattern may be seen in comatose patients.
In general, this motility pattern localizes to the posterior fossa. Reported underlying congenital conditions include hypoplasia of the cerebellar vermis (as in Dandy–Walker malformation and Joubert syndrome (see Chapter 17 )), Arnold–Chiari malformations (downward cerebellar tonsillar herniation), occipital encephalocele, spinocerebellar degeneration, and schizencephaly with optic nerve hypoplasia. Acquired etiologies such as pontine damage, a medulloblastoma, and hepatic encephalopathy have been described.
Like periodic alternating nystagmus, period alternating gaze may reflect damage to the cerebellar inferior vermis, including the uvula and nodulus.
Ping-pong gaze . Also called short-cycle periodic alternating gaze deviation, this ocular motility pattern has horizontal oscillation cycles of only 2.5–8 seconds. The patient appears as if they are watching a ping-pong match. The side-to-side movements are usually smooth and sinusoidal, but a saccadic form has also been described.
Ping-pong gaze is almost always seen in comatose or stuporous patients but implies the brainstem, especially the pons, is relatively intact. The responsible lesions are thought to disconnect the pontine gaze centers from cortical influences, which may hypothetically release vestibular generators. This concept is supported by the fact that awake patients may have ping-pong gaze that is apparent only with fixation removed. The lesions are typically rostral midbrain-thalamic, bilateral basal ganglia, or bilateral hemispheric. Cases associated with a cerebellar vermis hemorrhage and bilateral cerebral peduncle infarctions have been reported.
Vertical Conjugate Gaze: Neuroanatomy
Crucial supranuclear structures mediating vertical gaze are located in the midbrain at the level of the pretectum ( Figs. 16.17 and 16.18 ) . This term refers to the area in the midbrain immediately rostral to the tectum, another designation for the superior and inferior colliculi. The pretectum is also just rostral to the level of the third nerve and red nuclei. The two most important pretectal areas are the riMLF and inC.