Ординатура / Офтальмология / Английские материалы / The Neurology of Eye Movements_Leigh, Zee_2006

changed by convergence.1041'1268 Thus, in some patients with acquired pendular nystagmus63 or central vestibular forms of nystagmus (downbeat, upbeat, torsional), convergence variably suppresses, increases, or changes the form of the oscillations.297'435'1021 Further, congenital nystagmus is often suppressed by convergence, a factor that has therapeutic significance.827

CONVERGENT-DIVERGENT

PENDULAR OSCILLATIONS

This form of nystagmus has been described in patients with multiple sclerosis,64 brain stem stroke,555 and cerebral

Whipple's disease (see VIDEO: "Whipple's disease").1248 In the last case, the abnormal

eye movements have been ascribed to oscillations of the vergence system—hence the term pendular vergence oscillations.1248

This nystagmus typically has a frequency of about 1.0 Hz and is accompanied by concurrent contractions of the masticatory muscles (oculomasticatory myorhythmia). In addition, paralysis of vertical gaze occurs and may mimic the paralysis of progressive supranuclear palsy.881'1119

Using reliable methods of measuring eye movements, other patients have been reported with pendular oscillations that were about 180° out of phase in the horizontal and torsional planes but had conjugate vertical components.64 In certain patients, the torsional oscillations are the greatest in amplitude (cyclovergence nystagmus). The convergent-divergent nature of the nystagmus might be explained in two possible ways: a phase shift between the eyes, produced by dysfunction in the normal yoking mechanisms; or an oscillation affecting the vergence system itself. The latter is a more likely explanation, since studied patients showed no phase shift (i.e., were conjugate) vertically, and the relationship between the horizontal and torsional components was similar to that occurring during normal vergence movements (excyclovergence with horizontal convergence).64 Under experimental conditions, the vergence system has been

made to oscillate at frequencies of up to 2.5 Hz,1158 lower than the frequency re-

ported in patients with conditions other than Whipple's disease. To account for

these higher-frequency oscillations, it seems necessary to postulate instability within the brain stem-cerebellar connections of the vergence system, such as between nucleus reticularis tegmenti pontis and the cerebellar posterior interposed nuclei (discussed in Chap. 8).64

VERTICAL NYSTAGMUS WITH A CONVERGENT-DIVERGENT HORIZONTAL COMPONENT

Like pendular nystagmus, some forms of jerk nystagmus have a convergent or divergent component. For example, the upbeat nystagmus shown in Figure 10-6 in a patient with multiple sclerosis (see VIDEO: "Upbeat nystagmus") has convergent slow phases. Only occasionally are the horizontal, disjunctive components of the nystagmus large enough to be clinically apparent. Divergence nystagmus has been reported with cerebellar diseases such as Arnold-Chiari malformation, when combined divergent and downbeat nystagmus

produces slow phases that are directed upward and inward.264'1509 These forms of

nystagmus might reflect an otolithic imbalance, since geometric factors require that the normal, translational vestibulo-oc- ular reflex (see Fig. 1-5) during vertical (bob) or fore and aft (surge) translational head movements combines conjugate vertical and disconjugate horizontal movements if the subject looks at a near object above or below eye level or off to one side. Future studies of the three-dimensional properties of vertical nystagmus are needed to clarify these issues.

CONVERGENCE-RETRACTION NYSTAGMUS

This is not truly a form of nystagmus, since each cycle of the oscillation is initiated by a disjunctive saccade (or quick phase) that converges and retracts the eyes (see VIDEO: "Convergence-retraction nystagmus"). It is caused by lesions of the mesencephalon that involve the region of the posterior commissure, classically pineal tumors (see Ocular Motor Syndromes Caused by Lesions of the Mesencephalon, below).264'1029 Convergence nystagmus has also been described in patients

with Arnold-Chiari malformation.972 During horizontal saccades, the abnormal pattern of convergent innervation manifests itself as slowing of the abducting eye: pseudo-abducens palsy.*19 Convergenceretraction nystagmus is elicited either by asking the patient to make an upward saccade, or by using a hand-held optokinetic drum or tape, moving the stripes down (see VIDEO: "Convergence-retraction nystagmus"). With the optokinetic stimulus, slow, downward, following eye movements occur, but the upward quick phases are replaced by rapid convergent or retractory movements, or both. Convergence-retrac- tion nystagmus is usually intermittent, being determined by saccadic activity, and so can be differentiated from other, more continuous forms of disjunctive nystagmus such as acquired pendular nystagmus and the oculomasticatory myorhythmia that is characteristic of Whipple's disease. Pretectal pseudobobbing consists of nonrhythmic, rapid movements which carry the eyes down and medially, and which are followed by a slow return to midline; each movement may be preceded by a blink.745 This disorder is reported in patients with acute obstructive hydrocephalus and is probably a variant of convergence nystagmus.

Normal subjects show small, transient disjunctive movements during vertical saccades: often there is convergence with

downward movements and divergence with upward,1529 which is the opposite of

the pattern occurring in convergenceretraction nystagmus (see saccade-vergence interactions, in Chap. 8). Further, the retraction makes it likely that cocontraction of the extraocular muscles is occurring with each saccade. What structure or connections in the dorsal midbrain are responsible for this mis-programing of saccades has yet to be elucidated.

Congenital Forms of Nystagmus

THE NATURE OFCONGENITAL OCULAR OSCILLATIONS

Progress in understanding the pathogenesis of congenital nystagmus has been advanced by the development of an animal

model in normal monkeys that are deprived of binocular vision during early life1400 and the identification of congenital forms of nystagmus in mutant dogs with abnormal anatomy of the visual system.372'373 However, although some patients with congenital nystagmus show visual abnormalities, others with similar ocular oscillations do not. Furthermore, the presence of any one type of wave- form—such as pendular (see Fig. 10-ID) or jerk (Fig. 10-1A)—does not suggest a specific pathogenesis or indicate whether the congenital nystagmus is associated with visual system anomalies.356 Thus, the underlying mechanisms are not fully understood. Three distinct syndromes are currently recognized: congenital nystagmus, latent nystagmus, and spasmus nutans.

CONGENITAL NYSTAGMUS

Clinical Features of Congenital Nystagmus

Congenital nystagmus may be present at birth but usually develops during infancy.537 It occasionally presents during adult life,476'553 when it may create a diagnostic problem, especially if the patient has other symptoms such as headaches or dizziness. Although variable in form, certain clinical features usually differentiate congenital nystagmus from other ocular oscillations (Display 10-11) (see VIDEO: "Congenital nystagmus"). It is almost always conjugate and mainly horizontal, even on up or down gaze. A torsional component to the nystagmus is probably common, but is usually too small to identify clinically.3 Less commonly, congenital nystagmus is mainly seesaw (see VIDEO: "Seesaw nystagmus"), and such patients may have underlying disease of the retina,536'538 visual pathways,40'351 or cerebellum. Con-

genital nystagmus that is conjugately vertical is rare.139'1303

Congenital nystagmus is usually accentuated by the attempt to fixate an object, and by attention or anxiety. Eyelid closure1281 and convergence usually suppress it,386 but occasionally congenital nys-

tagmus is evoked by viewing a near target.1268'1520 Its intensity may also be in-

fluenced by viewing the vertical lines of an optokinetic tape.320 Often, nystagmus decreases when the eyes are moved into a particular position in the orbit; this is called the null point or zone, and corre-

sponds to the range of eye position within which slow-phase eye velocity is at a minimum. In some patients, the nystagmus periodically reverses direction, but this reversal seldom occurs in the regular manner seen in the acquired form of periodic alternating nystagmus.7'356'542 In some patients, the direction of the nystagmus is influenced by which eye isviewing, the nystagmus beating away from the covered eye. This is similar to what happens in latent nystagmus, which is discussed next.

The most distinctive feature of congenital nystagmus is its waveforms; the commonest are increasing-velocity (see Fig. 10-1C) and pendular (Fig. 10-1D). Frequently superimposed on these waveforms, which may be combined, are

foveation periods, the "signature" of congenital nystagmus (Fig. 10-13).U,io8,356,362

During each cycle—usually after a quick

phase—there is a brief period when the eye is still and is pointed at the object of regard. With jerk waveforms, the quick

phases (saccades) may "brake" the oscillation,357 or bring the eye to the target. With

pendular waveforms, the oscillation is "flattened" by a foveation period when the eye is closest to the target (Fig. 10-13B). Foveation periods are probably one reason why most patients with congenital nystagmus do not complain of oscillopsia,

in spite of otherwise nearly continuous movement of their eyes,355'362'523'829 and

why many have normal visual acu- ity.252-1279 Foveation periods are not invari-

able in congenital nystagmus, however. When they are absent or poorly developed, visual acuity is usually impaired.107'362 Foveation periods are only rarely reported in acquired forms of nystagmus, however.355'1314 The waveform also depends upon the child's age, being large-amplitude "triangular" in the first few months of life, then pendular, and fi-

nally jerk as the patient reaches about a year of age.1133 These waveforms are so

characteristic of congenital nystagmus that

444 The Diagnosis of Disorders of Eye Movements

Figure 10-13. Congenital nystagmus. Examples of

(A) horizontaljerk waveform, with slow phases that drift away from the fixation position with increasing velocity waveforms (evident on lower, magnified scale), (see VIDEO: "Congenital nystagmus") and (B) a pendular type of waveform with superimposed quick phases. Note that both subjects show foveation periods, following quick phases, when the eye is close to the desired fixation point and eye velocity is low. POS, position; VEL,velocity.

reliable records of eye position and velocity will often secure the diagnosis.

Up to 30% of patients with congenital nystagmus have strabismus.350 A commonly described associated finding is "inversion of smooth-pursuit or optokinetic responses."576 Thus, with a hand-held optokinetic drum or tape, quick phases are directed in the same direction as the drum rotates. In fact, the phenomenon can be explained in terms of shifts in the position of the null point of the nystagmus induced by the pursuit or optokinetic stimuli. Measurement of tracking during foveation periods has shown that smooth pursuit and optokinetic eye movements are preserved in at least some individuals.369-801 Similarly, the higher-frequency vestibular responses have generally been found to be normal in patients with congenital nystagmus and, if judged from retinal image stability during the foveation period, performance is normal and allows a similar view of the world while the patient is stationary

or in motion.234'370 However, patients with congenital nystagmus may show increased thresholds for motion perception.12583 Especially in those patients with associated visual disorders such as albinism, vestibular responses to lower frequencies of head rotations and optokinetic responses (i.e., the velocity-storage mechanism} may be impaired.379'550 Occasional patients exhibit their congenital nystagmus only during attempted smooth tracking,757 and others can voluntarily release or inhibit their congenital nystagmus, suggesting that the fixation mechanism plays some role in their oscillations.1402 Congenital nystagmus associated with congenital gaze-hold- ing failure (i.e., leaky neural integrator] has been reported in one kindred.371

Head turns are common in congenital nystagmus and are used to bring the eye in the orbit close to the null point or zone, at which nystagmus is minimal. The presence of such head turns in childhood photographs is often useful evidence in diagnosing congenital nystagmus. Another strategy used by patients with either congenital or latent nystagmus is to purposely induce an esotropia (nystagmus blockage syndrome] in order to suppress the nystagmus; such an esotropia requires a head turn to

direct the viewing eye at the object of interest.359'1440

Some patients with congenital nystagmus also show head oscillations.234'358'557'11193

Such head movements could not act as an adaptive strategy to improve vision unless the vestibulo-ocular reflex were negated. In most patients with congenital nystagmus, head movements are not compensatory and tend to increase when the individual attends to an object, an effort that also increases the nystagmus. It seems possible, therefore, that the head tremor and ocular oscillations represent the output of a common neural mechanism.358'11193

Pathogenesis of Congenital Nystagmus

As noted above, nystagmus developing early in life and showing some of the waveform characteristic of congenital nystagmus in humans occurs in mutant dogs

who lack any decussation of their visual pathway,372 as well as in normal monkeys who undergo a form of monocular visual deprivation in infancy.1400 Nystagmus is also associated with a variety of visual system disorders, including ocular and oculocutaneous albinism,5'284'1032 achromatopsia, cone dystrophy, optic nerve hypoplasia, Leber's congenital amaurosis, colobomata, aniridia, corectopia, congenital stationary night-blindness, Chediak-

Higashi syndrome, Joubert's syndrome, and peroxisomal disorders.536'538'1465 Nys-

tagmus that is present at birth, but resolves by 6 months of age, has been associated with delayed visual maturation.130a Failure to develop a normal optic chiasm may predispose to congenital seesaw nystagmus.40 Nystagmus associated with the above-mentioned conditions may not show the classic features of congenital nystagmus. Because of the many diagnostic possibilities, a complete ophthalmologic evaluation and an electroretinogram are necessary in patients with nystagmus asso-

ciated with decreased visual acuity or visual dysfunction.254-528'809'1465 Congenital

nystagmus, either with or without associated visual system abnormalities, may be familial.361'371'762 Several modes of inheritance have been reported; in X-linked forms, the mothers may show subtle ocular motor abnormalities. Congenital nystagmus has been reported in monozygotic twins,4-6 and a gene for an autosomal dominant form has been described.761'762 However, the waveforms or other characteristics of the nystagmus may differ

considerably between twins or other relatives.6'350'361

The known anatomical variations of the anterior visual system in individuals with congenital nystagmus, such as excessive crossing at the chiasm in association with albinism,562'918 or absent crossing of nasal fibers in achiasmatic subjects with congenital seesaw nystagmus,40'372 have led to development of models for congenital nystagmus based on "miswiring" of visual pathways.1047'1402 These ideas about the pathogenesis of congenital nystagmus are discussed further in Chap. 4, under Smooth Pursuit in Patients With Congenital Nystagmus.

LATENT (OCCLUSION) NYSTAGMUS

Clinical Features of

Latent Nystagmus

True latent nystagmus is a jerk nystagmus that is absent when both eyes are viewing but appears when one eye is covered: quick phases of both eyes beat away from the covered eye (Display 10-12) (see VIDEO: "Latent nystagmus"). In most patients, nystagmus (which may be of low amplitude) is present when both eyes are uncovered (manifest latent nystagmus}; however, only one eye is fixating, and vision from the other eye (which may be deviated, e.g., esotropic) is suppressed.365'559 Usually, the nystagmus reverses direction upon covering of either eye; in some patients, nystagmus is present when one particular eye is covered but is absent when the other is occluded. Occasional patients can control their latent nystagmus at will.788 Latent nystagmus is usually associated with strabismus, typically esotropia.366'1235 Amblyopia is frequent, whereas binocular vision with normal stereopsis is rare. Like strabismus, latent nystagmus sometimes occurs in individuals who have no other evidence of neurologic dysfunction, but it is more common in patients with disorders of cerebral development, such as Down's syndrome.53

The slow phase of latent nystagmus shows a linearor decaying-velocity waveform (Fig. 10-1), in contrast to the increas- ing-velocity waveform of congenital nystagmus.559 Recent studies have suggested that foveation may occur during the slowest part of the drift if the amplitude of the nystagmus is large and immediately after the quick phase if the amplitude is small.363'4223 Latent nystagmus usually follows Alexander's law, the nystagmus being greatest on looking in the direction of the quick phases, away from the covered eye. Some patients turn their head to keep their viewing eye in an adducted position, where nystagmus is minimal;784 this and other strategies to reduce latent or congenital nystagmus have been called nystagmus blockage syndrome.S59'l548a Occasionally, congenital and latent nystagmus coexist and the waveforms may be more compli-

cated. Rarely, if vision is clearer with the latent nystagmus waveforms than with the congenital nystagmus waveforms, such patients may switch from congenital to latent nystagmus as one eye becomes esotropic and the other takes up fixation.359 In addition to strabismus, upward deviation of the covered eye (called alternating sursumduction or dissociated vertical deviation) and a torsional component to the nystagmus are frequently associated.35>565a'1415 Individuals with latent nystagmus show asymmetry of monocular smooth pursuit, optokinetic nystagmus, and the cortical visual-evoked response (VEP) to motion stimuli; the significance of these findings is discussed in the next section and under Smooth Pur-

suit, Visual Fixation, and Latent Nystagmus, in Chap. 4.197a'787'1235-1404 Latent nys-

tagmus is quite a common disorder, and accurate diagnosis is important to avoid inappropriate investigations. It should be differentiated from gaze-evoked nystagmus in association with strabismus, and especially from abducting nystagmus occurring with internuclear ophthalmoplegia, in which an exotropia may be present but adducting saccades are slow.

Pathogenesis of Latent Nystagmus

Latent nystagmus can be induced experimentally in monkeys by depriving them of binocular vision early in life, either by patching one eye1400 or by surgically creating strabismus.768 The cortical areas that extract motion information from visual stimuli—such as V5 or area MT (see Fig. 6-8, in Chap. 6)—in such monkeys have normal responses but are rarely driven binocularly.768 Changes are also found in the nucleus of the optic tract (NOT), to which V5 projects, where neurons normally respond to visual stimuli presented to either eye. In monkeys with latent nystagmus, these neurons are driven mainly by the contralateral eye.986 Thus, for example, during monocular viewing through the right eye, the left NOT will be activated preferentially, producing leftward slow phases of nystagmus. Furthermore, inactivation of NOT with muscimol abolishes latent nystagmus in monkeys who have been deprived of binocular vision.986

Latent nystagmus occurs in some, but not all, patients who have congenital uniocular visual loss, suggesting that addi-

tional factors beyond visual deprivation

are responsible for the development of nystagmus.802'1274 Such factors may in-

clude disturbance of directed visual attention or egocentric localization. Thus, some patients can change the direction of their nystagmus by "attempting" to view from one eye or the other, without a change of visual inputs.354-788 It is also possible that abnormality of extraocular proprioception predisposes to latent nystagmus,677 because extraocular proprioception has been shown to be important for the normal development of binocularity.207 Now that animal models have been developed for latent nystagmus, the relative contribution of each of these factors is amenable to investigation.

SPASMUS NUTANS

Clinical Features ofSpasmus Nutans

This disorder is characterized by the triad of nystagmus, head nodding, and anomalous head positions, such as torticollis

(Display 10-13) (see VIDEO: "Spasmus Nutans").1020 Its onset is usually in the first

year of life. Neurologic abnormalities are

absent, although strabismus or amblyopia may coexist.1517 The syndrome is some-

times familial and has been reported in monozygotic twins.660 Spasmus nutans spontaneously remits, usually within 1 to 2 years after onset, although it may persist for over 8 years.539

The most consistent feature of spasmus nutans is the nystagmus, although head

nodding may be the first abnormality to be noticed.539'549'554'1466 The nystagmus is

usually intermittent, small amplitude, and with a high-frequency (3-11 Hz, "shimmering"), pendular waveform; it is easily missed. It may be more evident in the abducting eye during lateral gaze. Characteristically, the nystagmus differs in the two eyes, and sometimes it is uniocular. Another distinguishingfeature of these oscillations is the variability of the amplitude in each eye and the phase relationship between the two eyes. Consequently, even over the course of a few seconds or minutes, the oscillations might variably be conjugate, disconjugate, disjunctive, or purely monocular (Fig. 10-14). The plane of the nystagmus is predominantly hori-

zontal but it may have vertical or torsional components. It may sometimes be brought out by evoking the near response.249

The head nodding is irregular, at a frequency of about 3 Hz, with horizontal or vertical components. It is usually more prominent when the child attempts to inspect something of interest. About twothirds of the patients have an additional head tilt or turn. In some patients, the head nodding appears to turn off the nystagmus.549'554 However, it remains unclear whether head nodding, turning, or tilting is always an adaptive strategy adopted to reduce the nystagmus, or instead reflects the underlying abnormality in spasmus nutans.

Two important clinical judgments have to be made in children with eye and head oscillations. The first judgment is whether the nystagmus reflects a tumor of the optic

nerve, chiasm, retina, or more posterior visual pathways.430'538-808'818 A careful oph-

thalmologic evaluation should be performed in all such children; if there is any doubt about the diagnosis, imaging studies should be performed. The second judgment is whether the child has spasmus nutans, which resolves, or congenital nystagmus, which does not. Spasmus nutans can be differentiated from congenital and latent nystagmus by its intermittency, high frequency, vertical component, and dissociated characteristics; if the child will

cooperate, eye movement records often help make the distinction.1466

Pathogenesis of Spasmus Nutans

The underlying abnormality in spasmus nutans is unknown. Although the ocular oscillations are of high frequency, their disconjugate vertical component makes saccadic oscillations unlikely, since the eyes are tightly yoked during normal vertical saccades. The reported ability of the

active head nodding,549'554 but not passive rotation in a chair,1466 to stop the ocular

oscillations implies the importance of a voluntary effort. Further, affected children are reported to suppress their nystagmus with a head turn, even though changing eye position in the orbit had no effect.251 Thus, voluntary head movements or positions seem essential for returning stability to gaze. Finally, the resolution of spasmus nutans with age might reflect either structural maturation of the nervous system or "full calibration" of eye movements.

LidNystagmus

Reflecting the anatomic and physiological links between vertical eye and lid movements, upward movements of the eyelids frequently accompany upward movements of vertical nystagmus. An important structure in the coordination of vertical saccades is the M-group of neurons, which lies adjacent, medial, and caudal to riMLF (see Fig. 6-3 and Fig. 6-4) and projects to both the elevator subnuclei of the eye (superior rectus and inferior oblique) and the motoneurons of levator palpebrae superi-

oris in the central caudal subnucleus of the oculomotor nucleus.218-219 The M-

group also has reciprocal connections with the nucleus of the posterior commissure. Thus, in patients who have dissociation of lid-eye movement during vertical saccades (i.e., impaired lid saccades in the presence of preserved eye saccades), the M-group or the nucleus of the posterior commissure is likely to be involved. Similarly, lid nystagmus unaccompanied by vertical eye nystagmus may also reflect midbrain lesions.186-202 Patients with longstanding compression of the central caudal nucleus causing "midbrain ptosis" may develop lid nystagmus.186

Twitches of the eyelid may also accompany horizontal nystagmus. This phenomenon has been described in a patient with Wallenberg's syndrome (lateral medullary infarction), in whom lid nystagmus was inhibited by convergence.321 The opposite— eyelid nystagmus that is evoked by convergence (Pick's sign)—is reported with

medullary and cerebellar lesions.657'1202-1213 The association of lid nystagmus with convergence may reflect the normal synkinetic lid retraction that occurs during an effort to view a near target. Thus, convergence effort increases innervation to the lids and so may amplify any lid nystagmus.

Saccadic Intrusions

THE SPECTRUM OF

SACCADIC INTRUSIONS

Several types of inappropriate saccadic movements may intrude upon steady fixation (Display 10-14); these are schematized in Figure 10-15 and actual recorded examples are shown in Figure 10-16. Saccadic intrusions should be differentiated from nystagmus, in which a drift of the eyes from the desired position of gaze is the primary abnormality. They should also be differentiated from saccadic dysmetria (see VIDEO: "Saccadic hypermetria") (Fig. 10-15A), in which the eye overshoots or undershoots, sometimes several times, before landing on target.162'1254 Because saccadic intrusions are rapid and brief, it is usually necessary to measure eye and target position and eye velocity in order to identify accurately the saccadic abnormality. We first describe the characteristics of each type of saccadic intrusion and then consider their mechanisms of pathogenesis.

SQUARE-WAVE JERKS

A common finding in healthy subjects, particularly the elderly, is square-wave jerks, also called Gegenrucke.6l7'lZ5g-l2ei On eye movement records—see Figure 10-15C and Figure 10-16A—they have a profile that earned them their name. They are small, conjugate saccades, ranging from 0.5° to 5.0° in size, which take the eye away from the fixation position and then return it there after a period of about 200 msec. They are often more prominent during smooth pursuit and most easily detected during ophthalmoscopy. They are also present in darkness. In certain cerebellar syndromes,1117 progressive supranu-