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

510 The Diagnosis of Disordersof EyeMovements

Bilateral INO and an associated sixth nerve palsy may mimic the one-and-a halfsyndrome. A case of one-and-a-half syn-

drome has been described in which only adduction in one eye was spared.238 The

patient had mucormycosis that caused a sixth nerve palsy due to cavernous sinus involvement on one side and on the other side had a horizontal gaze palsy due to carotid artery occlusion. Lesions that damage the MLF and ipsilateral abducens fascicle produce horizontal ophthalmoplegia in the ipsilateral eye from the combination of an INO and a sixth nerve palsy. Lesions that damage the MLF on one side and the PPRF or abducens nucleus on the opposite side produce a horizontal gaze palsy toward the same side as the involved PPRF or abducens nucleus. In such cases, the INO cannot be diagnosed because of the overriding horizontal gaze palsy. Damage to the MLF on one side and to the contralateral abducens nerve fascicle will produce abduction weakness of the contralateral eye combined with adduction weakness of the ipsilateral eye. In this setting, there will be a pseudo-horizontal gaze palsy on attempted horizontal gaze away from the side of the MLF lesion. This diagnosis may be suspected in a patient who appears to have a horizontal gaze palsy that is asymmetric, with one eye (usually the adducting eye) being more limited than the other.

Selective Cell Vulnerabilityin

the Pons

Certain metabolic, toxic, and degenerative conditions may cause selective deficits of ocular motility that suggest a predominant loss of one population of brain stem neurons concerned with eye movements. Such a process has been proposed to explain slow saccades and saccadicoscillations.

SLOW SACCADES WITH PONTINE DISEASE

Disorders that are reported to cause slow saccades are listed in Table 10-15. Predominant slowing of horizontal saccades

Table 10-15. Etiology of

Slow Saccades

Spinocerebellar ataxias (SCA), especially

SCA2 (olivopontocerebellar

atrophy)211'643'1039'1151'1220'1443'1485

Huntington's disease286'815'833 Progressive supranuclear palsy1186'1429

Parkinson's (advanced cases)1480 and related diseases;332'1496 Lytico-Bodig854

Whipple's disease776

Lipid storage diseases1187'1247 Wilson's disease770

Drug intoxications: anticonvulsants,1361'1371 benzodiazepines118°

Tetanus932

In dementia: Alzheimer's disease (stimulus-

dependent),465 and in association with AIDS1009

Lesions of the paramedian pontine reticular formation585

Internuclear ophthalmoplegia1533 Paraneoplastic syndromes70'303 Amyotrophic lateral sclerosis (some cases)54

Peripheral nerve palsy, diseases affecting the neuromuscular junction and extraocular muscle, restrictive ophthalmopathy

generally occurs in hereditary degenerative disorders that involve the pons, especially spinocerebellar ataxia type 2 (olivopontocerebellar atrophy of Wadia and

Swami) (see VIDEO: "Slow horizontal saccades").211'1443'1535 As discussed above, al-

though attempts have been made to define the phenotypic disorder of eye movements for each genetically determined disorder, exceptions occur. In diseases that principally affect the midbrain, such as progressive supranuclear palsy (PSP), vertical saccades become slow before horizontal ones do. Selective slowing of horizontal saccades in association with facial spasms has been described as a probable paraneoplastic phenomenon in association with prostatic cancer.70

In some patients with slow horizontal saccades, blinks of the eyelids may actually speed up these movements;1528 the explanation for this phenomenon is uncertain but is more likely to involve the effects of blinks upon pause and burst neurons than

momentary deprivation of vision (see Saccades and Movements of the Eyelids, in Chap. 3). Some patients with slow saccades are able to generate smooth-pursuit movements of up to about 20° per second. It is difficult to distinguish a considerably slowed saccade from pursuit, however, so whether or not pursuit function is truly intact in such patients is not established. Conversely, if the saccades are so slow that they cannot bring the eye to the moving target, then even if pursuit is intact it may not appear so, as the eye appears to lag the target. Vestibular stimulation elicits normal compensatory slow phases, but quick phases of nystagmus are either absent or are slow and show approximately the same abnormal relationship between amplitude and peak velocity as do voluntary saccades. Patients with olivopontocerebellar degeneration usually make nor- mal-amplitude saccades despite their low velocity. Patients with slow saccades may use a variety of strategies of eye-head coordination to move their eyes more quickly to the target (see Eye-Head Movements in Patients With Slow or Inaccurate Saccades, Chap. 7).

The simplest explanation for slow horizontal saccades is that excitatory burst neurons in the PPRF are involved.649 However, experimental lesions of the omnipause neurons using excitoxins are also reported to cause slow horizontal and vertical saccades.718 In some patients with selective slowing of horizontal saccades, both burst and omnipause cell populations may be affected,585 but selective involvement of the excitatory burst neurons has been demonstrated in olivopontocerebellar atrophy of the type described by Wadia and Swami.649 An alternative explanation for saccadic slowing is that it represents abnormal inputs to the paramedian reticular formation. Thus, experimental lesions or pharmacological inactivation of the frontal eye field or superior colliculus causes slowing of saccades (discussed in Chap. 3).

SACCADIC OSCILLATIONS WITH PONTINE LESIONS

Saccadic oscillations that lack any intersaccadic interval (ocular flutter and opso-

clonus—Fig. 10-15E) (see VIDEOS: "Opsoclonus") have been attributed to disease that selectively affects the omnipause neurons,1536 which are located in the nucleus raphe interpositus in the midline of the pons at the level of the abducens nucleus (Fig. 6-2, Chap. 6). However, experimental lesions of the omnipause region with excitotoxin caused slow saccades rather than oscillations.718 Furthermore, neuropathologic examination of the brain of two patients who had manifest opsoclonus as the remote effect of lung cancer did not disclose changes in the omnipause population.1142 A more recent immunopathologic study of a patient with saccadic oscillations in association with cancer did demonstrate complete absence of cells in the omnipause region, however.648 Thus, it remains possible that lesions restricted to omnipause cells may cause saccadic oscillations, but alternative mechanisms are possible, as discussed in the section on saccadic oscillations. Macrosaccadic oscillations (see VIDEO: "Macrosaccadic oscillations") (Fig.lO-16C)—an extreme form of saccadic dysmetria—have been reported with a paramedian lesion involving the tegmentum and basis pontis,55 although it is more usually a feature of cerebellar disease.

OCULAR MOTOR SYNDROMES CAUSED BY LESIONS OF THE MESENCEPHALON

Modern Concepts of Vertical

Gaze Palsies

The midbrain is important in the control of vertical eye movements, especially saccades and gaze holding. Patients with acute palsies of vertical gaze usually have lesions localized to structures lying in the high mesencephalon (Display 10-24). In evaluating the patient with a disturbance of vertical gaze, first it is crucial to test not just range of movement but also to determine whether there are selective defects of saccades or of smooth pursuit, vestibular, or vergence eye movements. Although certain lesions may cause paralysis of

all upward or downward movements, or both, selective defects of ocular motility are more common. Second, it is also important to test the torsional vestibuloocular reflex, noting whether quick phases of nystagmus occur in both directions as the patient's head rolls from side to side. Third, examine ocular alignment, looking for signs of oculomotor or trochlear palsy, and for evidence for skew deviation and the ocular tilt reaction. Fourth, look for abnormalities of eyelid movements and the pupils, which are common features of vertical gaze disorders.

Although human studies have made important contributions to understanding the control of vertical gaze, the value of many older reports is limited either by lack of information concerning the effects of lesions on each class of eye movements or by uncertainty as to the degree of involvement of the important structures for vertical gaze. Over the past 20 years, the pathways critical for vertical gaze have been defined using modern anatomical and physiological techniques, and the be-

havioral deficits that have resulted when such pathways are selectively lesioned have been measured. These experimental studies, which are summarized in Chap. 6, have defined the roles of three key structures in the control of vertical gaze: the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), the interstitial nucleus of Cajal (INC), and the posterior commissure.

Lesions of the riMLF and Vertical Saccadic Palsy

In interpreting vertical saccadic palsies, it is helpful to bear in mind several key facts. The first is the anatomic location of the riMLF (see Display 6-5), which contains the burst neurons that generate vertical and torsional saccades. The riMLF lies dorsomedial to the rostral pole of the red nucleus, medial to the fields of Forel, lateral to the periaqueductal gray and the nucleus of Darkschewitsch, and immediately rostral to the interstitial nucleus of Cajal

(see Fig. 6-3 and Fig. 6-4, Chap. 6). Second, the riMLF receives its blood supply from a small perforating vessel (the posterior thalamosubthalamic paramedian artery) that arises between the bifurcation of the basilar artery and the origin of the posterior communicating artery, with a single vessel often supplying both riMLFs.240'1074 Certain details concerning the projections of the riMLF are clinically relevant. Each riMLF projects bilaterally to motoneurons for the elevator muscles (superior rectus and inferior oblique) but ipsilaterally to motoneurons for the depressor muscles (inferior rectus and superior oblique).966'967 Note that these bilateral projections probably are not achieved via the posterior commissure but occur at the level of the oculomotor and trochlear nuclei. What this means is that unilateral riMLF lesions are more likely to affect downward than upward saccades. Furthermore, each burst neuron in the riMLF sends axon collaterals to motoneurons supplying yoke muscle pairs; this appears to be part of the neural

substrate for Hering's law in the vertical plane.965 Thus, riMLF lesions (unilateral or bilateral) would be expected to cause vertical saccadic defects that are mainly conjugate. A final anatomic point is that although each riMLF contains burst neurons to drive upward or downward saccades, the right riMLF is responsible for torsional quick phases that are clockwise from the point of view of the patient (extorsion of the right eye and intorsion of the left eye), and the left riMLF is responsible for counterclockwise quick phases. Thus, although the effects of a unilateral riMLF lesion on vertical saccades may be minor, it will abolish ipsitorsional quick phases and produce a cyclorotation of both eyes (shift of Listing's plane).

Lesions of the riMLF are usually infarcts in the distribution of the posterior thalamosubthalamic paramedian artery, which may be paired or single, and which may also supply the rostromedial red nucleus, adjacent subthalamus, the poste- rior-inferior portion of the dorsomedial

nucleus and the parafascicular nucleus of the thalamus. Older reports of vertical

gaze disorders have been reviewed in a modern context,214'1080 and here we focus

on recent reports.

Based on experimental studies,1347 a unilateral lesion of the riMLF would be expected to cause a minimal defect in ver-

tical saccades (mainly downward) but a distinct defect in generating ipsitorsional quick phases (Display 10-25). Patients

have been reported with such find- ings.837-1148 They also have a static, con-

tralesional torsional deviation with torsional nystagmusbeating contralesionally.608 Other patients with a unilateral riMLF

lesion have been described as having greater defects of vertical saccades or other eye movements. In the case of Ranalli and colleagues,1123 the infarct had spread partly into the adjacent interstitial nucleus of Cajal; saccades were absent above the central position, and slow and limited below. Smooth pursuit and the vestibulo-ocular reflex were also affected in the vertical plane, being restricted in range and of reduced gain. These additional defects might be attributed to in-

volvement of the interstitial nucleus of Cajal. In another patient who had a discrete, unilateral riMLF lesion associated with bilateral infarction in the base of the pons, there was a vertical saccadic palsy, but other eye movements were spared.148

Bilateral lesions of the riMLF are more common and have been reported to cause loss either of downward saccades (Fig. 10-28) (see VIDEO: "Vertical saccadic palsy") or of all vertical saccades. The explanation for selective paralysis of down-

516 The Diagnosis of Disorders of Eye Movements

ward saccades has centered on which part of the riMLF is affected and how this partial lesion might affect emerging axons from burst neurons for upward or downward saccades.1080 Impairment of vertical smooth pursuit and the vestibulo-ocular reflex probably reflects involvement of adjacent structures such as the MLF and interstitial nucleus of Cajal. Somnolence or memory impairment may imply coexistent involvement of medial thalamic nuclei. A vertical one-and-a-half syndrome has been reported, with either loss of all downward

movements and selective loss of upward movements in one eye346 or impairment of

all upward eye movements and a selective deficit of downward saccades in the eye on the side of the lesion.150 Since each burst neuron in the riMLF sends axon collaterals to yoke muscle pairs, such deficits imply that a lesion close to the motoneurons

of the muscle must be responsible for the disconjugate deficit.

Lesions of the Interstitial Nucleus

of Cajal (INC)

Recent experimental work has demonstrated that the INC (see Display 6-6)

plays a key role in holding eccentric vertical gaze (Display 10-26).298>608b Further-

more, the INC appears to project exclusively to the ocular motoneurons via the posterior commissure (see next section). However, it seems that the defect of vertical gaze associated with INC lesions is not just one of vertical gaze-evoked nystagmus.1066 Bilateral pharmacological inactivation of INC in monkeys greatly restricts the vertical range of all classes of conjugate eye movements, although saccades do

not become slow.608b With these new pieces of information, it is instructive to reexamine how frequently the INC has

been reported as being involved in cases of vertical gaze disturbance.214-1080'1123

While bilateral lesions of INC mainly affect vertical gaze, unilateral lesions produce the ocular tilt reaction and torsional nystagmus with compensatory ipsilesional quick phases (which helps differentiate it

from torsional nystagmus due to riMLF lesions).172a'608

Effects of Lesions of the Posterior

Commissure and Nucleus of the

Posterior Commissure (nPC)

syndrome, Parinaud's syndrome, Koeber- Salus-Elschnig syndrome, pretectal syn-

drome, and Sylvian aqueduct syndrome.319'1067'1069 In the past, paralysis of

upward gaze was ascribed to destruction of the superior colliculi, but this is not the case.21'1068 Unilateral midbrain lesions that create the same ocular motor syndrome may do so by interrupting the afferent

and efferent connections of the posterior commissure.51'214-1123'1300 Experimental in-

activation of the posterior commissure with lidocaine causes vertical gaze-evoked

nystagmus,1066 but electrolytic lesions cause greater deficits (Display 10-27).1067'1069

Thus, it seems that the clinical syndrome associated with posterior commissure lesions is due to more than axon projections of the INC (see Display 6-7) and also represents lesioning the nucleus of the posterior commissure (nPC), which may be important for the control of vertical gaze and eyelid movements. Cells in the nPC project through the posterior commissure to contact the riMLF, INC, and the M-group of neurons; the M-group relays to the central caudal subdivision of the oculomotor nu-

cleus (Fig. 9-9) and may coordinate vertical eye and lid movements.1231

The vertical gaze defect observed with clinical lesions affecting the posterior corn-

Table 10-16. Features of The Dorsal

Midbrain Syndrome2i4,3i9,745,75i)io8o,i379

Limitation of Upward Eye Movements

Saccades

Smooth pursuit

Vestibulo-ocular reflex

Bell's phenomenon

Dissociation of Lid and Eye Movements

Lid Retraction (Collier's Sign)

Ptosis

Disturbances of Downward Eye Movements

Downward gaze preference ("setting sun" sign)

Downbeating nystagmus

Downward saccades and smooth pursuit may be impaired, but vestibular movements are relatively preserved

Disturbances of Vergence Eye Movements

Convergence-retraction nystagmus Paralysis of convergence

Spasm of convergence Paralysis of divergence A- or V-pattern exotropia Pseudo-abducens palsy Pretectal pseudobobbing

Fixation Instability (Square-Wave Jerks)

Skew Deviation

Pupillary Abnormalities (Light-Near Dissociation)

missure usually affects all types of eye movements, though the VOR and Bell's phenomenon may sometimes be spared. Eyelid abnormalities occur: Collier's "tucked lid" sign (or lid retraction),287 or less commonly, ptosis. Below the horizontal meridian, vertical saccades can be made but are usually slow. Acutely, the eyes may be tonically deviated downward

('setting sun sign"); this finding is prominent in premature infants who have suffered intraventricular hemorrhage.1356

Transient downward deviation of the eyes occasionally occurs in normal infants, but, in such cases, the eyes can be easily driven above the horizontal meridian by the vertical doll's-head maneuver.663 Tonic upward gaze deviation of the eyes has been reported in some patients with midbrain

lesions,96 and following hypoxic-ischemic insults.743 Oculogyric crises are discussed under the section on Parkinson's disease. Episodic tonic up gaze may also occur in otherwise normal infants,18 although some may later show horizontal strabismus and intellectual or language disability.598

The dorsal midbrain syndrome also includes disturbance of horizontal eye movements, especially vergence. In some patients, convergence is paralyzed, while in others it is excessive and causes convergence spasm. During horizontal saccades, the abducting eye may move more slowly than its adducting fellow. This finding has been called pseudo-abducens palsy319 and may reflect excess of convergence tone. It may lead to an early symptom of posterior commissure lesions: reading difficulty caused by a transient inability to find, and to focus both eyes on, the beginning of the next line when a horizontal saccade is made. Convergence-retraction nystagmus may also occur following experimental lesions of the posterior commissure1067'1069 and in patients with disease of the midbrain.1029 Convergence-retraction nystagmus is properly regarded as a saccadic disorder since it consists of asynchronous, opposed saccades whenever upward quick phases are stimulated (see VIDEO: "Con- vergence-retraction nystagmus"). Convergence is often evident during attempted large upward movements and contrasts

with the transient divergence that occurs in normal subjects.1529 Pupillary reactions are also commonly affected. Usually, the pupils are large and react better to an accommodative stimulus than to light— light-near dissociation.

A variety of disease processes may affect the region of the posterior commissure and disrupt vertical gaze (Table 10-17 ). Pineal tumors produce the dorsal midbrain syndrome either by direct pressure on the posterior commissure or by causing obstructive hydrocephalus.72 Hydrocephalus may produce this syndrome by enlarging the aqueduct and third ventricle or the suprap-

ineal recess and so stretching or compressing the posterior commissure.294 The fol-

lowing case history illustrates certain features of the dorsal midbrain syndrome.

CASE HISTORY: Vertical gaze palsy with midbrainhemorrhage

A 38-year-old woman presented with a 10-day history of fever, sores in her mouth, bruises, and profound tiredness. Hematological findings were consistent with monocytic leukemia in biastic crisis. One day after admission she became stuporous and developed a right hemiparesis.

On examinationthe left pupil was oval, approximately 5 mm in diameter, and fixed. The right pupil was 3 mm and fully reactive. There was a full range of horizontal eye movements,

but with continuous square-wave jerks during attempted fixation. She had complete paralysis of vertical eye movements above the midline. Below the horizontal meridian, downward pursuit was abnormal and saccades, both up and down, appeared slow. There was a downward beating nystagmus on attempting to look down. Horizontal saccades appeared to be of normal velocity but horizontal pursuit was bilaterally impaired. There was some horizontal gaze-evoked nystagmus.Vergence could not be elicited.

Computed tomography (Fig. 10-29A) demonstrated a hemorrhage in the left mesencephalon. The patient died a few days later. Examination of the brain confirmed the presence of the midbrain hemorrhage with compression and displacement of the aqueduct and the posterior commissure (Fig. 10-29B).

Comment: This patient showed evidence of left oculomotor nerve dysfunction and dorsal

midbrain syndrome. Although CT indicated a unilateral mesencephalic lesion, autopsy showed that the posterior commissure was compressed. Moreover, the hemorrhage was located so as to affect fibers coursing into and out of the posterior commissure. Involvement of the left cerebral peduncle accounted for the right hemiparesis.

Clinical Manifestations of Other

Mesencephalic Lesions

The effects of lesions affecting othermesencephalic structures are less certain. The periaqueductal gray matter of the mesencephalon is known to contain both bursttonic cells and neurons that cease discharge during saccades. Selective loss of down gaze with tonic upward deviation of