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

PMT pathway is discussed further in Cerebellar Influences on Gaze, below.

Interpretation of the Effects of Discrete Lesions on Pathways for Horizontal Gaze

A test of the validity of the anatomic scheme shown in Figure 6-1 is its ability to account for the effects of discrete lesions on horizontal eye movements. Lesions of the abducens nucleus produce paralysis of both the ipsilateral lateral rectus and contralateral medial rectus for all conjugate eye movements (see Display 10-20, Chap.

10).2i,52,i95,209 Vcrgence is spared, since

these movements mainly depend on projections that pass directly to medial rectus motoneurons. Saccadic, pursuit, optokinetic, and vestibular movements are still present in the contralateral hemifield, but are impaired when directed toward the side of the lesion. Contraversive saccades are preserved because they depend on the intact abducens nucleus, which receives projections from excitatory burst neurons in the ipsilateral PPRF. Saccades directed toward the side of the lesion are also present in the contralateral hemifield of movement, but they are slow. This is because they must now depend solely on projections to the intact abducens nucleus from

the inhibitory burst neurons of the contralateral medullary reticular formation, and saccadic peak velocity is now a function of antagonist muscle relaxation rather than agonist contraction. Another finding with abducens nerve palsies is horizontal gaze-evoked nystagmus on looking contralaterally. This nystagmus is probably due to involvement of fibers of passage from the medial vestibular nucleus, which provide an eye position signal to the contralateral abducens nucleus.209 This explanation is supported by the report of a discrete experimental lesion made between the abducens nuclei, which caused profound bilateral gaze-holding failure.3 Alternatively, it might be due to involvement of the PMT cell group that lies at the rostral pole of the abducens nucleus and possibly

contributes to horizontal gaze-holding via its projections to the cerebellum.47'209

Lesions of the medial longitudinal fasciculus produce internuclear ophthalmoplegia (INO) (see Display 10-22, Chap. 10), which is characterized by paresis of adduction for conjugate movements on the side of the lesion (see VIDEO: "Unilateral internuclear ophthalmoplegia").54'85'100 Adduction is still possible with convergence because of direct vergence inputs to medial rectus motoneurons (see Fig. 6-1; VIDEO: "Bilateral internuclear ophthalmoplegia"). Thus, when INO is produced experimentally by lidocaine blockade of the MLF between the levels of the trochlear and abducens nuclei, the vergence response is preserved or even increased.100 More rostral lesions of the MLF may impair vergence if the medial rectus motoneurons or their vergence inputs are involved. With complete, experimental lesions of the MLF, the eye does not adduct across the midline with any conjugate movements, implying that extra-MLF pathways, such as the ascending tract of Deiters, can only play a minor role in the horizontal VOR. A combined lesion of one MLF and the abducens nucleus on the same side produces paralysis of all conjugate movements save for abduction of the eye contralateral to the side of the lesion; this is

known as one-and-a-half syndrome (see Display 10-23).90'250

Discrete lesions of the paramedian pontine reticular formation (PPRF) cause loss of saccades and quick phases of nystagmus

to the side of the lesion (see Display 10-21).108'161 Experimental lesions in the

PPRF, using excitotoxins that spare fibers of passage, leave smooth pursuit, the vestibulo-ocular reflex, and gaze-holding ability intact;125 similar sparing is sometimes encountered with clinical lesions.118-161 Often, however, lesions of the pons that affect the PPRF also involve axons conveying vestibular and pursuit inputs to the abducens nucleus.252 Furthermore, lesions that affect the excitatory burst neurons may also affect omnipause neurons, which lie in the nucleus raphe interpositus, close

to the midline at the level of the abducens nerve (Fig. 6-2),42>142'230 and which inhibit

all burst neurons except during saccades. Involvement of omnipause neurons might account for the slowing of vertical as well as horizontal saccades that is sometimes reported after bilateral pontine lesions.118'125

Unilateral lesions affecting the vestibular nuclei, such as in Wallenberg's syndrome (lateral medullary infarction) (see Display 10-16), may produce an ocular motor imbalance manifest by spontaneous nystagmus, skew deviation and the ocular tilt reaction. An additional finding, lateropulsion of saccades (see VIDEO: "Wallenberg's syndrome"), may reflect interruption of axons running in the restiform body from the inferior olivary nucleus to the cerebellum.340 Bilateral, experimental lesions of the nucleus prepositus hypoglos- si-medial vestibular complex, the NPHMVN region, abolish the gaze-holding mechanism (neural integrator) for eye movements in the horizontal plane.49'197

BRAIN STEM CONNECTIONS FOR VERTICAL AND TORSIONAL MOVEMENTS

The ocular motoneurons concerned with vertical and torsional eye movements lie in the oculomotor nucleus and trochlear nucleus. How do these motoneurons receive signals for each functional class of eye movement? A partial dichotomy is evi-

dent, with vertical saccadic commands and gaze-holding (neural integrator) innervation being generated in the midbrain, and vestibular and pursuit signals arising from the lower brain stem.

Vertical and torsional saccades are generated in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), a region of the rostral mesencephalon in the prerubral fields, rostral to the tractus retroflexus and caudal to the mammil-

lothalamic tract (see Display 6-5, Fig. 6-3, and Fig. 6-4).38'40'139 In the past, this struc-

jacent to other mesencephalic reticular nuclei, particularly the interstitial nucleus of Cajal, its physiologic properties and

anatomic connections make it a distinct functional entity. It contains both excitatory and inhibitory burst neurons for

vertical and torsional saccades and quick phases.37'206,208,2i7 Each riMLF contains

neurons that burst for upward and downward eye movements, but for torsional quick phases in only one direction. Thus, the right riMLF discharges for quick

phases that are directed clockwise with respect to the subject;37'38'155'337 that is, the

top pole of the right eye rotates temporally, and the top pole of the left eye rotates nasally. Electrophysiologic and anatomic studies suggest that although excitatory and inhibitory burst units are intermingled, neurons projecting to muscles that depress the eye (inferior rectus and superior oblique) may be located more

rostrally, whereas projections to muscles that elevate the eye (superior rectus and inferior oblique) lie more caudally.163'344 The postulated projections of the riMLF and the associated neurotransmitters are summarized in Figure 6-5. Each riMLF projects predominantly to the ipsilateral oculomotor and trochlear nuclei; however, projections to motoneurons innervating the elevator muscles appear to be bilateral, with axon collaterals probably crossing to the opposite side at the level of the motoneurons, and not in the posterior commissure.207 Furthermore, each burst neuron in the riMLF appears to send axon collaterals to motoneurons supplying yoke muscle pairs; this appears to be part of the neural substrate for Hering's law of equal innervation in the vertical plane.202'205 Axons from the riMLF neurons also send collaterals to the interstitial nucleus of Cajal (bilaterally for upward burst neurons) and to the PMT cell groups,47 which project to the cerebellum. The riMLF receives an as-

cending projection from omnipause neurons in the pons.218

Unilateral, experimental lesions of the riMLF using excitotoxins that spare fibers of passage cause a mild defect in vertical movements, consisting of slowing of downward saccades (see Display 10-25).318 This slowing probably occurs because each nucleus contains burst neurons for both upward and downward movements; however projections to motoneurons innervating depression are ipsilateral, whereas those innervating the elevators may be bilateral.207 At the same time, a severe, specific defect of torsional quick phases is produced.318 For example, with a lesion of the right riMLF, torsional quick phases clockwise from the point of view of the subject (extorsion of the right eye and intorsion of the left eye) are lost; in addition, there is a static, contralesional torsional deviation (equivalent to a shift of Listing's plane), with torsional nystagmus beating contralesionally.123 Similarly, a lesion of the left riMLF impairs counterclockwise quick phases. Unilateral riMLF lesions in humans are reported to produce similar but generally more severe defects, probably because of involvement of adjacent structures.176 Bilateral experimental lesions of

the riMLF in monkeys abolish vertical and torsional saccades,318 but vertical gazeholding, vestibular eye movements, and pursuit are preserved, as are horizontal saccades. Patients with discrete, bilateral infarction in the region of the riMLF show deficits of either downward saccades (see VIDEO: "Vertical saccadic palsy") or both upward and downward saccades.40'249

A critical structure for vertical gazeholding (the neural integrator) is the interstitial nucleus of Cajal (INC) (Display 6-6). This nucleus contains at least two distinct populations of neurons.357 In the monkey, some neurons in the INC encode the complete, vertical, burst-tonic, ocular motor signal.156 The INC receives inputs from the vestibular nuclei, y-group, and axon collaterals from burst neurons in the riMLF.158'159 Pharmacological inactivation of the INC with muscimol causes impaired vertical and torsional gaze-holding after a saccade carries the eye to a tertiary (oblique) position.68-69 The gaze-holding signal following a vestibular eye movement may also depend on ascending signals from the nucleus prepositus hypoglossi. The INC projects to vertical motoneurons in the oculomotor and trochlear subnuclei on the contralateral side of the brain stem

via the posterior commissure (Display 6-7).159 Experimental inactivation of the

posterior commissure with lidocaine causes failure of vertical gaze-holding function, with centripetal drifts of the eyes following vertical saccades.237 Larger destructive lesions severely limit vertical eye movements, especially upward;240'241 it is possible that such lesions also affect other structures, such as the nucleus of the posterior commissure, which normally contribute to upward gaze.

The INC also contains neurons that project to motoneurons of the neck and trunk muscles and appears to coordinate combined eye-head movements in torsional and vertical planes. Stimulation near the INC in the monkey produces an ocular tilt reaction (see Fig. 10-18) that consists of an ipsilateral head tilt and a synkinetic ocular reaction: depression and extorsion of the eye ipsilateral to the stimulation and elevation and intorsion of the contralateral eye;346 similar findings have

been reported in a human patient.180 Experimental, unilateral lesions of the INC also cause an ocular tilt reaction with contmlateral head tilt, skew deviation with hypertropia of the ipsilateral eye, extorsion of the contralateral eye, and intorsion of

the ipsilateral eye. This pattern of ocular tilt reaction is similar to that produced by stimulation of the contralateral utricular nerve317 and is encountered clinically with a variety of brain stem lesions that involve central otolithic pathways.28 Bilateral inac-

tivation or lesions of INC restrict the vertical ocular motor range, and cause upbeat nystagmus and neck retroflexion.97>123a

The neural signals necessary for vertical vestibular and smooth pursuit eye movements and for contributions to the vertical gaze-holding command ascend from the medulla and pons to the midbrain. The MLF is the most important route for these projections, but the brachium conjunctivum (superior cerebellar peduncle) and other pathways are also involved. Details of ascending vestibular projections are

summarized in Figure 2-3 and Table 2-2 in Chapter 2. The ascending axons concerned with vertical eye movements arise from vestibular nucleus neurons that have been calledposition-vestibular-pause cells.326'353

They carry an eye position signal and a head velocity signal and cease discharging during vertical saccades. These fibers also convey an eye velocity signal during vertical smooth pursuit, but during combined eye-head tracking (see Chap. 7), when the eyes may be nearly stationary in the orbits, a head velocity signal is still present on

these axons. This vestibular signal must be canceled by another equal and opposite signal, which also projects to the oculomotor and trochlear nuclei. One mechanism that might make possible such cancellation of the VOR during vertical eye-head tracking is a gaze velocity signal that ascends from the dorsal portion of the y-group (Display 6-8), a small collection of

cells that cap the inferior cerebellar peduncle.51>59'238,239,282,307 Tne y-group re-

ceives afferents from flocculus Purkinje cells and projects to the oculomotor and trochlear nuclei via the brachium conjunctivum and a crossing ventral tegmental tract.

Consistent with these projections is the finding that bilateral lesions of the medial longitudinal fasciculus cause bilateral INO and impair vertical vestibular and smooth-

pursuit movements, but they spare vertical saccades (see Display 10-22).85'266 In

addition, partial loss of the vertical eye position signal causes vertical gaze-evoked nystagmus. Other cell groups in the mesencephalon may contribute to the control of vertical gaze. The nucleus of the posterior commissure (nPC) contains neurons that burst for upward saccades206'207 and project through the posterior commissure to contact the riMLF, INC, and the intralaminar thalamic nuclei.39 The central mesencephalic reticular formation (cMRF)

(Display 6-9), which contains the nucleus subcuneiformis, seems to play an important role in the control of horizontal and vertical saccades.62'117'342 It receives inputs from the PPRF, nucleus of the posterior commissure, fastigial nucleus, and cortical eye fields, and has reciprocal connections with the superior colliculus. Its other projections are to the omnipause neurons and nucleus reticularis tegmenti pontis (NRTP).61'117'342 Experimental lesions of the cMRF cause hypermetria of contralateral and upward saccades and hypometria of ipsilateral and downward saccades.341 In addition, fixation is disrupted by saccadic intrusions directed away from the side of inactivation (see Display 10-28). The periaqueductal gray matter is known to contain neurons with vertical bursttonic or saccadic pause properties.149 An important structure in the coordination of vertical saccades and eyelid movements is the M-group of neurons, which lie adjacent, medial, and caudal to the riMLF and project to both the elevator subnuclei of the eye (superior rectus and inferior oblique) and the motoneurons of the levator palpebrae superioris in the central

caudal subdivision of the oculomotor nu- cleus.44-48'292 The M-group also has recip-

rocal connections with the nucleus of the posterior commissure, and lesions affecting either structure may disrupt lid-eye

coordination during vertical saccades.48 The nucleus of Darkschewitsch does not seem to be involved in the control of eye movements.39

CEREBELLAR INFLUENCES ON GAZE

The cerebellum (Fig. 6-6) optimizes eye movements so that they are calibrated to ensure clearest vision. Two main subdivisions of the cerebellum play an important role in the control of eye movements: (1) the vestibulocerebellum (flocculus, paraflocculus, nodulus, and ventral uvula), and

(2) the dorsal vermis of the posterior lobe and the fastigial nucleus.

Contributions of the

Vestibulocerebellum to

Gaze Control

Theflocculi are paired structures which, in human brain, lie adjacent to the tonsils (paraflocculi), ventral to the inferior cerebellar peduncle, and next to the eighth cranial nerve (Display 6-10). In primates,

the caudal five folia of the flocculus receive mossy fiber inputs mainly from the vestibular nucleus and nerve, the nucleus prepositus hypoglossi (NPH), the nucleus reticularis tegmenti pontis, and the mesencephalic reticular formation. The adja-

cent paraflocculi receive inputs mainly from the contralateral pontine nuclei. Both the flocculi and paraflocculi receive climbing fiber inputs from the contralateral inferior olivary nucleus (Fig. 6-1), which might provide information impor-

tant for adaptive ocular motor con- trol.i7,io5,i68,2i5,223a Qn the basis of this pat-

tern of inputs, it is suggested that the flocculus is more important for controlling the vestibulo-ocular reflex, whereas the paraflocculus mainly contributes to smooth pursuit.215

One further important input to theflocculus is from the cell groups of the paramedian tracts (PMT), which receive inputs from essentially all premotor structures that project to ocular motoneurons (Display 6-4).43>47 The PMT cell groups are, numerically, a larger projection to the flocculus than are the vestibular nuclei, but only recently have they been defined and studied. One PMT cell group in the medulla, the nucleus pararaphales, receives

inputs from the INC and projects via the ventrolateral surface of the medulla and inferior cerebellar peduncle to the flocculus and ventral paraflocculus.43 Neurons in another probable PMT cell group, the nucleus incertus, have been shown to contain burst-tonic neurons,58 and so it seems

possible that the PMT cell groups send an efference copy of eye movement commands to the flocculus.47 Such a signal could be important for normal function of the gaze-holding (neural integrator) network or for the adaptive control of eye movements. The main efferent pathways