Ординатура / Офтальмология / Английские материалы / Imaging of Orbital and Visual Pathway Pathology_Muller-Forell_2005

Neuro-ophthalmology: A Short Primer

Table 3.2. Classes of visual agnosias after Kandel and Wurtz (2000). BA, Brodmann area

3.2.3.1

The Dorsal Pathway

From layer 4B of the primary visual cortex, magnocellular information is transmitted to cells in the thick stripes of V2 as well as to cells inV5,which is located in the monkey-homologue areas of the middle temporal (MT) and the medial superior temporal area (MST) at the intersection of Brodmann areas 19, 37, and 39. In

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addition, the thick stripes of V2 project onto V5 as well (Figs. 3.4, 3.12). These pathways and regions establish the first step of higher-order cortical processing of target motion in three-dimensional space (depth) and extraction of optic flow as well as heading of egomotion in the dorsal pathway (Lisberger et al. 1987; Richer et al. 1991; Watson et al. 1993; Morrone et al. 1995; Cheng et al. 1995; Hotson and Anand 1999;

Previc et al. 2000; Kourtzi and Kanwisher 2000;

Malmgren et al. 2001). Together with information from V4 via the posterior inferior temporal area (PIT) and lateral intraparietal area (LIP),the output is routed to the parietal lobe, in particular the superior parietal lobule (Brodmann areas 5 and 7) (Merigan and Maunsell 1993). These parietal regions compute the visuo-motor transformation, which is necessary to change the retinotopic frame of reference used by the visual areas into a suitable frame of reference for motor commands (Goldberg et al. 1990; Barash et al.1991a,b; Duhamel et al.1992; Andersen et al.1992, 1993, 1998; Colby et al. 1993; Jeannerod et al. 1995;

Andersen 1995, 1997; Caminiti et al. 1996; Rushworth et al. 1998; Duhamel et al. 1998; Burnod et al. 1999; Colby and Goldberg 1999; Kusunoki et al. 2000; Xing and Andersen 2000; Snyder et al. 2000). Finally, these signals are projected onto premotor and motor cortical areas.In particular,signals to the frontal eye fields (FEF, Brodmann area 6 in humans; Petit et al. 1997), the supplementary eye fields (SEF, Brodmann area 6) and the dorsolateral prefrontal cortex (DLPC, Brodmann area 46) are used to generate gaze-shifting eye movements (see below) (Fig. 3.15).

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3.2.3.2

The Ventral Pathway

From blobs and interblob regions,parvocellular information is transmitted to V2 cells in the thin stripes and interstripe regions, respectively (Fig. 3.12). This pathway establishes the first step in higher-order cortical processing of object features such as form and color. In particular, many cells respond to both actual and illusory contours, indicating that they carry out the next step in the increasing abstraction from simple line elements to meaningful objects (Figs. 3.13, 3.14) (von der Heydt et al. 1984; Peterhans and von der Heydt 1993). Subsequently, signals pass via V4 to the inferior temporal cortex (IT), which executes such complex tasks as recognition of faces and other complex and colored objects (Desimone et al. 1985;

Desimone and Schein 1987; Hasselmo et al. 1989;

Rolls 1992; Allison et al. 1994; Kapur et al. 1995;

Sams et al. 1997; Gauthier et al. 1997; Faillenot et al. 1997, 1999; Dolan et al. 1997; Watanabe et al. 1999; Bar and Biederman 1999; Shen et al. 1999).

3.2.4

The Accessory Optic System

The accessory optic system is located in the midbrain rostral to the superior colliculus and receives visual input directly from the retinal ganglion cells as well as from cortical areas V1, V2, and V5 (Telkes et al. 2000; Distler and Hoffmann 2001). For the most part, this phylogenetically old system subserves the optokinetic reflex (see below).

3.3

Eye Movements

The paramount goal of the optomotor system is to keep the fovea, the most sensitive part of the retina, on the selected target of interest despite various possible visual and vestibular disturbances (Fig. 3.1). Six distinctly different control systems have emerged to accomplish the chore. They employ two principal classes of gaze control mechanisms (Glimcher 1999;

Goldberg 2000):

•Reflex gaze-stabilization mechanisms

–Vestibulo-ocular eye movements counteract brief head movements (acceleration domain) and are driven by the vestibular system (vestibulo-ocular reflex,VOR).

U. Schwarz

–Optokinetic-ocular eye movements counteract sustained head movements (velocity domain) and are driven by the visual system (optokinetic reflex, OKR).

•Intentional gaze-shifting mechanisms

–Saccadic eye movements rapidly shift the fovea from one object to another across the visual background.

–Smooth pursuit eye movements keep the fovea on a moving target along its complex 3-dimen- sional trajectory through the visual surroundings.

–Vergence eye movements, which only evolved in binocular vertebrates, add a signal to all other eye movements to differentially move each eye if the point of fixation changes in depth.

–Fixation freezes the eye at a given position for intent gaze and intense observation and actively suppresses all other eye movements.

Except for vergence, all eye movements are conjugate, i.e., both eyes move the same amount in the same direction. Vergence movements, on the other hand, are disconjugate.

Although each of the six different eye movement systems employs a distinctly different premotor neural circuit for gaze control, they all share a final pathway with a common set of supranuclear structures for synchronizing motor output, motoneurons, and muscles.

A multitude of peripheral and central neurological disorders result in characteristic disturbances of the optomotor system (Miller and Newman 1997; Huber and Kömpf 1998; Leigh and Zee 1999). Careful clinical examination of eye movements (Fig. 3.16) usually reveals the site of the lesion very accurately and often is superior to neuroradiological imaging, as many lesions are localized infratentorial in the mesencephalon, pons, or cerebellum.

3.3.1

The Oculomotor Nuclei

and the Extraocular Muscles

Each eye is moved by six extraocular muscles arranged in three antagonistic pairs that rotate it like a globe within the socket of its orbit (Fig. 3.17). The muscles themselves are controlled by three cranial nerves. It is the task of elaborate premotor control circuits within the brainstem and cerebellum to compute the final motor signal for each eye muscle, by weighting and integrating the requests for a change in eye position from all possible visual, vestibular, and

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U. Schwarz

•Intorsion (negative torsional according to the right-hand-rule) rotates the top of the eye toward the nose

•Extorsion (positive torsional) rotates the top of the eye away from the nose.

IV IV

Torsional movements do not change the line of sight and become apparent only in extreme pathological processes (see trochlear nerve palsy below) (Goldberg 2000).

Fig. 3.17. Primary pulling direction of the extraocular muscles. Together, the superior rectus and inferior oblique muscles elevate the eyes from their mid-position, whereas the inferior rectus and superior oblique muscles lower them. In addition, the oblique muscles rotate the eyes inand outward (torsion). R, rectus muscles; O, oblique muscles

proprioceptive sources, and distribute them through the medial longitudinal fasciculus to each oculomotor nucleus (Fig. 3.2). Once the signals reach the oculomotor nuclei, the eye movement cannot be stopped. The nuclear motor command signals must comprise both a dynamic and a static component to move and hold the eye in an eccentric position since extraocular muscles act like a system of springs that tend to keep the eyeball in a central position in its socket. Characteristically, each motor signal consists of a brief, transient burst of spikes (pulse), to overcome viscous resistance and accelerate the eye, and a sustained discharge level (step) that is linearly dependent on the eccentricity and maintained as long as the eye is kept in its new position (Fig. 3.18). This continuing neuronal and, consequently, steady muscular activity is necessary to counteract the restoring spring tensions of the eye muscles (Robinson 1964, 1970, 1973; Robinson et al. 1969; Fuchs and Luschei

1970; Robinson and Keller 1972; Skavenski and Robinson 1973; Glimcher 1999).

Three axes of rotation that intersect at the center of the eyeball define the orientation of the eye:

•Horizontal: yaw

•Vertical: pitch

•Torsional: roll

Possible movements are (Fig. 3.17):

•Abduction: rotates the eye away from the nose

•Adduction: rotates the eye toward the nose in the horizontal plane

•Elevation: rotates the eye upward in the vertical plane

•Depression: rotates the eye downward in the vertical plane

3.3.1.1

Anatomy of the Ocular Motor Nuclei and Nerves

All ocular motor nuclei are located in the midline of the brain stem ventral to the aqueduct of Sylvius and fourth ventricle and close to the medial longitudinal fasciculus and reticular formation. Both the oculomotor (III) and trochlear (IV) nerves lie within the mesencephalon close to the ponto-mesencephalic junction, and the abducens nerve (VI) is situated in the lower pons close to the ponto-medullary junction (Fig. 3.19). For a comprehensive review, see

Buttner-Ennever (1988), Leigh and Zee (1999).

3.3.1.1.1

The Oculomotor Nerve (III)

The oculomotor nucleus lies at the ventral border of the periaqueductal gray matter and extends rostrally to the level of the posterior commissure and caudally to the trochlear nucleus (Fig. 3.19). Its efferent fibers innervate the external medial rectus, superior and inferior rectus, the inferior oblique muscle (see Fig. 3.17), and the levator palpebrae superioris (Buttner-Ennever 1988; Leigh and

Zee 1999). All projections from the oculomotor nucleus are ipsilateral except for those to the superior rectus muscle, which is completely crossed, and to the levator palpebrae superioris, which are both crossed and uncrossed (Horn et al. 1999, 2000). In addition, the nerve carries parasympathetic fibers to the ciliary muscle and the sphincter pupillae subserving control of lens accommodation, pupillary diameter, and choroidal blood flow. These fibers originate from the single Edinger-Westphal nucleus, which is part of the autonomic nervous system and forms the top of the ocular nucleus (Marinkoviç et al. 1989; Kimura 1991; Gamlin and Reiner 1991;

Trimarchi 1992; Klooster and Vrensen 1998;

Donzelli et al. 1998). The fascicles of the oculomotor nerve pass ventrally through the medial longitudinal fasciculus, the red nucleus, the substantia

nigra, and the medial part of the cerebral peduncle. Recent investigations revealed a topographic organization from lateral to medial in the following order: inferior oblique, superior rectus, medial rectus and levator palpebrae, inferior rectus, and pupil (Castro et al. 1990; Gauntt et al. 1995). The rootlets of the third nerve emerge from the interpeduncular fossa and fuse to a single trunk, which passes through the basal cistern between the posterior cerebral artery and superior cerebellar artery (Marinkoviç and Gibo 1994). It runs lateral to the communicating artery below the uncus of the temporal lobe over the petroclinoid ligament medial to the trochlear nerve and lateral to the posterior clinoid process. The blood supply for the intracranial segment of the oculomotor nerve originates from thalamoperforating branches.As the oculomotor nerve leaves the dura, it lies close to the free edge of the tentorium cerebelli. In the cavernous sinus, it runs above the trochlear nerve and receives sympathetic fibers from the carotid artery (Marinkoviç et al. 2001). Leaving the cavernous sinus, it is crossed superiorly by the trochlear and abducens nerves, and divides into a superior and inferior ramus, which pass through the superior orbital fissure into

Fig. 3.19. Diagram of important supranuclear and nuclear brainstem structures that control eye movements. Afferent, visual, and vestibular signals from the superior colliculus (sC) and the vestibular nuclei (NV), respectively, as well as signals from the paramedian pontine reticular formation (PPRF) and mesencephalic reticular formation (MRF) are distributed via the medial longitudinal fasciculus (MLF), which ends in the rostral interstitial nucleus (riMLF). Together with portions of the nucleus reticularis tegmenti pontis (nrtp), the PPRF generates ipsilateral, horizontal saccades, while the riMLF generates vertical and torsional saccades. In addition, the interstitial nucleus of Cajal (yellow circle in the MRF) plays an important role in maintaining the eccentric (vertical) eye position after saccade. Other structures mediate cortical signals for smooth pursuit eye movements to the cerebellum (dorsolateral pontine nucleus, dlpn), or are part of the ‘neural integrator’, in particular, the prepositus hypoglossi nucleus (ppH), which provides the step component of the final signal to the oculomotor nuclei. Cbl, cerebellum; III, oculomotor nucleus; IV, trochlear nucleus; VI, abducens nucleus

the orbit of the eye (annulus of Zinn) (Natori and Rhoton 1994, 1995). The medial rectus, inferior rectus, and inferior oblique muscles are supplied by the inferior ramus of the oculomotor nerve, which branches in the posterior orbit,whereas the superior oculomotor ramus that runs lateral to the optic nerve and ophthalmic artery supplies the superior rectus and levator palpebrae superioris muscles.

It should be mentioned that the levator palpebrae superioris muscle and the pupil have additional sympathetic innervation, which reaches the eye via a different, clinically important route: Preganglionic fibersoriginatefromnucleiwithintheintermediolateral column of the upper thoracic spinal cord, leave the cord with the first thoracic root, run to the apex of the pleura to synapse in the superior cervical ganglion. Postganglionic fibers run with the carotid artery and join the ophthalmic branch of the trigeminal nerve at its entrance into the orbit (Goldberg 2000).

3.3.1.1.2

The Trochlear Nerve (IV)

The trochlear nucleus lies at the ventral border of the central, periaqueductal gray matter, dorsal to the medial longitudinal fasciculus, at the level of the inferior colliculus (Leigh and Zee 1999) (Fig. 3.19). Its axons innervate the contralateral superior oblique muscle (see Fig. 3.17). The fibers pass caudally and dorsolaterally around the central gray matter and cross at the roof of the aqueduct. The nerve emerges dorsally from the brainstem caudal to the inferior colliculus and in close proximity to the tentorium cerebelli. It runs laterally around the upper portion of the pons between the superior cerebellar and posterior cerebral arteries into the prepontine cistern. Within the cistern, the trochlear nerve receives its blood supply from branches of the superior cerebellar artery (Marinkoviç et al. 1996). After penetrating the dura at the tentorial attachment, the nerve enters the cavernous sinus where it runs below the oculomotor nerve and above the ophthalmic division of the facial nerve. Crossing over the oculomotor nerve, the trochlear nerve enters the superior orbital fissure above the annulus of Zinn, passes along the medial part of the orbit, and supplies the superior oblique muscle (Natori and Rhoton 1994, 1995).

3.3.1.1.3

The Abducens Nerve (VI)

The abducens nucleus is located in the lower pons in the floor of the fourth ventricle and is covered by

the genu of the facial nerve (Leigh and Zee 1999) (Fig. 3.19). It contains motoneurons that supply the lateral rectus muscle (see Fig. 3.17) and internuclear neurons. The axons of these cells cross the midline and pass through the contralateral medial longitudinal fasciculus to supply motoneurons of the medial rectus muscle in the contralateral oculomotor nucleus. The abducens nucleus, therefore, is a part of the ocular plant as well as the supranuclear ocular control and constitutes the primary generator for horizontal conjugate eye movements. Fibers to the lateral rectus muscle pass ventrally, laterally, and caudally through the pontine tegmentum and medial lemniscus to leave at the caudal aspect of the pons close to the anterior inferior cerebellar artery. The nerve runs through the prepontine cistern along the clivus and close to the inferior petrosal sinus. It penetrates the dura at the petrous crest medial to the trigeminal nerve, and passes under the petroclinoid ligament into Dorello’s canal (Umansky et al. 1991, 1992). In the cavernous sinus, the abducens nerve lies lateral to the internal carotid artery and medial to the ophthalmic division of the trigeminal nerve (Marinkoviç et al.1994).Finally,the abducens nerve enters the orbit via the superior orbital fissure, runs through the annulus of Zinn, and supplies the lateral rectus muscle (Natori and Rhoton 1995).

3.3.1.2

Lesions of the Extraocular Nuclei and Nerves

The hallmark of (acute) lesions of the extraocular muscles or their supplying nerves is double vision (diplopia) unless the patient was amblyopic, because the object’s image no longer lies on corresponding locations on the retinae. Table 3.3 lists important diseases of the extraocular muscles and neuromuscular junction, which must be excluded carefully due to the therapeutic consequences. Figure 3.20 depicts the main clinical findings for isolated nerve palsies. Table 3.4 lists important etiologies of ocular nerve lesions according to anatomical localizations. However, infratentorial, space-occupying, or ischemic lesions in the brainstem or its proximity rarely cause isolated ocular nerve palsies. Often, they affect multiple cranial nerves and are accompanied by other neurological findings including loss of supranuclear optomotor functions (see below) (Figs.3.21–3.23).For an extensive review, see Miller and Newman (1997), Huber and Kömpf (1998), Leigh and Zee (1999).

Neuro-ophthalmology: A Short Primer

Table 3.3. Important differential diagnosis of extraocular eye muscle paresis (Leigh and Zee 1999; Schwarz et al. 2000)

Strabismus concomitants Vergence spasm

Brain stem lesions with supranuclear oculomotor involvement:

internuclear ophthalmoplegia (INO) skew deviation

Disorders of the neuromuscular junction: myasthenia gravis

Lambert-Eaton myasthenic syndrome botulism

Myopathy:

chronic progressive external ophthalmoplegia (CPEO) mitochondrial cytopathy

Kearns-Sayre syndrome MELAS

mitochondrial encephalopathy lactic acidosis

stroke myotonic dystrophy

oculopharyngeal dystrophy myotubular myopathy inflammation

Endocrine ophthalmoparesis:

M. Basedow

Congenital aplasia/hypoplasia of extraocular muscles Restrictive ophthalmopathy

Tumor of the orbit: metastasis lymphoma pseudotumor

Trauma:

blowout fracture of the orbit

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3.3.1.2.1 Oculomotor Palsy

A lesion of the oculomotor nerve results in a loss of adduction (with crossed diplopia) and upward movements, while downward movements are partially intact due to the superior trochlear muscle (trochlear nerve). The eye has a characteristic resting position that is ‘down and out’ (Leigh and Zee 1999). Furthermore, since eyelid elevation, accommodation, and pupillary constriction are governed by the oculomotor nerve, complete (i.e., internal and external) damage also results in drooping of the eye (ptosis), blurred vision mainly for near objects, and pupillary dilatation (mydriasis) (Fig. 3.20). Incomplete, external lesions, however, are more common (Guy et al. 1985; Trobe 1986; Carlow 1989). In addition, brainstem lesions, e.g., cavernomas, may cause selective loss of oculomotor nerve or nucleus functions (Fig. 3.24).

Important components of the differential diagnosis of the oculomotor palsy include the ophthalmoplegic aneurysm and sequels of the internal carotid, communicans posterior, or posterior cerebral artery (Vukov 1975; Roman and Edwards 1979; Hamer

1982; Guy et al. 1985; Bartleson et al. 1986; Boccardo et al. 1986; Moorthy et al. 1989; Guy and

Day 1989; Fujiwara et al. 1989; DiMario and Rorke

1992; Ranganadham et al. 1992; Striph 1993;

Varma and Miller 1994; Leng et al. 1994; Dehaene

1994; Keane 1996; Tiffin et al. 1996; Kasner et al.

I V

V I

Fig. 3.20. Eye position and direction of diplopia due to isolated palsies of the right oculomotor, trochlear, and abducens nerve (modified after Schwarz et al. 2000). A complete, internal and external palsy of the oculomotor nerve causes additional ptosis and

mydriasis. A trochlear palsy causes a conspicuous

B ie ls c h o w s k y t esspto n t a n e o u s

head tilt towards the unaffected side to compensate for the lack of inversion by the superior oblique muscle. Note the position of the horizontal eye axis shown for each head position. Diplopia is worse after tilting the head in the opposite direction (positive Bielschowsky test). See text for further explanations. III, oculomotor nerve; IV, trochlear nerve; VI, abducens nerve

a

c

c

b

Fig. 3.22a-c. A 51-year-old man with right NIII and bilateral NVI paresis. Diagnosis: plexus papilloma of the fourth ventricle. MRI: a Midsagittal T2-weighted image showing a tumor occupying the entire fourth ventricle. The apparently solid tumor part with irregular signal intensity is surrounded by a CSF-equivalent signal, while a ventral cyst depresses and infiltrates the rhombencephalon. Note ventral depression of the cerebellar vermis and the flow void in the aqueduct. b Corresponding T1-weighted native image showing the intraventricular location of the solid tumor part. Note widening of the roof of the fourth ventricle with open aqueduct, better seen than in the T2-weighted image. c Axial T1-weighted, contrastenhanced view, demonstrating homogeneous signal enhancement of the solid tumor part. The cyst should not be mistaken for the fourth ventricle of which the remnant is seen posteriorly (white arrow). (With permission of Dr. Müller-Forell, Institute of Neuroradiology, Medical School, Mainz)

Fig. 3.23a-d. A 20-year-old man with acute left-sided NIII paresis and right hemiparesis. Diagnosis: tegmental cavernoma. CT: a Axial native view with slightly calcified hyperdense focus in the medial left cerebral peduncle. MR: b Corresponding T2-weighted view with characteristic hypointensity of hemosiderin deposit/calcification and