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

1997; Cawley et al. 1998; Dayan and Elston 1999; Silva et al. 1999; Birchall et al. 1999), and the (rare) ophthalmoplegic migraine, especially in children (Raymond et al. 1977; Troost 1996).

3.3.1.2.2 Trochlear Palsy

An isolated lesion of the trochlear nerve results in deficits in extorsion and depression, causing hypertropia of the affected eye (Bixenman 1981; Brazis 1993; Leigh and Zee 1999). Due to the deviation, the perception of slant is disturbed, and the patient typically complains that horizontal lines will be slanted with respect to each other (reading, descending stairs) (Sanfilippo 1973; Guyton 1988). Therefore, a common finding is head tilt away from the lesion in order to compensate for the misalignment

(Fig. 3.20), and the most reliable clinical test is the head-tilt test (Bielschowsky’s test), where the hypertropia and resultant slant misalignment are maximized as the head is tilted toward the side of the lesion. It should be noted that in a patient with skew deviation (as part of a central [vestibular] disorder), the head-tilt test is usually negative (Vanooteghem et al. 1992; Leigh and Zee 1999). Since this nerve is the longest and thinnest of the cranial nerves, it is particularly susceptible to traumatic damage (Sydnor et al. 1982).

3.3.1.2.3 Abducens Palsy

The abducens palsy is the most common ocular motor paralysis (Leigh and Zee 1999). A lesion of this nerve results in loss of abduction beyond the midline

(with uncrossed diplopia) (Figs. 3.20, 3.25). Typically, patients will have less double vision when looking at a nearby object, because convergence adducts each eye. A nuclear lesion will cause conjugate horizontal gaze palsy, due to the internuclear neurons that run into the medial longitudinal fasciculus (Meienberg and Muri 1992), and very often a peripheral paresis of the facial nerve due to its anatomical proximity.

3.3.2

Supranuclear Synchronization of Eye Movements

In order to attain the appropriate combination of conjugate and vergence eye movements, all six oculo-

motor nuclei are interconnected via the medial longitudinal fasciculus (MLF) (Figs. 3.2, 3.19). This gen- eral-purpose data path travels dorsally in the pons to the rostral interstitial nucleus of the MLF (riMLF), which is located in the mesencephalic reticular formation (MRF), and conveys signals for horizontal, vertical, and torsional gaze (Buttner-Ennever

1988; Buttner-Ennever et al. 1989; ButtnerEnnever and Horn 1997; Leigh and Zee 1999;

Horn et al. 1999):

•For horizontal gaze, it carries axons from the abducens internuclear neurons, which mediate conjugate eye movement commands, to the medial rectus motoneurons in the contralateral oculomotor nucleus. The abducens nucleus itself is considered the horizontal gaze center, as it receives

Neuro-ophthalmology: A Short Primer

commands for slow and fast horizontal eye movements from all sources. Its motor neurons project directly to the ipsilateral lateral rectus muscle.

•For vertical gaze, it carries axons which mediate signals for vestibuloand otolith-ocular reflexes, smooth pursuit, and gaze holding from the vestibular nuclei to the oculomotor and trochlear nuclei as well as the interstitial nucleus of Cajal (inC).

Lesions of the medial longitudinal fasciculus disconnect the motoneurons projecting to the medial rectus muscle from the horizontal gaze center, which results in the well-known clinical entity of an internuclear ophthalmoplegia (INO):

•Ipsilateral supranuclear paresis during conjugate horizontal adduction

•Normal behavior during vergence-induced adduction

•Contralateral abduction nystagmus in the lateral rectus muscle, which is due to a slight compensatory increase in the activity of its projecting abducens motoneurons.

INOs are most often encountered in patients with multiple sclerosis (Fig. 3.26). Table 3.5 summarizes other important etiologies (Anderson 1992; Al-Din et al. 1994; Najim et al.1994; Steinlin et al.1995; Verhagen et al. 1996; Komaba et al. 1997; Galindo et al. 1998;

Constantoyannis et al. 1998; Dalmau and PortaEtessam 2000; Kumar et al. 2000; Eggenberger et al. 2000; Cassidy et al. 2000).

85

Table 3.5. Important etiologies of internuclear ophthalmoplegia (INO) (Leigh and Zee 1999; Schwarz et al. 2000)

Demyelinization: multiple sclerosis postirradiation

Brainstem infarction: syphilis (vasculitis)

Infection: meningoencephalitis syphilis (meningitis)

Space-occupying lesion: subdural hematoma

hydrocephalus/syringobulbia Arnold-Chiari malformation

supratentorial arteriovenous malformation neoplasia

brain stem/fourth ventricle infiltration

paraneoplastic syndrome Degenerative disorder:

progressive supranuclear palsy (PSP) Steele-Richardson-Olszewski syndrome

Nutritional disorder:

Wernicke’s encephalopathy pernicious anemia

Metabolic disorder:

hepatic encephalopathy Fabry’s disease abetalipoproteinemia

Intoxication (selection): barbiturate lithium phenothiazine propranolol

tricyclic antidepressants Trauma:

cervical hyperextension Pseudo-internuclear ophthalmoplegia:

myasthenia gravis Miller Fisher syndrome

d a y

t e y

M L F

86

This well understood clinical picture might be complicated, e.g., in one-and-a-half syndrome, if the underlying process affects other structures, e.g., oculomotor nuclei, its nerve rootlets, or brainstem centers for the generation of saccades.

Furthermore, due to the particular arrangement of the blood supply to the cerebellum with the superior cerebellar arteries and the anterior and posterior inferior cerebellar arteries as well as the brainstem with short and long perforating arteries that emerge from the basilar artery, the infratentorial optomotor system is often involved in ischemic strokes (Fig. 3.27). Several unique and easily recognized clinical entities are known (Table 3.6) (Wall et al. 1986; Bogousslavsky and Meienberg 1987; Liu et al. 1992; Bassetti et al. 1996; Johkura et al. 1998).

a

b

Fig. 3.27a,b. A 61-year-old man with sudden onset of double vision; on neurological examination an internuclear ophthalmoplegia (INO) of the right eye was found. Diagnosis: acute infarction of the left brainstem. MRI: a Axial T2-weighted (TSE) view with hyperintense area of the left peduncle, reaching the aqueduct. b Corresponding DWI image, confirming the diagnosis. (With permission of Dr. Müller-Forell, Institute of Neuroradiology, Medical School, Mainz)

U. Schwarz

Table 3.6. Important midbrain (Liu et al. 1992; Miller and Newman 1997) and ponto-medullary syndromes that involve optomotor structures. c, contralateral; i, ipsilateral

superior cerebellar peduncle cerebral peduncle

Parinaud’s syndrome dorsal midbrain

Nothnagel’s syndrome (1879) +/- oculomotor nerve

fascicle

dorsal midbrain

paramedian midbrain

3.3.3

Gaze Holding Mechanisms

3.3.3.1

The Vestibulo-ocular Reflex

The vestibular system senses head movements and – with a very short latency (<20 ms) – elicits extraordinarily precise, compensatory eye movements in the opposite direction in order to stabilize the gaze: the vestibulo-ocular reflex (VOR). The vestibular labyrinth is composed of several parts that detect both angular and linear motion (Fig. 3.28). Each of the three semicircular canals, that are oriented coarsely at 90º to one other, responds to angular acceleration, while the otolith organs (utricle and saccule) respond to linear acceleration (including gravity).

Rotation of a semicircular canal deflects the cupula due to the inertia of the endolymph, a watery fluid filling the thin membranous tube. The gelatinous cupula is a part of the crista in the ampulla enclosing the hair cells, which consist of several stereocilia and one kinocilium. The hair cells transduce the mechanical shearing into neural impulses (Correia et al. 1996). They react optimally to forces applied in one direction: Deflection of the stereocilia towards the kinocilium causes depolarization, hence, increase in firing frequency of the vestibular nerve, and hyperpolarization otherwise (Leigh and Zee 1999). Linear accelerations of the head,on the other hand,stimulate hair cells of the macula of the utricle (aligned with

the horizontal plane) and saccule (aligned with the parasagittal plane). These hair cells are also embedded in a gelatinous mass. However, additional calcium carbonate crystals (otoconia) are attached on top of the membrane. Altogether, the layout of these hair cells with their directional tuning allows accurate representation of any 3-dimensional head movement in the central nervous system as well as the sense of the subjective ‘upright’.

The blood supply of the labyrinth derives from the labyrinthine artery that usually arises from the anterior inferior cerebellar artery and rarely directly from the basilar artery (Fig. 3.29) (Mazzoni 1972; Leigh and Zee 1999). At the labyrinth, the labyrinthine artery branches into several smaller arteries (Fig. 3.30). Occlusion may cause selective loss of labyrinthine functions and/or deafness (Grad and Baloh 1989; Oas and Baloh 1992).

Nerves from the cristae and maculae reach Scarpa’s ganglion. The vestibular nerve itself is divided into the superior division, which runs with the facial nerve and innervates the anterior and lateral canals and the utricle, and the inferior division, which runs with the cochlear nerve and innervates the posterior canal and the saccule. From Scarpa’s ganglion, the vestibular nerve traverses the cerebellopontine angle below the facial nerve and enters the brainstem between the inferior cerebellar peduncle and the spinal portion of the trigeminal tract (Leigh and Zee 1999). Finally, vestibular afferents synapse on neurons in one of the four vestibular nuclei on each side.

A

P

tea l

l C SSa r

o

2 5

A

a

a

u

s

c

L

a

P

VI

VI

cochlearramus

posterior

vestibular

vestibulo-cochlear

artery

artery

superiorcerebelarartery

basilarartery

labyrinthineartery

anteriorinferiorcerebelarartery

posteriorinferiorcerebelarartery

L

P

arteriesof

thecanals

Fig. 3.29. Arterial blood supply of the brainstem and cerebellum (modified after Fig. 3.40; Nieuwenhuys et al. 1988). Only major branches are labeled

Fig. 3.30. Arterial blood supply of the labyrinth (from Schuknecht 1974). Occlusion of terminal branches may affect single semicircular canals, the utricle, the saccule, and/or the cochlea and cause distinct peripheral vestibular and/or auditory pathologies (see Fig. 3.28 for labels)

Due to their dynamic properties, the canals have already performed a first integration from acceleration to velocity. Hence, in their operational range, the firing frequency of vestibular afferents is roughly proportional to head velocity (Dickman and Correia 1989a,b, 1992; Angelaki et al. 1995;

Hullar and Minor 1999; Hess and Angelaki

1999). These velocity signals are transmitted immediately via a so-called direct pathway from the vestibular nuclei to the extraocular muscles, which are aligned in pairs, with corresponding pairs of canals, and most likely account for the dynamic component of the VOR (Scudder and Fuchs 1992). However, in order to maintain eye position after cessation of the head movement, the labyrinthine velocity signal must be integrated once more: A copy of the velocity signal is fed into an additional premotor neural integrator (especially the cerebellum and the prep-

ositus nucleus of the hypoglossal nerve), which adds a position signal to the velocity signal (Raphan et al. 1979; Cannon and Robinson 1987; Anastasio 1991;

Hain and Zee 1992).

In addition, the vestibular cerebellum (flocculus, nodulus and uvula, dorsal vermis, fastigial nucleus, and uncinate fasciculus) continuously monitors the performance of the VOR as well as its integration with other eye movement generators (e.g.,fixation suppression or smooth pursuit) and is the main source for repair of lesions in the peripheral vestibular system as well as adjustment of the VOR due to changes of the visual input (e.g., wearing new eyeglasses or after eye surgery) (Schwarz 1976; Miles and Lisberger

1981; Waespe and Cohen 1983; Lisberger et al.1984;

Galiana 1986; Suarez et al. 1992; Lewis and Zee

1993; Ito 1993; Solomon and Cohen 1994; Baloh et al. 1997; Belton and McCrea 1999, 2000).

Acute unilateral lesions in the peripheral vestibular system (labyrinth, vestibular nerve, and its brainstem entry zone) (Leigh and Zee 1999) are incapacitating and typically cause (Biedert et al. 1985; Ojala and Palo 1991; Baloh and Jacobson 1996; Hotson and Baloh 1998; Baloh 1998a; Schwarz et al. 2000;

Strupp and Arbusow 2001):

•Vertigo: the illusion of movement of self or the environment

•Nausea and vomitus

•Imbalance and falls

•Spontaneous nystagmus (see below)

•Oscillopsia: the illusion of jerky movements of the environment

•Loss of caloric response

and often include otolith signs and symptoms (Figs. 3.31–3.33) (Aoki et al.1999; Bohmer 1999; Vibert et al. 1999; Vibert and Hausler 2000; Tilikete et al. 2001).

•Ocular tilt reaction: skew deviation, counter rolling of the eyes, head tilt

•Tilt of subjective visual vertical as well as

•Deafness.

See Table 3.7 for important etiologies. The patient’s history together with additional neurological findings supplies the key information to differentiate acute and chronic peripheral and central vestibular disorders (Fig. 3.34) (Brandt and Dieterich 1993, 2000;

Dieterich and Brandt 1993; Baloh 1998b).

0ms

VOR

<20ms

saccade

300ms

Fig. 3.32. The head impulse test (modified after Schwarz et al. 2000). Unilateral testing of the peripheral vestibular system is performed by the head impulse test. The subject is asked to fixate the nose of the examiner. Under normal circumstances, the VOR counteracts a brief jerk (shown to the left) with a very short latency (<20 ms), which cannot be detected. After loss of the VOR due to a lesion in the vestibular labyrinth or nerve, the eyes initially move together with the head. The patient must elicit a saccade to gaze back to the examiner’s nose, which has an easily detectable delay of several hundred milliseconds

Neuro-ophthalmology: A Short Primer

Table 3.7. Important etiologies of vertigo (Leigh and Zee 1999; Schwarz et al. 2000)

Benign paroxysmal positional vertigo (BPPV)a,b

Acute unilateral partial lesion of the vestibular nervea labyrinthitis

vestibular neuritis

Ménière syndromea

Basilar migrainea

Multiple sclerosis a,b

Epilepsya

Posttraumatic vertigo

Other focal lesions or diseases ischemic/hemorrhagic infarcta

labyrinth/vestibular nerve: anterior inferior cerebellar a. s(AICA)

ponto-cerebellar: posterior inferior cerebelli a. (PICA)b

Wallenberg syndrome venous congestiona

hyperviscosity syndrome Valsalva induceda

Arnold-Chiari malformationb

viraler infect of labyrinth/vestibular nerve herpes zoster

bacterial infect of labyrinths/vestibular nerve tuberculoses

spirochetal infect of labyrinths/vestibular nerve syphilis

Lyme disease tumor

vestibular nerve acoustic neurinoma neurofibromatosis II

cerebellopontineb glomus tumor

autoimmune diseasea Cogan syndrome I Susac’s syndrome

degeneration of hair cells otosclerosisa

perilymph fistulaa

congenital anomaly of labyrinth

Drug-induced vertigo anti-vertiginous medication (!) antihypertensives antidepressants

sedatives antiepileptics

Physiologic vertigo motion sickness a,b height vertigo a,b

aRecurrent vertigo

bPositionally induced or enhanced vertigo

91

a

b

c

Fig. 3.34a-c. A 60-year-old man with unspecific vision disturbances, balance disorder, gaze nystagmus to the left, and chronic headache. Diagnosis: hemangioblastoma. MRI: a Axial T2-weighted view at the level of the inferior cerebellum with a primarily cystic formation and a more solid part located at the periphery (arrow). b Corresponding T1-weighted, contrastenhanced image showing homogeneous,strong signal enhancement of the solid tumor part. c Midsagittal T1-weighted, con- trast-enhanced view, demonstrating intraparenchymal location of the tumor in the inferior cerebellar vermis.Although the exit of the fourth ventricle is compressed, CSF circulation continues to be compensated by gentle widening of the aqueduct and third ventricle. (With permission of Dr. Müller-Forell, Institute of Neuroradiology, Medical School, Mainz)

92

3.3.3.2

The Optokinetic Reflex

For simple geometrical reasons, head and eye movements cause apparent motion of the visual surroundings on the retina (retinal slip) (Schwarz and Ilg 1999), and sustained self-rotation in the light causes a compelling sensation (circularvection) despite the lack of peripheral vestibular stimulation (Leigh and Zee 1999).The optokinetic system extracts this global pattern and generates compensatory eye movements to annihilate the disturbing slip and quickly stabilize the visual world on the retina. Hence, this optokinetic reflex (OKR) – supported by the smooth pursuit system (see below) – acts as a visual counterpart to the VOR and enhances the purely vestibular response substantially in the low-frequency range. Together, the vestibulo-ocular and optokinetic systems attain an almost perfect retinal stabilization across a wide range of head movements.

Visual information subserving the OKR travels from the retina directly to the accessory optic system in the pretectum, a midbrain area located rostral to the superior colliculus (Mai 1978; Fredericks et al. 1988; Hoffmann 1996). Both velocity and direction of the retinal slip are extracted by pretectal neurons (Hoffmann and Distler 1989), which themselves

U. Schwarz

project to the vestibular nuclei via pontine and medullary pathways (Buttner-Ennever 1988; Fuchs and Mustari 1993; Wallman 1993). Furthermore, the convergence of visual and vestibular signals upon central vestibular neurons suggests a common final pathway for gaze-holding eye movements (Henn et al. 1974; Glimcher 1999).

Deterioration of the OKR, especially a reduction in velocity, occurs in a variety of diseases, notably in multiple sclerosis (Todd et al. 2001), and often is accompanied by malfunctioning of the central vestibular system.

3.3.3.3 Nystagmus

Nystagmus denotes a rapid involuntary oscillation of the eyes, which typically consists of a slow phase followed by a quick resetting saccade. Traditionally, the direction of the nystagmus is determined by the quick phase. Both the direction and velocity of the slow component are determined either by a physiological stimulus or the site of the lesion within the oculomotor system. Figure 3.35 shows the generation of a pathological vestibular nystagmus due to a labyrinthine lesion. It should be noted, however, that

eye

position

apparentegomotion

X

t im e

Fig.3.35.Development of a unidirectional spontaneous nystagmus (modified after Schwarz et al. 2000). Acute loss of the neuronal resting discharge in the left labyrinth (X) is equivalent to a head movement to the right (see Fig. 3.31), as the drive of the optomotor system and perception of ego-motion only depends on the difference between the vestibular inputs from both sides. Accordingly, the optomotor system generates an eye movement to the left (VOR, slow phase), which periodically is interrupted by a resetting saccade (fast phase) if the eye position exceeds a certain limit. Altogether, these jerky back-and-forth movements of the eyes constitute a nystagmus. Its direction is defined by the direction of the saccade and is independent of the eye position