ABSTRACT
A. Components 1. Retina, retinal nerve fiber layer, optic nerves, optic
chiasm, optic tracts, lateral geniculate bodies, optic radiations, and visual cortices (Fig. 3-1)
B. Retina 1. Extends from ora serrata to optic nerve (Fig. 3-2) 2. Divided into four quadrants by the macula
a. Vertical meridian: separates superior and inferior retina b. Horizontal meridian: separates nasal and temporal retina
3. Retina layers (Fig. 3-3) a. Retinal pigment epithelium
1) Deepest layer of retina 2) Forms outer blood-retinal barrier and supports
photoreceptors physiologically b. Photoreceptor layer
1) First neural elements in the retina to react to light 2) Rod and cone cells contain light-sensitive pigment
rhodopsin 3) Photoreceptors hyperpolarize (membrane potential
becomes more negative) in presence of light 4) Rod cells are sensitive to low levels of light
a) Minimal role in color vision (except blue spectrum) b) Rods are concentrated in peripheral retina c) No rods within the macula
5) Cone cells respond to color a) Red, green, and blue b) Cones are densely concentrated in the macula
c. Outer nuclear layer: contains cell bodies of photoreceptors
d. Outer plexiform layer: contains synapses between photoreceptors and bipolar and horizontal cells
e. Inner nuclear layer 1) Amacrine cells are horizontally oriented, dopaminer-
gic cells that modulate and convey photoreceptor information to ganglion cells
2) Bipolar cells convey photoreceptor information to ganglion cells
3) Horizontal cells provide antagonistic surround signals to bipolar cells
f. Inner plexiform layer: contains synapses between bipolar and amacrine cells and ganglion cells
g. Ganglion cell layer 1) Most superficial retinal layer 2) Ganglion cells divided into M and P cells 3) M and P cell axons project to superior colliculus or
lateral geniculate nucleus 4) M cells lack color information, but have high contrast
sensitivity, fast temporal resolution, low spatial resolution
5) M cell axons project to magnocellular neurons in layers 1 and 2 of lateral geniculate nucleus, and these neurons project to layer IVC alpha neurons in cortical area 17
6) P cells have color opponency, low contrast sensitivity, and high spatial resolution
7) P cell axons project to parvocellular neurons in layers 3, 4, 5, and 6 of lateral geniculate nucleus, and these neurons project to layer IVC alpha neurons in cortical area 17
8) Two types of signal processing a) ON center, OFF surround
i) ON center: activated when light hits center of the receptive field
ii) OFF surround: deactivated when light hits periphery of the receptive field
b) OFF center, ON surround: center receptive field stimulation is OFF, and peripheral stimulation is ON
c) ON-OFF signal processing helps establish sharp boundaries of objects in visual field
9) Ganglion cell axons traveling to the optic nerve form the retinal nerve fiber layer
C. Retinal Nerve Fiber Layer 1. Papillomacular bundle: nerve fibers extending from
macula to optic nerve 2. Temporal nerve fibers arch around papillomacular bun-
dle to reach optic disc 3. Optic nerve creates a physiologic blind spot on visual
field testing (temporal) 4. Scotomas (“blind spots”): areas of poor or absent
vision within the visual field 5. Specific scotoma and visual field abnormalities may
occur from optic nerve and retinal lesions based on arrangement of retinal nerve fiber layer a. Arcuate scotoma or defects: arch-shaped, characteristic
of nerve fiber bundle defects (e.g., glaucoma) (Fig. 3-4)
b. Central scotoma (macular type of defect): a blind spot in the visual field represented by the macula (e.g., macular degeneration) (Fig. 3-5 left)
c. Centrocecal scotoma (optic nerve type of defect): affects the visual field in region of the macula and papillomacular bundle (Fig. 3-5 right)
d. Paracentral scotoma: affects retina and visual field just outside the macula (Fig. 3-6 left)
e. Ring scotoma: from combined superior and inferior retina and arcuate scotoma (Fig. 3-6 right)
f. Ring scotoma with a horizontal step: typically indicates retinal or nerve fiber layer lesion as opposed to ring
Monocular scotoma and noncongruous visual field abnormalities (especially monocular) occur from optic nerve and retinal lesions based on arrangement of retinal nerve fiber layer
scotoma with a vertical step, which may indicate lesion in occipital lobe near calcarine fissure
g. Enlargement of blind spot (e.g., optic disc swelling) (Fig. 3-7)
h. Altitudinal defects: blind spots with a horizontal step; typically appear as an abrupt, monocular loss of superior or inferior visual field
i. Sector scotoma or defects: typically caused by retinal lesion (e.g., retinal detachment) (Fig. 3-8)
j. Noncongruous visual field defects: dissimilar monocular visual field patterns
D. Optic Nerve 1. Segments
a. Intraocular segment (optic nerve head) b. Intraorbital segment c. Intracanalicular (optic canal) segment d. Intracranial segment
2. Topographic arrangement of nerve fiber layer within optic nerve a. Similar to topology of nerve fiber layer before entry into
optic nerve b. Macular fibers (papillomacular bundle) are located
peripherally (temporal aspect of the optic nerve) in the portion of optic nerve closest to the globe
c. Macular fibers become more centrally located in more distal portion of optic nerve closest to the chiasm
d. Peripheral retinal fibers travel peripherally 3. Monocular vision loss is usually due to disease of reti-
na, optic disc, or optic nerve: anterior to optic chiasm a. Central field defects are caused by lesions that affect optic
nerve, macula, or papillomacular bundle 1) Unilateral central scotomas, for example, optic neu-
ropathy, optic neuritis, or macular degeneration 2) Bilateral central or centrocecal defects, for example,
suggestive of bilateral optic neuropathies (hereditary, compressive, nutritional, inflammatory) or bilateral occipital lesions
b. Unilateral temporal defects 1) Lesion of nasal retina, optic nerve, or nasal optic nerve
fibers at anterior optic chiasm (e.g., junctional scotoma of Traquair, see below)
2) Monocular temporal crescent: retinal disease or lesion of anterior occipital lobe
c. Altitudinal defects: characteristic of disease of the central retinal artery, with macular sparing (cilioretinal arteries) or posterior ciliary artery (anterior ischemic optic neuropathy)
E. Optic Chiasm 1. Nasal retinal nerve fibers: cross to contralateral optic
tract at level of the optic chiasm (constitute about half of optic nerve fibers)
2. Inferior nasal fibers of one optic nerve cross ventrally into contralateral optic nerve proximally and are known as Wilbrand’s knee (Fig. 3-1), (the existence of this anatomic entity has been questioned)
3. Temporal retinal nerve fibers remain ipsilateral in optic chiasm and optic tracts
4. Posterior to optic chiasm: pituitary stalk 5. Optic chiasm lesions: bitemporal field defects, almost
never complete bitemporal field defects and exact field defect depends on localization of the compressive lesion a. Anterior chiasm (Fig 3-1)
1) Compressive lesion anterior to optic chiasm generally causes bitemporal field defects involving the upper quadrants early on (may eventually evolve to more extensive bitemporal field defects)
2) Junctional syndrome of Traquair a) Monocular superior temporal field defect in eye
contralateral to the lesion b) Often due to early, anterior chiasmal compressive
lesion limited to crossing fibers from inferonasal retina of contralateral eye (Wilbrand’s knee), situated anterior to the ipsilateral inferonasal fibers (Fig. 3-1, left lower inset, C)
3) Junctional syndrome a) Ipsilateral central scotoma with contralateral supe-
rior temporal defect b) Due to compression of Wilbrand’s knee and ipsi-
lateral optic nerve (Fig. 3-1, defect 4, Fig. 3-9)
4) Bilateral superior temporal field defects due to early anterior compression of both inferonasal crossing fibers
b. Body of the chiasm syndrome: typically bitemporal visual field defects (often incomplete, may be limited to central fields, peripheral fields, or both)
c. Posterior chiasm syndrome 1) Compressive lesion posterior to optic chiasm general-
ly causes bitemporal field defects involving lower quadrants early on (may eventually evolve to more extensive bitemporal field defects)
2) Bilateral temporal scotomas (involving central vision, peripheral fields spared)
3) Bitemporal field defects primarily affecting inferior temporal fields due to early compressive lesions
F. Optic Tracts 1. Optic chiasmal fibers leading to lateral geniculate
nucleus 2. Visual field defect related to lesion involving optic tract
a. Complete (macular-splitting) homonymous hemianopia b. Wallerian degeneration and dying-back axonal loss caus-
ing ganglion cell fiber atrophy of contralateral nasal macula and nasal retina and ipsilateral temporal retina
c. Contralateral relative afferent pupillary defect: optic tract lesion on one side may cause the contralateral eye to have a relative afferent pupillary defect (i.e., greater number of crossed vs. uncrossed fibers in chiasm, 53:47) and a temporal visual field defect
d. This is the last post-chiasmal site for a relative afferent pupillary defect other than an asymmetric posterior midbrain lesion
G. Lateral Geniculate Nucleus 1. Has six layers (Fig. 3-1, bottom right inset) 2. Superior retinal fibers lie superomedial in the nucleus
Junctional syndrome: an anterior chiasm lesion causes a central scotoma in one eye and a superior temporal visual field defect in the other eye (Fig. 3-9)
Bitemporal visual field defects are typical of a lesion affecting the body of the optic chiasm
Nasal retinal fibers cross in the optic chiasm and temporal retinal fibers remain ipsilateral
Inferior nasal fibers of one optic nerve cross ventrally into the contralateral optic nerve proximally and are known as Wilbrand’s knee
An isolated monocular temporal field defect affecting the contralateral optic nerve or Wilbrand’s knee is called a junctional scotoma of Traquair
3. Inferior retinal fibers lie lateral in the nucleus 4. Anterior choroidal artery occlusion causes a quadruple
sectoranopia: homonymous defect affecting superior and inferior quadrants, with sparing of the horizontal sectors (Fig. 3-10 A)
5. Posterior lateral choroidal artery occlusion causes a horizontal homonymous sector defect: a homonymous defect of horizontal sectors (wedge-or triangle-shaped) (Fig. 3-10 B)
H. Optic Radiations 1. Optic radiations exit the lateral geniculate nucleus in
three bundles, which course around the lateral ventricle through white matter to reach calcarine cortex (cortical area 17)
2. Three optic radiation bundles a. Upper bundle
1) Originates from medial part of lateral geniculate nucleus
2) Represents superior retina
3) Passes deep in parietal white matter and ends in superior lip of the calcarine fissure
b. Central bundle 1) Originates from medial part of lateral geniculate
nucleus 2) Represents macular region 3) Traverses posterior temporal and occipital white mat-
ter and ends on both lips of posterior part of the calcarine fissure
c. Lower bundle 1) Originates from lateral part of lateral geniculate nucleus 2) Represents inferior retina 3) Courses anteriorly from lateral geniculate nucleus and
then turns around temporal horn of lateral ventricle (Meyer’s loop) to end on inferior lip of the calcarine fissure
3. Superior homonymous quadrantic (“pie in the sky”) defects may result from lesion of Meyer’s loop (i.e., optic radiations that pass through temporal lobe to occipital lobe inferior to the calcarine fissure)
4. Inferior homonymous quadrantic (“pie on the floor”) defects result from lesion of optic radiations that pass
Superior retinal nerve fiber information travels in the superior optic radiations to the superior lip of the calcarine fissure
Inferior retinal nerve fiber information travels in the inferior optic radiations to the inferior lip of the calcarine fissure
Complete homonymous hemianopias indicate retrochiasmal disease (e.g., lateral geniculate nucleus, optic radiations, occipital cortex)
Visual field defects become more congruous (i.e., similar pattern in both eyes) from the lateral geniculate body toward the occipital lobe
A superior homonymous quadrantic (“pie in the sky”) defect may result from a lesion of Meyer’s loop in the temporal lobe or inferior occipital cortex
An inferior homonymous quadrantic (“pie on the floor”) defect results from a lesion of the optic radiations traveling through the parietal lobe or superior occipital cortex
through parietal lobe to occipital lobe superior to the calcarine fissure
I. Visual Cortex (Fig. 3-11) 1. Striate cortex, or primary visual cortex, is Brodmann’s
area 17: located along superior and inferior banks of calcarine fissure
2. Central 10 to 15 degrees of vision represent a disproportionate amount of surface area (50%-60%) of occipital cortex
3. Homonymous quadrantic defects can occur from unilateral occipital lobe lesions; the visual field defects typically have a sharp horizontal edge
4. Medial occipital lesions cause congruous homonymous hemianopias, typically with macular sparing and are usually due to infarcts in territory of the posterior cerebral artery (absolute congruence in comparison with lesions of optic tracts or optic radiations, which are not as congruent)
5. Macular sparing is believed to be due to dual arterial supply (both posterior and middle cerebral arteries supplying the occipital pole responsible for macular vision) and also a larger cortical representation of the macular region
6. Striate cortex lesion localization a. Anterior lesion: causes a temporal crescent or half moon
syndrome in contralateral eye (Fig. 3-1, defect 11); the only retrochiasmal lesion that can cause a unilateral visual field defect
b. Intermediate lesion: affects from 10 to 60 degrees in contralateral hemifield
c. Posterior lesion: affects macular vision (central 10 degrees in contralateral visual field)
7. Cortical blindness: complete blindness or keyhole vision that may result from bilateral occipital lobe disease
8. Anton’s syndrome: cortical blindness with denial of neurologic impairment
A. Introduction 1. Purpose of efferent visual system: direct and maintain
the fovea toward target of interest 2. Efferent visual system has both slow and rapid visual
tracking systems, with voluntary and reflex mechanisms 3. Efferent visual system: supranuclear, nuclear, infranu-
clear and internuclear neurons; neuromuscular junc-
tion; ocular motor muscles 4. “Ocular motor” refers to cranial nerves (CNs) III, IV,
and VI as a group 5. “Oculomotor” refers to CN III only
B. Ocular Muscles (Fig. 3-12 and Table 3-1): six muscles for each eye
1. Four rectus muscles (superior, inferior, medial and lateral)
2. Two oblique muscles (inferior and superior)
C. Cranial Nerve III (oculomotor nerve) 1. Neuroanatomy
a. Oculomotor nuclear complex: located in midbrain at level of the superior colliculus; two unpaired and four paired columns of nuclei within the nuclear complex
With lesions affecting the optic nerve or chiasm, patients may have decreased visual acuity, a relative afferent pupillary defect, and visual field defectsophthalmoscopic findings are usually present
With unilateral retrochiasmal lesions, patients typically have retained visual acuity, no relative afferent pupillary defect, a visual field defect, and usually normal ophthalmoscopic findings-an exception is an optic tract lesion
1) Single caudal central nucleus (unpaired): innervates left and right levator palpebrae superioris muscles
2) Single visceral Edinger-Westphal nucleus (unpaired): most dorsal localization, provides parasympathic innervation of pupil (pupillary constrictors and ciliary muscle)
3) Medial nuclei (paired): each innervates superior rectus muscle ipsilaterally and sends decussating fibers (through contralateral medial nucleus) to contralateral superior rectus muscle (ablative lesion in one medial nucleus causes weakness in superior recti bilaterally); paired nuclei with decussating axons
4) Intermediate nuclei (paired): each innervates ipsilateral inferior oblique muscle
5) Dorsal nuclei (paired): each innervates ipsilateral inferior rectus muscle
6) Ventral nuclei (paired): each innervates ipsilateral medial rectus muscle
b. Fascicular arrangement is maintained similar to nuclear
topology c. Oculomotor fascicles travel ventrally, exit the interpe-
duncular fossa as the oculomotor nerve in the subarachnoid space
d. Subarachnoid space: oculomotor nerve passes between posterior cerebral and superior cerebellar arteries; near the uncus of temporal lobe (and in proximity to posterior communicating artery), it penetrates the dura mater into cavernous sinus (Fig. 3-13)
e. Cavernous sinus: oculomotor nerve is superior and lateral in cavernous sinus and exits the sinus to enter superior orbital fissure (Fig. 3-14)
f. Superior orbital fissure: after entering this fissure, oculomotor nerve divides into superior (innervates superior rectus and levator palpebrae superioris) and inferior (innervates medial and inferior recti and inferior oblique) divisions and provides parasympathetic input to ciliary ganglion
Ocular muscle innervation mnemonic: “SO4 LR6” SO = superior oblique innervated by cranial nerve IV
LR = lateral rectus, innervated by cranial nerve VI
Other ocular muscles are innervated by cranial nerve III
Superior muscles intort or “SIN” mnemonic: the superior oblique (SO) and superior rectus (SR) muscles are intorters of the eye
Table 3-1. Summary of the Extraocular Muscles, Innervation, and Action
Primary Innervation Muscle action Secondary (cranial nerve)
g. Orbit: oculomotor nerve divisions (superior and inferior)
2. Localization of third nerve palsy a. Nuclear lesions: ipsilateral complete pupil-involved third
nerve palsy (including ptosis), contralateral eyelid ptosis, and superior rectus palsy 1) Subnuclear lesions: rare, but can cause isolated mus-
cle paresis (e.g, inferior oblique) or bilateral eyelid ptosis
2) Nuclear lesions may spare Edinger-Westphal nucleus (pupil-sparing lesion)
3) Differential diagnosis: focal hemorrhage, infarct, or mass (neoplastic, vascular malformation)
b. Fascicular lesions 1) Plus-minus syndrome (within midbrain): example of
fascicular lesion causing ipsilateral ptosis and contralateral eyelid retraction (occurs with midbrain lesions involving fascicles supplying ipsilateral levator palpebrae and inhibitory projections to opposite subnucleus for contralateral levator palpebrae)
2) Differential diagnosis: infarction, hemorrhage, mass, demyelination, infection
3) Ipsilateral syndromes a) Weber’s syndrome: ipsilateral third nerve palsy
with contralateral hemiparesis due to involvement of CN III and cerebral peduncle
b) Nothnagel’s syndrome: ipsilateral third nerve palsy with ipsilateral ataxia (superior cerebellar lesion)
c) Claude’s syndrome: ipsilateral third nerve palsy and contralateral ataxia, due to involvement of the tegmentum, red nucleus, and CN III
d) Benedikt’s syndrome: clinical features of Claude’s syndrome plus contralateral hemiparesis, latter due to involvement of cerebral peduncle
c. Subarachnoid space lesions 1) Posterior communicating artery aneurysm: usually
involves pupils 2) Uncal herniation 3) Tumors and other mass lesions, arachnoid cysts 4) Meningeal (inflammatory or infectious) disease (e.g.,
sarcoidosis, tuberculosis) 5) Small-vessel ischemia in setting of diabetes mellitus
(often pupil sparing, painful) or vasculitis d. Cavernous sinus lesions (Fig. 3-14)
1) Third nerve palsy with or without pain 2) Third nerve palsy with some combination of other
cavernous sinus constituents: CNs IV, VI, ophthalmic division of V (V1) (and sometimes maxillary division of V [V2] anatomy variable)
3) Third nerve palsy and Horner’s syndrome (sympathetic fibers along carotid artery)
4) Masses of cavernous sinus may cause aberrant regeneration of CN III
5) Differential diagnosis a) Compressive lesions: pituitary adenoma and other
neoplastic compressive lesions, carotid-cavernous fistulas, pituitary apoplexy, aneurysm of intracavernous portion of internal carotid artery, cavernous sinus thrombosis
b) Cavernous sinus infection with Mucor or Aspergillus, usually in setting of diabetes or immunosuppression
c) Inflammatory (e.g., Tolosa-Hunt syndrome) e. Superior orbital fissure lesions
1) Third nerve palsy with possible palsies of CN IV, VI, V1
2) Differential diagnosis (similar to the cavernous sinus lesions): inflammatory (Tolosa-Hunt syndrome,
granulomatous disease often affecting superior orbital fissure), compressive lesions such as tumors (e.g., meningioma, metastatic tumor)
f. Orbital lesions 1) Divisional third nerve palsy, optic neuropathy, prop-
tosis, orbital injection, chemosis 2) Differential diagnosis
a) Compressive lesions (neoplastic, including meningioma and metastatic tumors, and vascular malformations)
b) Trauma (orbital fractures) c) Inflammatory (idiopathic orbital pseudotumor)
g. Disorders of neuromuscular transmission 1) Myasthenia gravis 2) Lambert-Eaton myasthenic syndrome
h. Disorders of muscle 1) Graves’ ophthalmopathy (most often affecting inferi-
or rectus muscle) 2) Dystrophic myopathies (e.g., oculopharyngeal
dystrophy) 3) Ocular neuromyotonia: rare, episodic diplopia in set-
ting of previous radiotherapy, usually in sellar or parasellar regions
i. Other nonlocalizing causes 1) Miller Fisher variant of Guillain-Barré syndrome 2) Ophthalmoplegic migraine: most frequently involv-
ing the oculomotor nerve and, commonly, the pupillary response and accommodation
3) Lyme disease with meningeal involvement 3. Pupillary involvement (“the rule of the pupil”)
a. Pupillomotor fibers are located superficially (peripherally) in CN III and tend to be spared by ischemic insults (which primarily affect deep fibers)
b. Pupil-sparing third nerve palsy occurs with nerve infarction in setting of diabetes, giant cell arteritis, or systemic lupus erythematosus
c. Compressive lesions generally tend to affect pupils (may be delayed)
d. Exceptions to “the rule of the pupil”: partial third nerve palsy or partial pupillary involvement 1) Some ischemic lesions due to diabetes may produce
minimal anisocoria 2) Aneurysms presenting with partial oculomotor palsies
may have minimal involvement of pupillomotor fibers (relative pupillary sparing)
3) Certain cavernous sinus or subarachnoid partial compressive lesions involving only portions of CN III carrying no pupillary fibers
4) The pupillary function is also spared by a) Some slow-growing tumors sparing pupillary fibers
that tend to be more pressure-resistant than underlying oculomotor fibers
b) Acute stage of a rapidly expanding mass (becomes more obvious later)
D. Cranial Nerve IV (trochlear nerve) 1. Neuroanatomy (Fig. 3-15)
a. Nucleus: trochlear nucleus is at level of inferior colliculus
b. Fascicles: travel posteriorly around cerebral aqueduct, decussate, and exit brainstem under the inferior colliculi
c. Subarachnoid space 1) CN IV: only cranial nerve to exit dorsally 2) CN IV and CN III innervation of contralateral supe-
rior rectus muscle: only cranial nerves with axons that decussate
3) CN IV travels through quadrageminal, ambient, crural, and pontomesencephalic cisterns
4) CN IV travels in proximity to tentorium cerebellum: entrapment may occur at edge of the tentorium
d. Cavernous sinus: CN IV enters cavernous sinus inferior to CN III, the lateral aspect of the clivus, and lies within lateral wall of cavernous sinus (Fig. 3-14)
e. Superior orbital fissure: CN IV exits cavernous sinus and enters superior orbital fissure
f. Orbit: within the orbit, CN IV innervates superior oblique muscle
2. Localization of fourth nerve palsy (differential diagnosis similar to third nerve palsy) a. Nuclear and fascicular lesions
1) Contralateral fourth nerve palsy
2) Anterior medullary velum lesions: bilateral fourth nerve palsies (common cause in children is medulloblastoma)
b. Subarachnoid space (CN IV): ipsilateral fourth nerve palsy
c. Cavernous sinus: ipsilateral fourth nerve palsy with combination of deficits involving cavernous sinus constituents (CN III, VI, V1, sympathetic innervation of orbit [Horner’s syndrome])
d. Superior orbital fissure and orbit: ipsilateral fourth nerve palsy with possible combination of CN III, VI, or V1
E. Cranial Nerve VI (abducens nerve) 1. Neuroanatomy (Fig. 3-16)
a. Nucleus: abducens nucleus is in pons and adjacent to floor of fourth ventricle
b. Fascicles: abducens fascicles travel ventrally through pons and emerge at pontomedullary junction
c. Subarachnoid space 1) Long intracranial upward course: CN VI travels
through prepontine cistern subarachnoid space, enters Dorello’s canal beneath petrosphenoidal ligament of Gruber to enter cavernous sinus
2) Lesion can cause “false localizing sign” (see below)
d. Cavernous sinus: CN VI lies inside cavernous sinus (Fig. 3-14)
e. Superior orbital fissure and orbit: CN VI exits cavernous sinus, passes through superior orbital fissure into orbit to innervate lateral rectus muscle
2. Localization of sixth nerve palsy (differential diagnosis similar to third nerve palsy) a. Pons (nucleus and fascicles)
1) Ipsilateral sixth nerve palsy for discrete lesion 2) Foville’s syndrome (see also Chapter 4)
a) Ipsilateral lower motor neuron facial paralysis b) Ipsilateral gaze paralysis (abducens nucleus lesion) c) Contralateral hemiparesis
3) Millard-Gubler syndrome (see also Chapter 4) a) Ipsilateral lower motor neuron facial paralysis b) Ipsilateral abducens paralysis c) Contralateral hemiparesis
b. Subarachnoid space 1) Ipsilateral sixth nerve palsy 2) Gradenigo’s syndrome (lesion of petrous apex or
Dorello’s canal) a) Ipsilateral sixth nerve palsy: CN VI may be
stretched over the petrous ridge b) Ipsilateral facial pain
c) Ipsilateral deafnesss (CN VIII) d) Due to compressive neoplastic or vascular malfor-
mation, inferior sinus thrombosis 3) False localizing sign in setting of increased intracranial
pressure (e.g., hydrocephalus, pseudotumor cerebri)—CN VI has longest intracranial course of all cranial nerves and is more predisposed to stretch-induced injury, especially with shearing over the petrous ridge
c. Cavernous sinus: ipsilateral sixth nerve palsy for discrete lesion with possible involvement of CN III, IV, V1 or Horner’s syndrome
d. Superior orbital fissure and orbit: similar to cavernous sinus but may have orbital signs (e.g., proptosis, injection, chemosis)
F. Smooth Pursuit (Fig. 3-17) 1. Keeps an image on the fovea during slow movement of
an object, such as a line moving slowly across an optokinetic drum
2. Cannot be created voluntarily 3. Must be slower than 5 degrees per second to maintain
vision with high resolution and high visual acuity 4. Visual targets moving faster than 50 degrees per second
induce voluntary fast saccades 5. Stimuli for smooth pursuits may be visual or nonvisual
a. Example of a nonvisual stimulus: proprioceptive input guiding the subject to make pursuit eye movements that follow movements of the limbs in the dark (or with eyes closed)
6. Temporary volitional anticipatory (predictive) pursuit movements also occur in response to predictable target motion, based on previously learned experience a. Examples: predictive movements of the eyes in anticipa-
tion of onset of movement of the visual target (even in the absence of movement of the target) or predictive acceleration of the eye movements when the visual target actually moves
b. These depend on memory for previous tracking experiences
7. Afferent visual information is conveyed to striate cortex and then to occipitotemporal region called medial temporal (MT) and medial superior temporal (MST) areas
8. From MT/MST, information on speed and direction of moving target is conveyed ipsilaterally via arcuate fiber bundles to posterior parietal cortex and contralaterally through corpus callosum to contralateral MT/MST
9. Posterior parietal cortex: directs attention to moving visual stimuli
10. Frontal eye fields and supplementary eye fields a. Have reciprocal connections with posterior parietal
cortex and MT/MST b. Both fields are responsible for predictive pursuit
movements 11. Pursuit pathways: descend to dorsolateral and lateral
pontine nuclei via internal capsule and cerebral peduncles
12. Nucleus of the optic tract a. Pretectal localization in brachium of the superior
colliculus b. Receives retinal input from superior colliculus and corti-
cal input from MT/MST and striate cortex c. Projects to pontine nuclei and superior colliculus:
important for initiating pursuit movements 13. Cerebellar flocculus and paraflocculus: important role
in executing smooth pursuit eye movements and in gaze-holding
14. Impairment
Bilateral dysfunction of smooth pursuit system has many nonspecific causes (fatigue, medications, old age, dementia, bilateral smooth pursuit pathway lesions)
Smooth pursuit deficit toward one side usually indicates unilateral lesion(s)
a. With impairment of pursuit eye movements, compensatory catch-up saccades are produced, causing saccadic pursuit eye movements
b. Symmetric saccadic pursuit movements are nonspecific and may occur in several degenerative and toxic or metabolic conditions
c. Asymmetric or unilateral abnormalities of pursuit eye movements may indicate unilateral lesion somewhere in the pathway
d. Unilateral cerebral hemisphere lesions 1) May cause abnormal pursuit and/or impaired tracking
of objects to the side of the lesion 2) Often may cause contralateral visual neglect after an
acute lesion
G. Saccades 1. Fast (300-700 degrees per second) eye movements that
bring visual images of interest onto the fovea 2. Types of saccades
a. Intentional saccades: bring an item quickly into vision b. Antisaccades: intentional saccades made to look away
from an object; requires suppression of saccade toward a novel stimulus and generation of a saccade away from the stimulus (frontal eye fields and prefrontal cortex are probably largely responsible)
c. Reflexive saccades: in response to sudden movement or sound
d. Spontaneous saccades: occur spontaneously at rest or with speech
3. Two mathematical elements of saccades a. Pulse (velocity) command b. Step (position) command
4. Pulse-slide-step: gradual transition from the end of the velocity command to a position command
5. Three cortical areas involved with creating saccades (Fig. 3-18) a. Frontal eye field (Brodmann areas 4 and 6)
1) Intentional saccades help explore visual environment 2) Projects to superior colliculus: responsible for volun-
tary, intentional change in gaze in response to anticipated or learned experience
3) Lesion causes ipsilateral horizontal gaze deviation (“looks to the lesion”), whereas stimulation (e.g., focal seizure) causes eyes to deviate toward contralateral side
b. Parietal eye field 1) Visual attention and visually guided saccadic control 2) Projects to frontal eye field: contributing to initiation
of saccades 3) Projects to superior colliculus: responsible for adjust-
ing gaze and reflexive visual attention to a new visual
stimulus to explore the environment c. Supplementary (frontal) eye fields
1) Located in posterior and medial aspect of superior frontal gyrus (supplementary motor cortex)
2) Responsible for motor programs (made of several saccades, complex saccades) as part of learned behavior
6. Other areas involved with saccades a. Dorsolateral prefrontal cortex
1) Responsible for planning of saccades to target locations; controls inhibition of reflexive visually guided saccades
2) Degenerative disease of prefrontal lobe: patients have difficulty performing antisaccades or suppressing unwanted reflexive saccades (as may occur during visual field examination, “visual grasp reflex”)
b. Posterior parietal cortex 1) Directing visual attention 2) Visual-spatial integration 3) Calculating saccadic amplitude 4) Projects predominantly to prefrontal cortex, only
minor projections to frontal eye field c. Medial temporal lobe: controls chronologic order of
sequences of saccades d. Pulvinar
1) Input from retina, superior colliculus, cortex 2) Projects to parietal cortex and guides shifting visual
attention 3) Responds to movement of image on retina
1) Calculates eye velocity and stationary commands based on eye position and retinal information
2) Responsible for the “step” (i.e., the tonic discharge responsible for maintenance of eye position) after new position is obtained
4) Roles: maintains accuracy of saccades and directs visual attention to novel stimuli
e. Superior colliculus 1) Responsible for reflexive visually guided saccades 2) Receives input from parietal and frontal lobes 3) Projects to burst cells in brainstem 4) Frontal eye field and supplementary frontal eye field
project directly to brainstem burst cells in parallel with superior colliculus projection
f. Basal ganglia: responsible for memory-guided and anticipatory saccades (relay for indirect projections of frontal eye field, supplementary eye field, and prefrontal cortex to superior colliculus)
g. Cerebellum 1) Fastigial nucleus projects to brainstem (especially
omnipause cells and burst cells) via uncinate fasciculus
2) Destructive fastigial lesions: tend to be bilateral and produce severely hypermetric saccades in all directions
3) Unilateral ablation of fastigial nucleus: hypermetria of ipsilateral saccades and hypometria of contralateral saccades
4) Severe dysmetria (hypermetria) of saccades may give the appearance of macrosaccadic oscillations (may also be seen in patients with visual field defects who make excessive hypermetric saccades to explore defective visual field)
5) Flocculus lesions: gaze-evoked nystagmus without saccadic pulse dysmetria (primary function affected is gaze holding)
7. Summary of anatomic projections responsible for saccades a. Parietal eye fields, prefrontal cortex, frontal eye field, sup-
plementary eye field all project to superior colliculus b. Both supplementary eye field and frontal eye field pro-
ject directly to superior colliculus and brainstem saccade centers
c. Superior colliculus projects to brainstem saccade centers d. Frontal eye field and supplementary eye field also project
indirectly to superior colliculus via basal ganglia 8. Brainstem regulation of saccades (Fig. 3-19)
a. Excitatory burst neurons: responsible for the “pulse,” the quick change in eye position
b. Omnipause neurons 1) Are located in midpons 2) Send tonic inhibitory projections to burst cells
c. Signals from frontal lobe and superior colliculus act to inhibit omnipause cells and initiate a saccade by allowing burst cells to fire
d. Neural integrator
e. Inhibitory burst neurons: inhibit saccades 9. Horizontal saccades
a. Excitatory burst neurons 1) Located in PPRF (Fig. 3-19) 2) Project to ipsilateral abducens nucleus, which then
projects to contralateral oculomotor nucleus via MLF 3) Horizontal saccades are generated toward the side of
the PPRF that initiates them b. Horizontal gaze neural integrators: nucleus prepositus
hypoglossi and medial vestibular nucleus c. Inhibitory burst neurons for horizontal saccades
1) Are caudal to abducens nucleus 2) Inhibit contralateral abducens nucleus from initiating
contralateral horizontal saccades 10. Horizontal conjugate gaze palsy
a. Ablative lesions involving frontal eye field cause patient to “look at the lesion” in the acute phase
b. Excitatory focus of frontal eye field causes patient to “look away from the lesion”
c. Lesions involving the prefrontal cortex produce difficulty performing antisaccades or suppressing unwanted reflexive saccades
d. Ablative pontine lesions involving excitatory burst neurons (PPRF) and horizontal gaze neural integrator causes patient to “look away from the lesion”
e. Excitatory focus involving PPRF causes patient to “look toward the lesion”
11. Horizontal dysconjugate gaze palsy a. Internuclear ophthalmoplegia (INO) (Fig. 3-20)
1) MLF lesion: weakness of ipsilateral medial rectus, especially evident when making horizontal saccades opposite the side of the paretic muscle
2) This adductor paresis is often associated with jerk nystagmus in the abducting eye
3) Slowing of the adducting saccade may be the only sign of partial INO
4) Bilateral INOs (often asymmetric, partial) frequently seen with multiple sclerosis, but pontine infarct often causes unilateral complete INO
b. One-and-a-half syndrome: combined unilateral conjugate gaze palsy and INO (Fig. 3-21) 1) Horizontal gaze paresis in one direction plus medial
rectus weakness, usually due to pontine lesions affecting abducens nucleus or PPRF and MLF ipsilateral to complete gaze paresis
2) Often due to focal lesions of pons (e.g., multiple sclerosis, hemorrhage, infarct)
c. Wall-eyed bilateral INO (WEBINO): marked bilateral exotropia caused by critical lesion of bilateral MLFs
12. Vertical saccades
a. Excitatory and inhibitory burst neurons for vertical and torsional saccades are in the midbrain in rostral interstitial nucleus of MLF
b. Vertical neural integrator: interstitial nucleus of Cajal c. Axons from vestibular nuclei cross in MLF to contralat-
eral interstitial nucleus of Cajal, rostral interstitial nucleus of MLF and trochlear and oculomotor nuclei to generate vertical gaze
d. Interstitial nucleus of Cajal (vertical neural integrator) projects through posterior commissure to contralateral interstitial nucleus of Cajal and oculomotor and trochlear nuclei
13. Vertical conjugate gaze palsy a. Rostral brainstem lesions involving both interstitial
nucleus of Cajal and rostral interstitial nucleus of MLF can produce vertical gaze palsies 1) Thromboembolism at bifurcation of basilar artery can
affect Percheron’s artery (thalamic-subthalamic paramedian artery), with infarction involving medial thalami and rostral midbrain, including the rostral interstitial nucleus of MLF, bilaterally
2) Bilateral thalamic involvement may cause coma
3) Bilateral rostral midbrain lesion may cause vertical gaze palsy (which may not be obvious in comatose patient)
b. Dorsal midbrain lesions affecting posterior commissure can cause vertical upward gaze palsy, often with downward ocular deviation 1) Vestibulocephalic vertical eye movements (doll’s eyes)
may be intact if other vertical gaze centers are intact 2) However, when lesions affect nuclear vertical gaze cen-
ters, vertical gaze paresis cannot be overcome by cold water caloric testing or doll’s eyes maneuvers
3) Associated symptoms: light-near dissociation (poorto-absent pupil reactivity to light with preservation of near reaction), absent or excessive convergence, convergence-retraction nystagmus, and Collier’s sign (bilateral upper eyelid retraction)
4) This constellation of symptoms: dorsal midbrain syndrome (Parinaud’s syndrome)
c. Right hemispheric strokes have been associated with bilateral ptosis (or apraxia of eyelid opening) and up-gaze palsies
d. Huntington’s disease: increased saccadic latencies e. Progressive supranuclear palsy
1) Vertical (especially downward) more than horizontal saccades affected earlier than pursuit movements
2) Slow and hypometric saccades: due to degenerative involvement of rostral interstitial nucleus of MLF (voluntary saccades to command often affected first and earlier than smooth pursuits)
3) Absence of Bell’s phenomenon 4) Limitation of convergence and “wide-eyed stare” due
to bilateral exophoria and bilateral lid retraction 5) Apraxia of eyelid movements (especially opening) 6) Saccadic intrusions on primary gaze and square wave
jerks due to degenerative involvement of superior colliculus
7) Reduced vestibulo-ocular reflex (VOR) suppression 8) Reduced fast component of optokinetic nystagmus 9) Smooth pursuit movements may also be abnormal
because of pontine involvement 10) Frontal lobe involvement may produce abnormal
antisaccades 11) Eventually, complete bilateral ophthalmoplegia
f. Parkinson’s disease: associated with abnormal smooth pursuit movements and hypometric saccades, especially late in disease course
g. Oculogyric crisis 1) Characterized by upward ocular deviation and mental
status changes, sometimes accompanied by dystonic deviation of tongue and choreoathetosis
2) Most commonly due to medications such as neuroleptics
3) May also be seen (rarely) in Wilson’s disease, acute bilateral thalamic lesions, paraneoplastic syndrome, rhombencephalitis, and several degenerative conditions
h. Setting sun sign: downward ocular deviation in preterm infants with intraventricular hemorrhage
i. Sustained upward ocular deviation in severe hypoxic encephalopathy
j. Paroxysmal upward ocular deviation may occur as epileptic phenomenon and also oculogyric crisis (discussed above)
14. Vertical dysconjugate gaze palsy a. Skew deviation: vertical ocular misalignment due to
supranuclear lesions, lesions involving projections from utricle to interstitial nucleus of Cajal, cerebellum, or different areas of brainstem 1) Ocular tilt reaction: skew deviation associated with
conjugate ocular torsion or head tilt a) Head tilt and ocular torsion are usually toward side
of hypotropic skewed eye b) This ipsiversive ocular tilt reaction results from
lesion of ipsilateral otoliths, ipsilateral vestibular nerve, or ipsilateral vestibular nucleus disrupting otolithic input to interstitial nucleus of Cajal
c) Lesions of interstitial nucleus of Cajal or rostral interstitial nucleus of MLF cause contraversive ocular tilt reaction
2) Pretectal lesions may cause slowly alternating skew deviation, in which there is a cyclical swap of the ocular positions, such that the hypertropic eye falls as the hypotropic eye rises (may also occur with acute hydrocephalus, tentorial herniation, or Wernicke’s encephalopathy)
b. Vertical dysconjugate ocular misalignment: may be due to myasthenia gravis, Graves’ thyrotoxicosis (most often affecting inferior rectus muscle), or isolated fourth nerve palsy or partial third nerve palsy
H. Vestibulo-ocular Reflex (VOR) 1. Moves eyes in direction opposite to rotation of the head
(conjugate, equal eye movements) and acts to keep image stable on the retina
2. Three semicircular canals (on each side) send signals to vestibular nuclei
3. Bending of hair cells in vestibular labyrinth toward the kinocilium depolarizes axons in vestibular nerve
4. Turning head to the left causes endolymph to flow in opposite direction, activating hair cells in left horizontal canal (Fig. 3-22)
5. This activates ipsilateral lateral vestibular nucleus (which projects to ipsilateral oculomotor nucleus via ascending tract of Deiters) and medial vestibular nucleus (which projects to contralateral abducens nucleus, and this nucleus then projects to contralateral oculomotor nucleus, i.e., ipsilateral to the stimulated vestibular nuclei)
6. Result: excitation of ipsilateral CN III and contralateral CN VI and eye deviation to the right with left head turn
7. Downward head deviation activates left and right anterior semicircular canals and generates upward deviation of the eyes
8. Upward head deviation activates left and right posterior semicircular canals and generates downward deviation of the eyes when the gaze is fixed on an object
9. With pure vertical movements, torsional components are activated equally in opposite directions and block each other
10. Downward head deviation with torsional rotation activates ipsilateral anterior semicircular canal, ipsilateral
superior rectus muscle, and contralateral inferior oblique muscle
11. Upward head deviation with torsional rotation activates ipsilateral posterior semicircular canal, ipsilateral superior oblique muscle, and contralateral inferior rectus muscle, producing depression and torsional movement of both eyes toward opposite side
12. VOR gain: ratio of eye velocity to head velocity (opposite directions); this ratio must equal 1 to keep vision stable
13. Ways to examine VOR gain a. Dynamic illegible E (or visual acuity) test (with rapid
head shaking) 1) Instruct patient to read a Snellen chart test while
shaking the head at a steady rate between 2 and 3 Hz 2) A decrease in visual acuity more than 2 lines indicates
abnormal VOR gain (underactive or overactive) b. Ophthalmoscopic examination (with rapid head shak-
ing): examiner concentrates on and follows the optic disc while shaking patient’s head at 2 to 3 Hz
I. Convergence Spasm 1. Crossing eyes periodically with otherwise normal
neuro-ophthalmologic examination (e.g., full ductions) 2. Characteristic finding: presence of miosis during the
spasm 3. Most often occurs in the setting of psychogenic disease 4. The differential diagnosis: divergence weakness or
esotropia/excess convergence due to posterior fossa lesions or acute thalamic hemorrhage
J. Other Causes of Ocular Motor Dysfunction 1. Botulism: extraocular muscle paresis like myasthenia
gravis but also affects pupil reactivity and accommodation
2. Fisher syndrome (Miller Fisher syndrome) a. Rare variant of acute inflammatory demyelinating
polyradiculopathy b. Clinical features: ataxia, ophthalmoplegia, and areflexia
3. Bell’s phenomenon a. Physiologic upward (and oblique) rotation of globe with
eye closure
Lesions afffecting the pons generally cause horizontal gaze abnormalities
Lesions affecting the midbrain generally cause vertical gaze abnormalities
b. Patients with psychogenic spells may have partial eye closure and opening showing the white of the eye as if rolling in the back of the head in the process of normal eye closure and may demonstrate Bell’s phenomenon while forcefully attempting to close eyes against examiner’s manual attempt to open eyelids
A. Loss of Vision 1. History
a. Loss of vision: monocular or binocular? b. Temporal profile of the loss of vision: transient or
persistent? progressive or nonprogressive? acute or gradual onset?
