(From Lawton AW: Retrochiasmal pathways, higher cortical function, and nonorganic visual loss. In: Yanoff M, Duker JS (eds) Ophthalmology, 2nd edn. St Louis, Mosby, 2004.)

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Figure 4-7 Pathways for vertical gaze. Upgaze pathways originate in the rostral interstitial nucleus of the medial longitudinal fasciculus and project dorsally to innervate the oculomotor and trochlear nerves, traveling through the posterior commissure. Lesions to both axon bundles are necessary to produce upgaze paralysis (lesions B or C). Upgaze paralysis is a feature of the dorsal midbrain syndrome as a result of the lesion’s effect on the posterior commissure (lesion A). Downgaze pathways also originate in the rostral interstitial nucleus of the medial longitudinal fasciculus but probably travel more ventrally. Bilateral lesions also are needed to affect downgaze and usually are located dorsomedial to the red nucleus.

(From Donahue SP, Lavin PJM: Disorders of supranuclear control of ocular motility. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Physiology

Testing

Color vision tests

Ishihara pseudoisochromatic or Hardy-Rand-Ritter plates; Farnsworth tests

Congenital defects: usually red / green

Acquired macular disease: may diminish blue / yellow in early stages (blue cones concentrated in perifoveal ring)

Fovea has mostly red / green cones, so red / green defects are detected in optic nerve diseases. Perception of red object indicates gross macular function

Photostress recovery test

determine best-corrected vision, shine bright light into eye for 10 seconds, record time for vision to recover within 1 line of best-corrected vision; test each eye separately; invalid for eyes with vision worse than 20/80

Optic nerve disease: normal recovery time (<60 seconds)

Macular disease: prolonged time (>90 seconds)

Contrast sensitivity

Pelli-Robson chart; Regan contrast sensitivity chart; VectorVision chart

Visually evoked cortical potentials / responses (VEP, VER)

measure macular visual function, integrity of primary and secondary visual cortex, and continuity of optic nerve and tract radiations; fovea has large area in occipital cortex, close to recording electrodes; smaller area representing more peripheral retina lies deep within calcarine fissure (Figure 4-8)

Can measure vision in preverbal infants

Flash VER: strobe light

Pattern VER: checkerboard pattern or bar grating (amacrine and ganglion cell layer of retina)

P100 wave: positive deflection at 100 ms; amplitude is height from peak to trough, latency is time from onset of flash to peak of wave

Toxic or compressive optic neuropathies: reduction of amplitude more pronounced than prolongation of latency

Demyelination: latency is prolonged; amplitude may be only mildly reduced

Figure 4-8 Normal visual evoked cortical response.

(Reprinted with permission from Slamovits TL: Basic and clinical science course. Section 12: Retina and Vitreous. San Francisco, American Academy of Ophthalmology, 1993.)

Amsler grid

tests central 10° of the visual field (held at 35 cm); 10 cm × 10 cm grid composed of 5-mm squares; primarily used to evaluate foveal pathology

Optokinetic nystagmus (OKN)

presence suggests visual input is present; slow phase is noted in direction of moving stimulus

Parieto-occipital area controls slow pursuit, frontal lobe controls saccades

Pathway in visual association area terminates in ipsilateral pontine gaze center, resulting in pursuit movements to the same side (i.e. right visual association area controls pursuit to the right)

Can use to diagnose functional visual loss

Normal (symmetric) OKN response: occipital lobe, temporal lobe, LGB, or optic tract lesions do not interfere with pursuit

Deficient pursuit movements to side of lesion (asymmetric OKN): parietal lobe lesion

Cogan’s dictum (for homonomous hemianopia): asymmetric OKN indicates parietal lobe lesion; symmetric OKN indicates occipital lobe lesion

Reversal of OKN response: 60% of patients with congenital motor nystagmus

Dorsal midbrain syndrome: downward moving OKN drum causes convergence–retraction nystagmus

Congenital ocular motor apraxia: loss of voluntary horizontal gaze (vertical gaze intact); abnormal OKN (fast phase absent); maintained tonic deviation; requires neuroimaging

Potential acuity meter (PAM)

projects image of letter chart onto retina to test macular potential in patients with media opacities

Purkinje vascular phenomena and blue field entopic test

visualization of retinal vasculature; indicates gross retinal function

Visual Field (VF) Defects (Figure 4-9)

Types

Blind spot: physiologic due to ON; 15° temporal to fixation and slightly below horizontal midline

Baring of blind spot: glaucoma, normal patients

Cecocentral scotoma: involves blind spot and macula (within 25° of fixation); can occur in any condition that produces a central scotoma, dominant optic atrophy, Leber’s optic atrophy, toxic / nutritional optic neuropathy, optic pit with serous retinal detachment, optic neuritis

Central scotoma: unilateral (optic neuritis, compressive lesion of ON, retinal lesion [macular edema, disciform scar]); bilateral (toxic optic neuropathy, nutritional deficiency, macular lesions)

Arcuate scotoma: glaucoma, optic neuritis, anterior ischemic optic neuropathy (AION), branch retinal artery occlusion (BRAO), branch vein occlusion (BVO), ON drusen

Altitudinal defect: damage to upper or lower pole of optic disc; optic neuritis, AION, hemiretinal artery or vein occlusion

Spiraling of VF: suggests malingering / functional visual loss

Pseudobitemporal hemianopia (slope and cross-vertical meridian): uncorrected refractive error, tilted optic disc, enlarged blind spot (papilledema), large central or cecocentral scotoma, sector retinitis pigmentosa (nasal quadrant), overhanging lid, coloboma

Binasal defect: most nasal defects due to arcuate scotomas (glaucoma); also, pressure on temporal aspect of ON and anterior angle of chiasm, aneurysm, pituitary adenoma, infarct

Constricted field (ring scotoma): retinitis pigmentosa, advanced glaucoma, thyroid-related ophthalmopathy, ON drusen, vitamin A deficiency, occipital stroke, panretinal photocoagulation, functional visual loss

Neurologic defect: bilateral and respects vertical midline

Figure 4-9 VF defects.

Localizing VF defects

Nerve fiber layer: arcuate, papillomacular, temporal wedge

Chiasm: bitemporal hemianopia (junctional scotoma if involving Willebrand’s knee)

Optic tract: incongruous homonymous hemianopia

Temporal lobe (Meyer’s loop): ‘pie-in-the-sky’ (denser superiorly, spares central)

Parietal lobe: denser inferiorly

Occipital lobe: congruous; ±macular sparing

Neurologic VF defects

Congruity of VF defect (retrochiasmal lesions): the more congruous the defect, the more posterior is the lesion

Superior field: anterior retinal ganglion cells → lateral portion of optic tract → temporal lobe (Meyer’s loop) → inferior bank of calcarine fissure

Vision not reduced by unilateral lesion posterior to the chiasm (20/20 acuity with macula-splitting hemianopia)

Chiasm: pituitary tumor, pituitary apoplexy, craniopharyngioma, meningioma, ON glioma, aneurysm, trauma, infection, metastatic tumor, MS, sarcoid

ANTERIOR CHIASMAL SYNDROME: lesion at junction of ON and chiasm; involves fibers in Willebrand’s knee (contralateral nasal retinal loop); causes junctional scotoma (central scotoma in 1 eye and superotemporal defect in the other)

BODY OF CHIASM: bitemporal hemianopia; vision may be preserved

POSTERIOR CHIASM: bitemporal hemianopia; primarily involves crossing macular fibers

LATERAL COMPRESSION (very rare): binasal hemianopia (more commonly caused by bilateral ON or retinal lesions)

Optic tract: posterior sellar or suprasellar lesions; homonymous hemianopia, contralateral RAPD

Retro-LGB lesions: 90% of isolated homonymous hemianopias due to stroke

Optic radiations:

TEMPORAL LOBE (Meyer’s loop): ‘pie-in-the-sky’ (superior homonymous hemianopia), formed visual hallucinations, seizures

PARIETAL LOBE: inferior homonymous hemianopia, hemiparesis, visual perception difficulty, agnosia, apraxia, OKN asymmetry

GERSTMANN’S SYNDROME: lesion of dominant parietal lobe; acalculia, agraphia, finger agnosia, left–right confusion, associated with inferior homonymous hemianopia if optic radiation involved

Occipital lobe:

HOMONYMOUS HEMIANOPIA WITH MACULAR SPARING: suggests infarct in area supplied by posterior cerebral artery; macular region receives dual supply from both middle cerebral artery and posterior cerebral artery

BILATERAL CONGRUOUS CENTRAL ISLANDS WITH VERTICAL STEP: equivalent to homonymous hemianopia with macular sparing; vertical step does not occur in retinal or optic nerve lesions

CHECKERBOARD FIELD: bilateral incomplete homonymous hemianopias, superior on 1 side and inferior on opposite side (left upper and right lower homonymous quadrant defects)

BILATERAL HOMONYMOUS ALTITUDINAL DEFECTS: infarction or trauma to both occipital lobes, above or below calcarine fissure

MONOCULAR TEMPORAL CRESCENT DEFECT: anterior occipital infarct; far temporal field is seen by only 1 eye

Cortical blindness: bilateral occipital lobe destruction; pupillary response intact, blindsight (rudimentary visual capacity), unformed visual hallucinations, Riddoch phenomenon (perceive moving targets but not stationary ones); may deny blindness (Anton’s syndrome)

Eye Movements under Supranuclear Control

Horizontal gaze center (Figures 4-10,4-11)

Saccades: contralateral frontal eye fields (frontal lobe) → superior colliculus → pontine paramedian reticular formation (PPRF) → horizontal gaze center (CN 6 nucleus) → ipsilateral lateral rectus l (LR) and contralateral medial rectus (MR) (via MLF)

Smooth pursuit: ipsilateral parieto-occipital lobe → superior colliculus (SC) → PPRF → horizontal gaze center → ipsilateral LR and contralateral MR (via MLF)

Figure 4-10 FEM (voluntary), SEM (pursuit), and SEM (vestibular). Pathways all converge on PPRF for horizontal eye movements. VN, vestibular nuclei.

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Figure 4-11 Composite reminder of the course and lateralization of the 3 conjugate horizontal eye movement pathways.

(From Bajandas FJ, Kline LB: Neuro-ophthalmology Review Manual. Thorofare, NJ, Slack, 1988, p 55.)

Saccadic system

generates fast eye movements (FEM) (refixation); 300-700°/s

Tests: refixation, rotation, calorics, and optokinetic nystagmus (fast saccadic return phase)

Abnormalities: progressive external ophthalmoplegia, myasthenia gravis, Wilson’s disease, Huntington’s disease, ataxia-telangiectasia, spinocerebellar degeneration, progressive supranuclear palsy, olivopontocerebellar atrophy, Whipple’s disease, Gaucher’s disease, MS, Pelizaeus-Merzbacher disease

Ocular motor apraxia: failure to initiate a saccade

Smooth pursuit system

slow eye movements (SEM); following movements; ipsilateral parieto-occipital junction (horizontal); interstitial nucleus of Cajal (vertical)

Tests: Doll’s head, rotation, OKN (pursuit movement)

Abnormalities: demyelination (young patients), microvascular disease (older patients)

Vergence system

maintains foveal fixation on approaching object; controlled by frontal and occipital lobes, and possibly midbrain

Types: voluntary, accommodative, fusional

Test: look from distance to near

Position maintenance system (vestibulo-ocular reflex [VOR])

maintains specific gaze position during head movements

Teleologically oldest eye movement system; also fastest (shortest latency)

Semicircular canals → CN 8 → vestibular nucleus → contralateral horizontal gaze center → EOMs

Test: calorics; rotation

Abnormalities cause oscillopsia

Nonoptic reflex systems

integrate eye movements with body movements

Normal caloric and Doll’s head responses when nuclear and internuclear connections are intact

Calorics: irrigate water into ears and observe induced eye movements; mnemonic COWS (cold opposite, warm same) refers to direction of fast phase of nystagmus in awake patient (jerk nystagmus); in comatose patient, get tonic deviation in opposite direction of mnemonic (sustained slow phase movement only (Figure 4-12))

Bilateral cold water irrigation produces nystagmus with fast phase upward in awake patient and downward tonic deviation in comatose patient; opposite effects with warm water

PATHWAY: vestibular nuclei → contralateral CN 6 nuclei → ipsilateral LR and contralateral MR (via MLF); no connection to the PPRF

Doll’s head (oculocephalic reflex): turn head and observe direction of eye movements; vestibular system moves eyes; use when patient cannot voluntarily move eyes

Eyes should have tonic movement in direction opposite head rotation

INTACT DOLL’S HEAD: supranuclear lesion (cranial nerve pathways to muscles are intact) (i.e. progressive supranuclear palsy)

ABNORMAL DOLL’S HEAD: lesion is infranuclear paresis or restrictive disease (perform forced ductions)

Bell’s phenomenon: upward turning of eyes with forced closure of eyelids

INTACT BELL’S PHENOMENON: supranuclear lesion

Figure 4-12 Vestibulo-ocular reflex demonstrating right beating nystagmus. Right COWS = cold opposite, warm same. (Calorics should be performed with head back 60°.)

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Diplopia

Types

Comitant: amount of deviation same in all fields of gaze

Incomitant: amount of deviation varies in different fields of gaze

Etiology

Monocular: high astigmatism, chalazion or lid mass, corneal abnormality, iris atrophy, polycoria, cataract, subluxed crystalline lens, decentered IOL, posterior capsular opacity, retinal pathology, functional

Binocular: neuropathic (cranial nerve palsies, MS), myopathic (thyroid-related ophthalmopathy, orbital pseudotumor), neuromuscular junction (MG)

Differential diagnosis (DDx)

Supranuclear (due to inadequate convergence): skew deviation, progressive supranuclear palsy, Parkinson’s disease, Huntington’s disease, dorsal midbrain syndrome

Intermittent: MG, MS, migraine, thyroid-related ophthalmopathy, convergence spasm, decompensated phoria, convergence-retraction nystagmus, ocular myotonia

Vertical: MG, MS, thyroid-related, orbital disease (tumor, trauma, inflammation), CN 3 or CN 4 palsy, Brown’s syndrome, skew deviation

Aberrant regeneration: Duane’s syndrome, Marcus Gunn jaw-winking syndrome

Restrictive syndromes

IOP elevation >4 mmHg when eyes directed into restricted field (thyroid, trauma, inflammatory orbital disease, neoplastic process)

Eye Movement Disorders

Central Disorders (Supranuclear) (Figure 4-13)

Often no symptoms or complaints

Figure 4-13 Supranuclear control of eye movements. The pontine horizontal gaze center (blue) and the vertical gaze center in the midbrain (yellow) receive input from the frontal eye fields to initiate saccades, and from the parietal occipital temporal junction to control pursuit. These gaze centers control ocular motility by synapsing upon the ocular motor nerve nuclei (III, IV, and VI).

(From Lavin PJM, Donahue SP: Disorders of supranuclear control of ocular motility. In: Yanoff M, Duker JS (eds) Ophthalmology, 2nd edn. St Louis, Mosby, 2004.)

Horizontal Gaze Palsies

Congenital

Must distinguish between supranuclear and infranuclear causes; often abnormality of CN 6 or interneurons; vertical movements usually unaffected

Möbius’ Syndrome

Horizontal gaze palsy with CN 6, 7, 8, and 9 palsies (facial diplegia, deafness, abnormal digits)

Ocular Motor Apraxia

Saccadic palsy; impairment of voluntary horizontal eye movements with preservation of reflex movements; male > female; congenital or acquired (Balint’s syndrome); extensive bilateral cerebral disease involving supranuclear pathways (usually bilateral frontoparietal); usually benign and resolves in congenital disease

Associations

Gaucher’s disease, spinocerebellar degeneration, MR, ataxia-telangiectasia, Wilson’s disease, hypoplasia of corpus callosum, hydrocephalus; rarely cerebellar mass lesion (perform magnetic resonance imaging [MRI])

Findings

Head thrusting: patient must move head to look at objects; head thrust toward desired direction of gaze results in contralateral slow eye movement so patient must overshoot target; lessens with age; may resolve by age 20; patient may also blink to break fixation

Abnormal OKN: fast phase absent

Abnormal vestibular nystagmus: fast phase absent

Normal pursuits

Normal vertical saccades

Acquired

Frontoparietal lesion (stroke, trauma, or infection)

tonic deviation of eyes to side of lesion (contralateral area 8 unopposed); seizure will move eyes away from lesion

Doll’s head testing and calorics

can turn eyes contralateral to lesion (intact vestibular pathway)

Parieto-occipital lesion

ipsilateral pursuit palsy (cogwheel pursuit)

Parkinson’s disease

reduced blinking, reduced saccades, reduced glabellar reflex suppression, blepharospasm, oculogyric crisis

Huntington’s chorea

Metabolic disorders: hyperglycemia, Wernicke’s encephalopathy, Wilson’s disease

Drug-induced

tricyclic antidepressants, phenytoin, phenothiazines

Pseudogaze palsies

myasthenia gravis, chronic progressive external ophthalmoplegia (CPEO), Duane’s syndrome

Internuclear ophthalmoplegia (INO) (Figure 4-14)

lesion of MLF; inability to adduct ipsilateral eye with nystagmus of fellow eye; may have skew deviation, vertical diplopia, and gaze-evoked, upbeat nystagmus; rule out myasthenia gravis

Unilateral: ischemia (older), demyelination (young patients), tumor, infection (meningitis, encephalitis), trauma, compression

Bilateral (involves both MLF near junction with the 3rd nerve nucleus in midbrain): demyelination / MS (most common), trauma, ischemia, infection, Chiari malformation, toxicity (amitriptyline, ethanol, benzodiazepine)

Types:

ANTERIOR (midbrain): preserved convergence

POSTERIOR (pons): impaired convergence (WEBINO = wall-eyed bilateral INO)

Figure 4-14 1. Right internuclear ophthalmoplegia (INO) 2. Bilateral INO.

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

One-and-a-half syndrome (Fisher syndrome) (Figure 4-15)

lesion of CN 6 nucleus and ipsilateral MLF; causes ipsilateral gaze palsy and INO; only movement is abduction of contralateral eye (with nystagmus); supranuclear lesion therefore convergence intact; called paralytic pontine exotropia when patient appears exotropic; patients with recovery from syndrome may develop oculopalatal myoclonus

Etiology: stroke (most common), MS, basilar artery occlusion, pontine metastases

Figure 4-15 Right acute syndrome (paralytic pontine exotropia).

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Vertical Gaze Abnormalities

Progressive Supranuclear Palsy (Steele-Richardson-Olszewski Syndrome)

Progressive vertical (early) and horizontal (late) gaze palsy (downward gaze usually affected first); no Bell’s phenomenon; doll’s head maneuver gives full range of movement (ROM), indicating supranuclear nature of disorder; eventually frozen globe to all stimuli, spasm of fixation, decreased blink rate, blepharitis, blepharospasm; occasionally, apraxia of eye opening; also, axial rigidity, dysarthria, and dementia

Skew Deviation

Vertical misalignment of visual axes due to imbalance of prenuclear inputs; comitant or incomitant

Vertical tropia, hyperdeviation usually increases on ipsilateral downgaze, no cyclodeviation; hypodeviated eye usually ipsilateral to lesion, except when associated with INO in which hyperdeviated eye is ipsilateral; may occur with other brain stem symptoms or cerebellar disease; MRI of posterior fossa recommended

Etiology

brain stem infarct, MS, increased intracranial pressure (ICP), pseudotumor cerebri, vestibulo-ocular imbalance, cerebellar disease; vertebral–basilar insufficiency may cause transient skew deviation

Treatment

often transient and requires observation only; chronic deviations may be treated with prism spectacles or surgery

Whipple’s Disease

Oculomasticatory myorhythmia (vertical eye movements and facial activity similar to myoclonus)

Olivopontocerebellar Atrophy

Hereditary or sporadic; onset early adulthood; unsteady gait, slurred speech, dementia, optic atrophy, retinal degeneration

Eye movements progressively slow in all directions, finally complete external ophthalmoplegia

Kernicterus

Progressive loss of eye movements

Also, metabolic diseases (maple syrup disease, Wernicke’s encephalopathy), drug-induced

Nystagmus

Rhythmic involuntary oscillations of the eyes due to disorder of SEM system. Direction named after fast phase (brain’s attempt to correct problem), even though abnormality is noted with slow phase

Childhood Nystagmus

Most commonly, congenital, latent, sensory, and spasmus nutans (see Ch. 5, Pediatrics / Strabismus)

Physiologic Nystagmus

Several forms of nystagmus, including end-gaze, optokinetic, caloric, and rotational

Acquired Nystagmus

Pattern helps localize pathology, may have oscillopsia

Bruns’

Combination of gaze-paretic nystagmus when looking toward lesion (fast phase toward the lesion), and vestibular imbalance nystagmus when looking away from lesion (fast phase away from lesion) (i.e., with right-sided lesion: high-amplitude, low-frequency, right-beating nystagmus on right gaze; low-amplitude, high-frequency, left-beating nystagmus on left gaze)

Gaze-paretic component is of high amplitude and low frequency (because of impairment of horizontal gaze mechanism on side of lesion)

Vestibular component is of low amplitude and high frequency, with fast phase away from damaged vestibular nuclei on side of lesion

Due to cerebellopontine angle mass (usually acoustic neuroma or meningioma)

Convergence-Retraction

Cocontraction of lateral recti produces convergence movement (abnormal saccades) on attempted upgaze

Due to periaqueductal gray matter or dorsal midbrain lesion (Parinaud’s syndrome, pinealoma, trauma, brain stem arteriovenous malformation [AVM], MS)

Dissociated

Asymmetric between the 2 eyes (different direction, amplitude, frequency, etc); always pathologic

Due to posterior fossa disease, MS

Downbeat

Eyes drift upward with corrective saccade downward; worsens in downgaze, improves in upgaze; oscillopsia

Due to lesion that affects pathways responsible for downgaze; cervicomedullary junction lesion (Arnold-Chiari malformation, tumor, syrinx: 33%), spinocerebellar degeneration, intoxication, lithium, paraneoplastic cerebellar degeneration, 50% with no identifiable cause

Gaze-Evoked

Nystagmus in direction of gaze, absent in primary position, fast phase toward lesion (cerebellar)

Due to extra-axial mass compressing brain stem (acoustic neuroma, cerebellar hemisphere tumor), intoxication (alcohol or anticonvulsant medications)

If asymmetric, must obtain neuroimaging

Periodic Alternating Nystagmus (PAN)

Changes horizontal direction; jerks right 90 seconds, 5- to 10-second pause, jerks left 90 seconds, repeats; remains horizontal in vertical gaze; usually acquired

Due to disease of vestibulocerebellar system (albinism, cranio-cervico junction lesion [Arnold-Chiari malformation], MS, syphilis, tumor, vascular, dilantin, spinocerebellar degeneration)

Treatment

baclofen; surgery (large recession of all 4 recti muscles)

Seesaw

Vertical and torsional nystagmus with 1 eye rising and intorting while fellow eye falls and excyclotorts, then reverses

Due to suprasellar lesions, CVA, or trauma, or is congenital (craniopharyngioma)

MRI

rule out large parasellar tumors expanding into third ventricle

Upbeat

Eyes drift downward with corrective saccade upward

Due to medullary lesions, midline cerebellar (vermis) lesions, medulloblastoma, cerebellar degeneration, MS

Vestibular

Horizontal, rotary, jerk nystagmus in primary gaze; same in all fields of gaze; slow component is linear; remains horizontal in vertical gaze

Due to vestibular disease, infection (labrynthitis), Ménière’s disease, vascular, trauma, toxicity

Peripheral vestibular disease

fast phase toward good side; slow phase toward lesion; associated with tinnitus, vertigo, deafness; fixation inhibits vertigo and nystagmus; direction of Romberg fall changes with head turning

Voluntary

Unsustainable for longer than 30 seconds; associated with hysteria and malingering

Other Eye Movement Disorders

Ocular Bobbing

Intermittent conjugate rapid downward eye movements followed by slow return to primary position

Often secondary to hemorrhage; patient usually comatose

Ocular Dipping

Opposite of ocular bobbing; intermittent rapid upward eye movements followed by slow return to primary position

Ocular Myoclonus

Vertical pendular nystagmus associated with synchronous palatal (uvula) beating

Due to bilateral pseudohypertrophy of inferior olives in medulla, lesion in myoclonic triangle (red nucleus, ipsilateral inferior olive, contralateral dentate nucleus)

Opsoclonus (Saccadomania)

Rapid, chaotic eye movements in all directions; persists in sleep

Associated with dancing hands and feet

Abnormality of pause cells (normally suppress burst cells of PPRF)

Due to remote, paraneoplastic effect on cerebellum from metastatic neuroblastoma (check urine vanillylmandelic acid [VMA]), occasionally with encephalitis

Waveform

no slow phase; repetitive, random; no intersaccadic interval

Oscillopsia

Illusion of movement in the seen world

Usually occurs in SO myokymia and acquired nystagmus; rarely in congenital nystagmus

Due to vestibulo-ocular reflex abnormality

Cranial Nerve Palsies (FIGURE 4-16)

Oculomotor Nerve (CN 3) Palsy

Anatomy

nucleus in rostral midbrain; fascicle travels ventrally through midbrain, traversing red nucleus and corticospinal tract in cerebral peduncle; nerve enters subarachnoid space, passes between posterior cerebral and superior cerebellar arteries, then courses lateral to posterior communicating artery and enters lateral wall of cavernous sinus; receives sympathetics from internal carotid plexus; passes through superior orbital fissure and divides into superior (supplies SR and levator) and inferior (supplies IR, MR, IO, iris sphincter, and ciliary muscle) divisions.

Figure 4-16 Cranial nerve pathways.

(Copyright Peter K. Kaiser, MD.)

Only 1 subnucleus (midline location) supplies both levator palpebrae superioris; fibers from superior rectus (SR) subnucleus supply contralateral SR; Edinger-Westphal nucleus supplies both pupils (Figure 4-18)

Figure 4-18 Anatomy of the 3rd nerve nucleus. The 3rd nerve nucleus consists of a single, central, caudally located nucleus for the levator palpebrae, paired bilateral subnuclei with crossed projections that innervate the superior recti, and paired bilateral subnuclei with uncrossed projections that innervate the medial recti, inferior recti, and inferior oblique muscles. Parasympathetic input to the ciliary body and iris sphincter arises from the Edinger-Westphal nucleus.

(Redrawn from Warwick R: Representation of the extraocular muscles in the oculomotor nuclei of the monkey. J Comp Neurol 98:449–503,1953.)

Findings

ptosis, hypotropia, exotropia; may involve pupil (fixed and dilated); may cause pain

7 syndromes (Figure 4-17)

Nuclear CN 3 palsy (Figure 4-17,

): extremely rare; contralateral SR paresis and bilateral ptosis; pupil involvement is both or neither

Fascicle syndromes (see Figure 4-17,

): ischemic, infiltrative (tumor), or inflammatory (rare)

NOTHNAGEL’S SYNDROME: lesion of fascicle and superior cerebellar peduncle that causes ipsilateral CN 3 paresis and cerebellar ataxia

BENEDIKT’S SYNDROME: lesion of fascicle and red nucleus that causes ipsilateral CN 3 paresis, contralateral hemitremor (resting and intentional), and contralateral decreased sensation

WEBER’S SYNDROME: lesion of fascicle and pyramidal tract that causes ipsilateral CN 3 paresis and contralateral hemiparesis

CLAUDE’S SYNDROME: combination of Nothnagel’s and Benedikt’s syndromes

Uncal herniation (see Figure 4-17,

): supratentorial mass may cause uncal herniation compressing CN 3

Posterior communicating artery (PCom or PCA) aneurysm (see Figure 4-17,

): most common nontraumatic, isolated, pupil involving CN 3 palsy; aneurysm at junction of PCom and carotid artery compresses nerve, particularly external parasympathetic pupillomotor fibers; usually painful

Cavernous sinus syndrome (see Figure 4-17,

): associated with multiple CN palsies (3, 4, V₁, 6) and Horner’s; CN 3 palsy often partial and pupil sparing; may lead to aberrant regeneration

Orbital syndrome (see Figure 4-17,

): tumor, trauma, pseudotumor, or cellulitis; associated with multiple CN palsies (3, 4, V₁, 6), proptosis, chemosis, injection; ON can appear normal, swollen, or atrophic

After passing through the superior orbital fissure, CN 3 splits into superior and inferior divisions; therefore, CN 3 palsies distal to this point may be complete or partial

Pupil-sparing isolated CN 3 palsy (see Figure 4-17,

): small-caliber parasympathetic pupillomotor fibers travel in outer layers of nerve closer to blood supply (but more susceptible to damage by compression); fibers at core of nerve are compromised by ischemia; may explain pupil sparing in 80% of ischemic CN 3 palsies and pupil involved in 95% of compressive CN 3 palsies (trauma, tumor, aneurysm)

ETIOLOGY:

ADULTS: vasculopathic / ischemic (diabetes mellitus [DM], hypertension [HTN]), trauma, giant cell arteritis (CGA), occasionally tumor, aneurysm (very rare)

CHILDREN: congenital, trauma, tumor, aneurysm, migraine

14% of PCom aneurysms initially spare pupil

20% of diabetic CN 3 palsies involve pupil

Microvascular CN 3 palsies usually resolve in 3 to 4 months

Myasthenia gravis may mimic CN 3 palsy

Figure 4-17 Seven syndromes of CN 3 palsy.

(Copyright Peter K. Kaiser, MD.)

Workup

If < age 11: MRI / MRA

If aged 11–50: MRI / MRA and medical workup

If > age 50:

WITH PUPIL INVOLVEMENT: MRI / MRA; if normal, cerebral angiography (catheter)

WITH PUPIL SPARING: usually microvascular; no invasive investigation needed initially; check BP (HTN), blood glucose (DM), ESR, C-reactive protein (giant cell arteritis), complete blood count (CBC), antinuclear antibody (ANA), Venereal Disease Research Laboratory (VDRL), fluorescent treponemal antibody absorption (FTA-ABS); if it persists >3 months, MRI / MRA (magnetic resonance angiography) with cerebral angiography (aneurysm) if negative

Trochlear Nerve (CN 4) Palsy

Anatomy

nucleus in caudal mesencephalon at level of inferior colliculus; decussates in anterior medullary velum next to aqueduct of Sylvius; fascicle passes between posterior cerebral artery and superior cerebellar artery; nerve travels in lateral wall of cavernous sinus, enters orbit via superior orbital fissure outside annulus of Zinn; innervates superior oblique muscle

Longest intracranial course (75 mm); only CN that exits dorsally from brain stem; only CN that decussates (except for CN 3 subnucleus that innervates SR); most commonly injured CN following closed head injury (owing to long course)

Etiology

congenital (most common in kids); in adults: 40% trauma, 30% ischemia, 20% miscellaneous or undetermined, 10% aneurysm

Findings

ipsilateral hypertropia (due to superior rectus overaction)

5 syndromes (Figure 4-19)

Nuclear / fascicular syndrome (see Figure 4-19,

): hemorrhage, infarction, demyelination, trauma; may have contralateral Horner’s or INO

Subarachnoid space syndrome (see Figure 4-19,

): injury as nerve emerges from dorsal surface of brain stem; trauma (contracoup forces transmitted to brain stem by free tentorial edge), tumor (pinealoma, tentorial meningioma), meningitis, neurosurgical trauma

Cavernous sinus syndrome (see Figure 4-19,

): multiple CN palsies (3, 4, V₁, 6) and Horner’s

Orbital syndrome (see Figure 4-19,

): multiple CN palsies (3, 4, V₁, 6) and Horner’s; proptosis, chemosis, injection

Isolated CN 4 palsy (see Figure 4-19,

CONGENITAL: most common; may occur in elderly due to decompensation; large, vertical fusion amplitudes (10–15 Δ); check old photos for head tilt

ACQUIRED: acute onset of vertical diplopia; head position (chin down, face turn to opposite side, head tilt to opposite shoulder)

Figure 4-19 5 syndromes of CN 4 palsy.

(Copyright Peter K. Kaiser, MD.)

DDx of vertical diplopia

myasthenia gravis, thyroid-related ophthalmopathy, orbital disease (tumor, trauma, inflammation), CN 3 palsy, CN 4 palsy, Brown’s syndrome, skew deviation, MS

Diagnosis

Parks-Bielschowsky 3-step test (used for hypertropia due to weakness of a single muscle)

Step 1: Which eye is hypertopic?

LEFT HYPER: paresis of OD elevators (RSR or RIO) or OS (oculus sinister, left eye) depressors (LIR or LSO)

Step 3: Worse on right or left head tilt?

With head tilt, eyes undergo corrective torsion (with right head tilt, OD intorts and OS extorts)

If 1 of the intorters is the cause of the hyper, then tilting head will worsen hyper on side of head tilt

If worse hyper on left head tilt, problem with left intorters (LSR, LSO) or right extorters (RIR, RIO)

Bilateral CN 4 palsies

usually due to severe head trauma (contusion of anterior medullary velum)

Vertical deviation in primary gaze may or may not be present

RHT in left gaze; LHT in right gaze

Either eye can be hyper on step 3 of 3-step test

V-pattern esotropia (ET >25 Δ)

>10° of torsion with double Maddox rod test

Workup

check BP, blood glucose, CBC, ESR, VDRL, FTA-ABS, ANA; neuroimaging if history of head trauma or cancer, signs of meningitis, young age, other neurologic findings, or isolated palsy that does not improve after 3–4 months

Treatment

Glasses: occlude lens or prisms for diplopia

Muscle surgery:

KNAPP’S PRINCIPLES FOR CN 4 PALSY: strengthen (tuck) the palsied SO, weaken the antagonist (ipsilateral IO), or weaken the yoke (contralateral IR) to correct hyperdeviation

HARADA-ITO PROCEDURE: anterior and lateral displacement of palsied muscle to correct excyclotorsion

Abducens Nerve (CN 6) Palsy

Anatomy

nucleus in dorsal pons medial to CN 7; travels anterior and lateral to PPRF, then through pyramidal tract, and exits lower pons in pontomedullary groove in subarachnoid space; climbs over clivus (vulnerable to elevated ICP) over petrous ridge, along base of skull, through Dorello’s canal, under Gruber’s ligament; enters cavernous sinus and then orbit through superior orbital fissure; passes laterally to supply lateral rectus

Second most common CN to be injured following closed head injury

CN 6 lesions occur in conditions that cause increased ICP

6 syndromes (Figure 4-20)

Brain stem syndromes (see Figure 4-20,

MILLARD-GUBLER SYNDROME: lesion of CN 6 and 7 fascicles and pyramidal tract causing CN 6 and 7 palsies with contralateral hemiparesis

RAYMOND’S SYNDROME: lesion of CN 6 and pyramidal tract causing CN 6 palsy and contralateral hemiparesis

FOVILLE’S SYNDROME: lesion of CN 6 nucleus, CN 5 and 7 fascicles, and sympathetics causing ipsilateral 5, 6, and 7 palsies, horizontal conjugate gaze palsy, and ipsilateral Horner’s

MÖBIUS’ SYNDROME: associated with CN 7 lesion, supernumerary digits, skeletal abnormalities, mental retardation

Subarachnoid space syndrome (see Figure 4-20,

): increased ICP can cause downward displacement of brain stem with stretching of CN 6 (tethered at exit from pons and Dorello’s canal); occurs in 30% of patients with pseudotumor cerebri; also hemorrhage, meningitis, inflammation (sarcoidosis), infiltration (lymphoma, leukemia, carcinoma)

Petrous apex syndrome (see Figure 4-20,

): portion of CN 6 within Dorello’s canal is in contact with tip of petrous pyramid and is susceptible to processes affecting the petrous bone

GRADENIGO’S SYNDROME: localized inflammation or extradural abscess of petrous apex (mastoiditis) following otitis media; CN 6 palsy with ipsilateral decreased hearing, facial pain, and facial paralysis

PSEUDO-GRADENIGO’S SYNDROME: various etiologies:

NASOPHARYNGEAL CA: obstruction of Eustachian tube can cause serous otitis media, can invade cavernous sinus causing CN 6 palsy

CEREBELLOPONTINE ANGLE TUMOR: CN 5, 6, and 7 palsies; decreased hearing, papilledema

PETROUS BONE FRACTURE: may have CN 5, 6, 7, or 8 lesions, hemotympanum, Battle’s sign (bruising over mastoid bone), CSF otorrhea

BASILAR ANEURYSM

CLIVUS CHORDOMA

Cavernous sinus syndrome (see Figure 4-20,

ETIOLOGY: trauma, vascular (diabetes, migraine, aneurysms, arteriovenous [AV] fistula), tumor, inflammation, granuloma

FINDINGS: CN 3, 4, V₁, Horner’s, ON, chiasm, and pituitary involvement

Orbital syndrome (see Figure 4-20,

ETIOLOGY: trauma, tumor, orbital pseudotumor, cellulitis

FINDINGS: proptosis, chemosis, conjunctival injection; may have ON edema or atrophy; CN V₁ may be involved

Isolated CN 6 palsy (see Figure 4-20,

CHILDREN: often postviral (resolves over weeks), associated with otitis media; consider tumor (pontine glioma), trauma

ADULTS: vasculopathic, undetermined, MS, tumor (nasopharyngeal CA, cavernous sinus meningioma, chordoma), trauma, temporal arteritis, syphilis

Figure 4-20 6 syndromes of CN 6 palsy.

(Copyright Peter K. Kaiser, MD.)

Pseudo–CN 6 palsy

Workup

Congenital: usually resolves by 6 weeks

Acquired: same as for CN 4 palsy; consider lumbar puncture (LP) and Tensilon test

Trigeminal Nerve (CN 5) Palsy

Trigeminal neuralgia (tic douloureux)

due to compression of CN 5 at root (superior cerebellar artery aneurysm or tumor); facial pain involves entire CN 5 division; lasts seconds; 95% unilateral; usually involves maxillary or mandibular distribution, ophthalmic distribution alone is rare

Diagnosis

neuroimaging

Treatment

medical (carbamazepine) or surgical (radiofrequency destruction of trigeminal ganglion through foramen ovale)

Facial Nerve (CN 7) Palsy

Anatomy

passes around CN 6 nucleus; exits brain stem ventrally at cerebellopontine angle; enters internal auditory canal (of petrous portion of temporal bone) with nervus intermedius and cochlear and vestibular nerves; enters facial nerve canal; exits temporal bone via stylomastoid foramen; branches in parotid gland. Supplies facial muscles and lacrimal and salivary glands; posterior of tongue; external ear sensation; dampens stapedius

Lacrimal gland innervation (parasympathetic): originates in superior salivatory nucleus, fibers leave brain with nervus intermedius (glossopalatine) and travel with CN 7 through geniculate ganglion, emerges from petrous portion of sphenoid bone as greater superficial petrosal nerve; enters pterygoid canal and enters sphenopalatine ganglion, where primary parasympathetic fibers synapse and second-order fibers join zygomatic nerve, which sends a branch to lacrimal gland.

Frontal lobe (precentral motor cortex) provides input to CN 7 nuclei in pons (control voluntary facial movements); upper face innervation is bilateral (from both supranuclear motor areas), lower face innervation is mainly from contralateral supranuclear motor area (Figure 4-23)

Figure 4-23 Facial weakness due to upper and lower motor neuron lesions.

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Supranuclear palsy

lesion in precentral gyrus of cerebral cortex results in contralateral paralysis of volitional facial movement involving lower face more severely than upper

Emotional and reflex movements (smiling, spontaneous blinking) are preserved (extrapyramidal)

Brain stem lesion (pons)

ipsilateral facial weakness involving both upper and lower face; due to tumor, vascular causes

Associated with CN 5 and 6 palsies, lateral gaze palsy, cerebellar ataxia, and contralateral hemiparesis

With CN 5 palsy: cerebellopontine angle tumors, infratemporal fossa tumors

With CN 6 palsy: brain stem injury or injury near anteromedial portion of temporal bone (Gradenigo’s syndrome)

Peripheral CN 7 lesion

acute unilateral facial nerve palsy is most common cranial neuropathy

Bell’s palsy: idiopathic facial nerve palsy; may be preceded by preauricular or mastoid pain

Facial weakness progressing to paralysis over months

Associated with progressive twitching or facial spasm; suggests neoplasm; most common between ages 15 and 45; 10% have positive family history

TREATMENT: consider oral steroids

PROGNOSIS: 70% have complete recovery in 6 weeks; 85% will fully recover; 10% recurrence (ipsilateral or contralateral)

POOR PROGNOSTIC SIGNS: complete facial paralysis at presentation, impairment of lacrimation, advanced age; if incomplete recovery, aberrant regeneration is common

Trauma: fracture of temporal bone

FINDINGS: hearing loss, vertigo, hemotympanum, perforated tympanic membrane, Battle’s sign (bruising over mastoid bone)

Delayed onset or incomplete paralysis usually due to nerve contusion or swelling

Complete facial paralysis immediately after head trauma suggests nerve transection

BIRTH TRAUMA WITH FORCEPS: congenital CN 7 lesion; tends to resolve

Infection:

RAMSAY-HUNT SYNDROME: herpes zoster virus (HZV) oticus (infection of outer ear and nerves of inner auditory canal); 20% have sensorineual hearing loss and dizziness

Preauricular or mastoid pain precedes facial paralysis by 1–3 days; associated with a vesicular rash of outer ear or on tympanic membrane

TREATMENT: acyclovir and prednisone

PROGNOSIS: poor; only 10% recovery in patients with complete paralysis; 66% recovery with partial paralysis

May develop postherpetic neuralgia

Also HIV, Lyme disease, otitis media, malignant otitis externa (usually elderly diabetics; can progress to cellulitis of inner ear canal and osteomyelitis of temporal bone; usually caused by Pseudomonas)

Sarcoidosis: most frequent cause of bilateral 7th due to infiltration of CN 7, usually at parotid gland

Erosive cholesteatoma: pressure on segment of CN 7 that travels through middle ear

Tumor: most intracranial and bone tumors that cause facial paralysis are benign (including acoustic neuroma, meningioma, glomus tumors [triad of facial paralysis, pulsatile tinnitus, and hearing loss]); tumors of parotid gland are usually malignant (adenoid cystic carcinoma)

Guillain-Barré syndrome (Miller Fisher variant): facial diplegia can occur with ophthalmoplegia and ataxia; absent deep tendon reflexes; CSF protein elevated with normal cell count; often bilateral

Melkersson-Rosenthal syndrome: recurrent facial paralysis with chronic facial swelling and lingua plicata (furrowing of tongue); unilateral or bilateral; occurs in childhood or adolescence

Aberrant facial innervation:

MARCUS-GUNN JAW WINKING: activation of muscles of mastication induces orbicularis oculi contraction

CROCODILE TEARS: lacrimation evoked by chewing

Other findings

lacrimation (damage to greater superficial petrosal nerve), impaired stapedius muscle reflex (damage to stapedial nerve), impaired taste (damage to chorda tympani nerve), swelling of parotid gland or cervical lymphatics (suggests malignant tumor or inflammatory condition of parotid [sarcoidosis, TB])

Disorders of CN 7 overactivity

Benign essential blepharospasm: frequent bilateral blinking proceeds to involuntary spasms and forceful contractures of orbicularis; may cause functional blindness; unknown etiology; usually affects women over age 50; absent during sleep

TREATMENT: botulinum toxin (Botox) injections, rarely surgery (orbicularis myomectomy)

Hemifacial spasm: unilateral contractions of facial muscles; usually due to vascular compression of CN 7 at brain stem; rarely caused by tumor; present during sleep; obtain MRI

Facial myokymia: fasciculations of facial muscles; if multifocal and progressive, consider MS

Eyelid myokymia: benign fasciculations of eyelid

Multiple CN Palsies

CN 3, 4, and 5

due to lesion of brain stem, cavernous sinus (Figure 4-24), and / or superior orbital fissure

DDx: AV fistula, cavernous sinus thrombosis, metastases to cavernous sinus, skin malignancy with perineural spread to cavernous sinus, meningioma, mucormycosis, HZV, Tolosa-Hunt syndrome, mucocele, nasopharyngeal CA, carcinomatous meningitis, pituitary apoplexy (headache with bilateral signs and decreased vision)

Figure 4-24 Anatomy of the cavernous sinus.

(From Moster M: Paresis of isolated and multiple cranial nerves and painful ophthalmoplegia. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Herpes zoster ophthalmicus

CN 3, 4, and 6 palsies occur in about 15%; pain and skin eruption in trigeminal distribution, decreased corneal sensation, pupil may be involved (tonic pupil)

Hutchinson’s rule: if tip of nose involved (nasociliary nerve), eye will probably (but not always) be involved

Mimics of multiple cranial nerve palsies: MG, CPEO, orbital lesions (thyroid, pseudotumor, tumor), progressive supranuclear palsy, Guillain-Barré syndrome

Pupils

Innervation (Figure 4-25)

Iris Sphincter

Parasympathetic innervation from Edinger-Westphal nucleus

Figure 4-25 Parasympathetic and sympathetic innervation of the iris muscles.

(From Kardon RH: The pupils. In: Yanoff M, Duker JS (eds) Ophthalmology, 2nd edn. St Louis, Mosby, 2004.)

Pathway of pupillary light reflex

optic nerve → chiasm (fibers split) → optic tract → pretectal nucleus (synapse) → cross to both EW nuclei (synapse) → travel via CN 3 though subarachnoid space and cavernous sinus, then travel in inferior division of CN 3 to ciliary ganglion → postganglionic fibers travel via short ciliary nerves to ciliary body and iris sphincter

Iris Dilator

Sympathetic innervation

Pathway

posterior hypothalamus → down spinal cord → synapse in ciliospinal center of Budge (C8–T2 level) → second-order neuron ascends sympathetic chain → over apex of lung → synapse at superior cervical ganglion → third-order neuron ascends with ICA and joins CN 6 in cavernous sinus → enters orbit via long ciliary nerve (through superior orbital fissure next to CN V₁) to iris dilator and Müller’s muscle

syphilis (Argyll-Robertson), Adie’s pupil, familial dysautonomia (Riley-Day syndrome), Parinaud’s syndrome, RAPD, physiologic, severe retinal disease, aberrant regeneration of CN 3, diabetes, myotonic dystrophy, encephalitis, alcoholism, herpes zoster ophthalmicus (HZO)

Abnormal Light and Near Response

Pharmacologic, trauma, CN 3 palsy

Horner’s Syndrome

Sympathetic lesion causing ptosis, miosis, and anhidrosis; anhidrosis often present in both first- and second-order lesions; may also have facial numbness, diplopia, and vertigo; may have mild inverse ptosis of lower lid, dilation lag; anisocoria most pronounced in dim light; congenital (forceps injury, shoulder dystocia); can cause iris heterochromia (ipsilateral lighter iris)

Preganglionic

from hypothalamus to superior cervical ganglion

First-order neuron (central Horner’s): hypothalamus to spinal cord level C8-T2 (ciliospinal center of Budge)

ETIOLOGY:

MIDBRAIN: neuron located near CN 4 nucleus in dorsolateral tegmentum; lesion at this level (usually ischemia) causes Horner’s and superior oblique palsy

PONS: near CN 6 nucleus; ischemia, tumor, demyelination, polio, syringomyelia, and inflammation, Foville’s syndrome (lesion of CN 5, 6, and 7 and Horner’s)

MEDULLA: lateral medullary syndrome of Wallenberg (stroke of vertebral artery or PICA causing lateral medullary infarction; ipsilateral lesion of CN 9, 10, and 11; Horner’s, vertigo, cerebellar signs, skew deviation, ipsilateral decreased pain / temperature sensation of face, contralateral decreased pain/temperature sensation of trunk and limbs); no extremity weakness

VERTEBROBASILAR STROKES AND VERTEBRAL ARTERY DISSECTION

CERVICAL DISC DISEASE: arthritis, demyelination, inflammation, tumors

SYRINGOMYELIA: spinal cord cavities surrounded by gliosis involving spinothalamic tracts; causes ipsilateral loss of pain / temperature sensation but preservation of touch; muscle wasting and weakness (especially small hand muscles); Charcot’s arthropathy (35%)

Second-order neuron: majority of preganglionic Horner’s; ciliospinal center of Budge to superior cervical ganglion

ETIOLOGY: mediastinal or apical tumor (neuroblastoma [most common], Pancoast’s), thyroid disease, neurofibroma, pneumothorax, cervical infections, upper respiratory tract tumors, brachial plexus syndromes, carotid artery dissection, aneurysm, trauma

Unilateral dilated, poorly reactive pupil in comatose patient due to ipsilateral supratentorial mass causing displacement of hippocampal gyrus (uncal herniation) entrapping CN 3; pupillomotor fibers travel in peripheral portion of nerve and are susceptible to early damage from compression

Simple Anisocoria

Most common cause of relative difference (<1 mm) between pupils; occurs in up to 20% of general population

Ocular Muscle Disorders

Weakness of voluntary muscles due to autoimmunity to motor end plates (antibodies block ACh receptors), hallmark is fatigability; 90% have eye symptoms, 50% present with eye symptoms; females > males; onset aged 15-50; 80% with ocular presentation will develop generalized disease; 15% spontaneously resolve; does not affect pupillary fibers

asymmetric ptosis, seesaw ptosis (‘curtaining’; when more ptotic lid is lifted, other lid falls owing to Hering’s law), Cogan’s lid twitch (when patient looks from downgaze to primary position, lid will overshoot), facial muscle weakness, ophthalmoplegia, pseudo-INO, nystagmus (on extreme gaze)

Other findings

jaw weakness, dysphagia, dysarthria, dyspnea, muscle bulk usually preserved until late

DDx

Myotonic dystrophy, CPEO, involutional ptosis, toxins (snake, arthropod, bacteria [botulism])

Eaton-Lambert syndrome: paraneoplastic syndrome consisting of profound proximal muscle pain and weakness, dysarthria, dysphagia; associated with small cell lung cancer

MECHANISM: impaired presynaptic release of ACh; 50% demonstrate specific antibodies against presynaptic voltage-gated calcium channels

DIAGNOSIS: muscle strength and reflexes are enhanced with exercise; no improvement with edrophonium

EMG: increased muscle action potentials with repeated nerve stimulation

Diagnosis

Tensilon test (edrophonium [IV]; AChE inhibitor that prolongs action of ACh, resulting in stronger muscle contraction): positive 80–90% of the time, but high false-negative rate; may cause bradycardia – therefore, give test dose of 1–2 mg first; other adverse effects include sweating, nausea, vomiting, salivation, fever, elevated IOP; antidote is atropine sulfate (0.5 mg); alternative test is neostigmine methylsulfate (Prostigmine [IM]: useful in children and adults without ptosis, requires longer observation period [20–45 minutes])

ACh receptor antibody: 3 types (binding Ab, blocking Ab, modulating Ab); 50% sensitive in ocular MG, 80% sensitive in general MG, 90% positive in MG with thymoma, 99% specific; seronegative MG due to antigen excess, ocular-specific Ab; Ab against other components of ACh receptor

EMG: fatigue with repetitive nerve stimulation; single-fiber EMG is best

Photos: check old photos; morning versus evening for variability in lid position

Rest test: rest with eyes closed for 30 minutes; positive if improvement in ptosis occurs

Ice test: neuromuscular transmission improves in cold; therefore, apply ice pack for 2 minutes; positive if improvement occurs

Others: chest CT / MRI, thyroid function and lupus tests

Treatment

pyridostigmine (Mestinon [AChE inhibitor]), steroids, plasmapheresis, IV gamma globulin, cyclosporine (ciclosporin), azothioprine, thymectomy (33% resolve, 33% improve, 33% no benefit); prism spectacles and consider surgery for stable strabismus (>6–12 months)

Eye Movements In Coma

Water irrigated into ear produces nystagmus; direction of nystagmus (fast phase) is COWS (cold opposite, warm same); jerk nystagmus in awake patient; tonic deviation in comatose patient in opposite direction of mnemonic; bilateral cold water irrigation produces upbeat nystagmus in awake patient; downward tonic deviation in comatose patient

Optic Nerve

Developmental Anomalies

(See Ch. 5, Pediatrics / Strabismus.)

Optic Disc Swelling

Nerve fibers anterior to lamina cribrosa swell due to obstruction of axoplasmic flow at level of lamina choroidalis or lamina scleralis

Orthograde transport (ganglion cells to LGB): slow component = 2 mm/day; fast component = 500 mm/day

Retrograde transport (LGB to ganglion cells)

Mechanism

ischemia, inflammation, increased intracranial pressure, compression

Findings

elevated hyperemic nerve head (3 diopters = 1 mm), blurred disc margins, loss of physiologic cup, peripapillary NFL edema, chorioretinal folds, dilated / tortuous veins, peripapillary flame-shaped hemorrhages, exudates, cotton wool spots (nerve fiber layer [NFL] infarcts)

Chronic swelling may cause Paton’s lines (radial or concentric folds of peripapillary retina), gliosis, high water marks, pale disc, disc pseudodrusen, attenuated vessels, vision loss

DDx of optic disc edema / pseudoedema

papilledema, ischemic optic neuropathy, optic neuritis, central retinal vein occlusion (CRVO), diabetic papillitis, malignant hypertension, neuroretinitis (cat-scratch disease), infiltration of the optic disc (sarcoidosis, tuberculosis, leukemia, metastases), optic disc drusen, optic nerve head tumors (astrocytic hamartoma, gliomas, capillary hemangioma), orbital disease / compressive optic neuropathy (thyroid-related ophthalmopathy, orbital pseudotumor, orbital mass), inflammatory diseases (syphilis, acute posterior multifocal placoid pigment epitheliopathy [APMPPE], Vogt-Koyanagi-Harada [VKH] syndrome), Leber’s hereditary optic neuropathy

Papilledema

Disc edema due to increased intracranial pressure

Findings

disc edema (may be asymmetric); loss of spontaneous venous pulsations (absent in 20% of normals); transient visual obscurations (visual blackouts lasting <10 seconds associated with postural changes); diplopia (due to unilateral or bilateral CN 6 palsies); normal color vision, acuity, and pupils; enlarged blind spot on VF; headache, nausea, vomiting

Chronic cases: pale atrophic nerve, arteriolar attenuation, poor vision, VF loss, refractile small hyaline bodies on the disk

headache, nausea, vomiting, optic disc edema (may be asymmetric), transient visual obscurations, photopsias, VF defect (enlarged blind spot, constriction, or arcuate scotoma), retrobulbar pain, pulsatile intracranial noises; may have visual loss, positive RAPD, diplopia (CN 6 palsy)

In children: irritability; no disc swelling if fontanelles open

Associations

endocrine disorder (Addison’s; steroid withdrawal), chronic obstructive lung disease, thrombosis of dural sinus (trauma, childbirth, middle ear infection, hypercoagulable state); use of steroids, birth control pills, vitamin A, tetracycline, nalidixic acid, isotretinoin; may be exacerbated with pregnancy

Advanced VF loss: ON sheath decompression, serial lumbar punctures (temporary relief), lumbar–peritoneal shunt

Optic Neuritis

Inflammation of optic nerve; idiopathic or associated with systemic disease; most common optic neuropathy in people <45 years old; female preponderance

Findings

acute unilateral visual loss (can evolve over 1st week, then spontaneous improvement over weeks [70% regain 20/20]), ocular pain exacerbated by eye movements, decreased color vision and contrast sensitivity, positive RAPD, VF defect (50% diffuse, 20% central scotoma, rarely altitudinal), optic nerve appears normal or swollen (35%), disc pallor late

Other findings

Pulfrich phenomenon: motion of pendulum appears elliptical owing to altered depth perception from delayed conduction in the demyelinated nerve

Uhthoff’s symptom: worsening of symptoms with heat or exercise; present in 50% after recovery

Phosphenes: flashes of light induced by eye movements or sound

Auditory clicks: CN 7 innervates stapedius, and patient hears click with effective transmission

1 IV steroids: 250 mg IV methylprednisolone qid × 3 days, followed by oral prednisone (1 mg/kg/day) × 11 days

2 Oral steroids: prednisone (1 mg/kg/day) × 14 days

3 Oral placebo: 14 days

Results

IV steroids: more rapid recovery of visual acuity at 2 weeks; did not reduce risk of subsequent attacks; decreased incidence of MS at 2 years vs placebo, but no difference at 3 years

Oral prednisone: associated with higher rate of new attacks in either eye at 1 year; highest relapse rate of optic neuritis at 5 years (41% vs 25% for IV and placebo groups)

Brain MRI: periventricular white matter lesions were associated with MS

Lesions in 50% of patients with first attack of optic neuritis

5-YEAR RESULTS: 30% risk of developing MS regardless of treatment group

WITH NO LESIONS: 16% developed MS

3 OR MORE LESIONS: 51% developed MS

Increased risk of developing MS if previous neurologic symptoms (regardless of MRI status)

10-YEAR RESULTS:

WITH NO LESIONS: 22% developed MS

WITH ³1 LESION: 56% developed MS

If normal MRI, no previous neurologic findings or fellow eye involvement: decreased risk of MS if optic neuritis was painless, if disc swelling was present and vision loss was only mild

No patients developed MS who had normal MRI with peripapillary hemorrhage or macular exudates

Abnormal MRI: 43% progress to MS by 3 years; progression to MS at 1 year was 7.5% with IV steroids, 14.7% with oral steroids, and 16.7% with placebo

Conclusions

In general, about 30% develop MS within 4 years and 38% develop MS by 10 years (risk is higher in women than men)

Consider treating optic neuritis with IV steroids; do not initiate treatment with oral steroids

Regardless of MRI status, there is a higher risk of developing MS if the patient has previous neurologic symptoms or a history of optic neuritis in the fellow eye

Other findings: scalp tenderness, jaw or tongue claudication, polymyalgia rheumatica (PMR), fever, malaise, anorexia, weight loss, anemia, headache, tender temporal artery, neck pain, brain stem stroke (due to involvement of vertebral artery); cotton wool spots, choroidal ischemia (seen as patchy choroidal filling on fluorescein angiography (FA))

Pathology: granulomatous inflammation with epithelioid cells, lymphocytes, giant cells; disruption of internal elastic lamina and proliferation of intima with aneurysm formation (Figure 4-26)

Diagnosis: elevated ESR (for men > [age/2]; for women > [(age +10)/2]; may be normal in 10%), C-reactive protein (above 2.45 mg/dL), low hematocrit (anemia of chronic illness), FA (patchy choroidal filling, nonperfusion), temporal artery biopsy (inflammation in artery wall with disruption of internal elastica lamina, skip lesions [specimen at least 3 cm], perform within 2 weeks of steroid treatment)

Treatment (emergent): steroids (prednisone 60–120 mg orally; consider IV initially [1 g for 3 days]) to prevent fellow eye involvement (65% risk of involvement of fellow eye without treatment; usually affected within 10 days); some patients lose vision despite treatment

Figure 4-26 Arteric AION demonstrating vasculitis of all coats of temporal artery with giant cells.

(Courtesy of MM Rodrigues. From Yanoff M, Fine BS 2002 Ocular Pathology, 5th edn. Mosby, St Louis.)

Nonarteritic (NAION) (ischemic)

no associated symptoms; usually aged 50–75 years; associated with microvascular disease (diabetes, hypertension) and collagen vascular disorders; recurrence in same eye is rare; 25–40% risk of fellow eye involvement; normal ESR; NAION may be mimicked by amiodarone and phosphodiesterase-5 inhibitors

Treatment: none

ISCHEMIC OPTIC NEUROPATHY DECOMPRESSION TRIAL (IONDT): optic nerve sheath fenestration is not effective

Smokers had earlier mean onset (age 64) than nonsmokers (age 70)

43% of control patients regained 3 or more lines of vision at 6 months (vs 34% of those having surgery)

Surgery had higher risk of loss of 3 lines of vision (24% vs 12% with observation)

Pseudo Foster-Kennedy syndrome

AION is the most frequent cause of unilateral disc edema and contralateral optic atrophy; disc not hyperemic like true Foster-Kennedy syndrome

Retrobulbar Optic Neuropathy (Posterior Ischemic Optic Neuropathy)

Rare; usually bilateral; occurs with severe anemia and hypotension (i.e. major blood loss from surgery, trauma, GI bleed, dialysis); associated with medications (antibiotics [ethambutol, isoniazid, sulfonamides, chloramphenicol], anticancer drugs [cisplatin, vincristine, busulfan])

slow progressive vision loss, decreased color vision, positive RAPD, VF defect (central scotoma that extends to periphery), proptosis; disc may be normal, pale, or swollen; may have endocrine abnormalities (parachiasmal lesions), chemosis and restricted motility (thyroid)

Chiasm Compression

Pituitary Tumor

Most commonly chromophobe (often prolactinoma); can also secrete adrenocorticotropin (ACTH) (Cushing’s disease); basophil can secrete ACTH; eosinophil can secrete growth hormone (GH) (acromegaly); secreting tumors usually present with endocrine dysfunction, except prolactin-secreting tumor in males (presents with signs of chiasmal compression); 30% nonsecreting (present with vision loss)

Retrochiasmal Disorders

Cause homonymous VF defects (see Figure 4-9)

Cogan’s Dictum

causes homonymous hemianopia

With asymmetric OKN = parietal lobe lesion (usually mass)

With symmetric OKN = occipital lobe lesion (usually infarction)

affect fibers from superior retina first (contralateral inferior homonymous quadrantanopia) or contralateral inferior homonymous hemianopia denser inferiorly; spasticity of conjugate gaze (tonic deviation of eyes to opposite side of parietal lesion); OKN asymmetry (nystagmus dampened when stimuli moved in direction of damaged parietal lobe); may have contralateral motor paresis

Temporal crescent: homonymous hemianopia with sparing of far temporal periphery (supplied by nasal retina and travels to most anterior portion of mesial surface of contralateral occipital lobe)

Other findings

unformed visual hallucinations, paliopia (perseveration in homonymous field), prosopagnosia (inability to recognize faces; bilateral medial occipitotemporal lesion), Riddoch phenomenon (ability to perceive moving objects but not stationary ones)

Disconnection syndrome

dominant occipital lobe and splenium of corpus callosum; usually due to posterior artery stroke (right homonymous hemianopia with alexia [cannot read] but not agraphia [can write])

Cortical Lesions

Cause disorders of visual integration

Visual information from LGB goes to primary visual cortex (V1) of both occipital lobes; further processing occurs in areas V2–V5

To read, information travels from visual cortex to angular gyrus in parietal lobe of dominant hemisphere (usually on left side); visual information from right hemifield is transmitted directly from left occipital lobe to ipsilateral angular gyrus, and information from left hemifield is transmitted through splenium of corpus callosum to contralateral angular gyrus

Large left occipital lesions that also disrupt fibers crossing in splenium of corpus callosum from right occipital cortex to left angular gyrus; information from left VF cannot travel to left parietal lobe (angular gyrus); patient is blind in right visual field, can see and write but not read, even what they have just written

Disorders During Pregnancy

Occur more commonly with eclampsia and preeclampsia

Conditions

central serous retinopathy (CSR), hypertensive retinopathy, Purtscher’s-like retinopathy, RD, cerebral venous thrombosis, CRAO, carotid cavernous fistula, Sheehan’s syndrome (postpartum pituitary infarct causing panhypopituitarism; secondary hemorrhage can cause CN 2-6 palsies)

Venous abnormalities: during first 6 weeks postpartum (venous sinus thrombosis presents with headache and papilledema).

Brain Tumors

(Table 4-1)

Table 4-1 Classification of brain tumors

By origin:
Glial (gliomas)	Astrocytoma
Neuronal	Neuroblastoma, medulloblastoma
Connective tissue	Sarcoma
Lymphoreticular	Primary (non-Hodgkin’s) CNS lymphoma
Blood vessels	Hemangioma, angioma
Bone	Osteoma
Neural crest Congenital rests: Notochord Adipose cells Ectodermal derivatives Glands: Pituitary gland Pineal gland	Meningioma (arachnoid cells), primary CNS melanoma
	Chordoma
	Lipoma
	Craniopharyngioma, teratoma, dermoid
	Adenoma
	Pineocytoma, pineoblastoma, germ cell tumors
By age:
<20 years old	CNS tumors are second most common type of malignancy (leukemia is first); approximately 66% located in posterior fossa; gliomas of cerebellum, brain stem, optic nerve; pinealomas; primitive neuroectodermal tumors; craniopharyngiomas
20–60 years old	Meningiomas, gliomas of cerebral hemispheres, pituitary tumors
>60 years old	Malignant gliomas, metastases