Clinical Neuro-Ophthalmology

Surat Tanprawate, MD, MSc(London), FRCP(T)

Neurology Unit, Department of Medicine
Chiang Mai University

Slide download: FB: openneurons

 The scope of
Neuro-Ophthalmology

• Oculomotor system • Visual perception system

• conjugate eye movement • Eyelids

• Saccadic system • Pupils

• Pursuit system

• Vergence system

• Counter rolling system:

VOR, Ocular fixation
system
 Oculomotor
pathway
• Supranuclear(UMN)
• FEF: horizontal conjugate gaze
• Diffuse frontal and occipital:
vertical conjugate gaze
• Nuclear (LMN)
• Nerve III, IV, VI Nucleus
• Internuclear
• PPRF, abducen interneuron,
MLF (Horizontal gaze)
• riMLF, INC, PC (Vertical gaze)
• Infranuclear(LMN)
• Fasciculus
• Cranial nerve
• NMJ
• Muscle
Frontal eye fields
 Right frontal lobe infarct
Frontal lobe lesion: no diplopia
- Destructive to FEF lesion:
• eyes deviate to the lesion
- Destructive to Pontine lesion:
• eyes deviate contralateral to the lesion
- Excitatory lesion:
• eyes deviate contralateral to the lesion
Dysconjugate eyes
Diplopia (double vision)

• Diplopia is the simultaneous

perception of the two images
of a single object that may
be displaced horizontally,
vertically, diagonally

• caused by impair EOMs

functions
pic from wikipedia
 Diplopia
Monocular Binocular
diplopia diplopia

Repetitive Ghosting
images image Misalignment of
the eyes

- Cerebral polyopia - Retinal disease Nuclear Infranuclear Internuclear

- Non-organic - Refractive error control control control

- CN III - CN palsy Horizontal diplopia

- CN IV - NMJ disorder - INO
- CN VI - Muscle disorder - PPRF
Vertical diplopia
- INC, riMLF
 Infranuclear control

Muscle Fasciculus
Nerve

NMJ
Ophthalmotrope (Ruete, 1857)

bjo.bmj.com/content/93/5.cover-expansion
 Nuclear and Internuclear control

III
IV

VI

Nuclear control:
Nucleus III, IV, VI
Horizontal gaze Vertical gaze
internuclear control internuclear control
 Steps to exam patient with
diplopia
1. Monocular vs Binocular diplopia

2. Exam eye movement: primary position and EOM

3. Other finding

a.eye lids

b.pupils

c.other cranial nerve

4. Specific findings/tests: fatigue test, weakness distribution,

reflex, typical facial features, etc
 Key features
Nuclear and fascicular lesion

• Brain stem sign: long tract sign, other CN involvement

Nerve lesion

• Neighbourhood sign; other CN, other sign

Internuclear lesion

• Specific syndrome; Internuclear Ophthalmoplegia (INO),

WEBINO, One and a half syndrome

NMJ lesion

• Fatiguability, not consistent with CN lesion, sign of

myasthenia gravis

Muscle lesion

• Not consistent with CN lesion: not consistent with CN lesion,

sign of myopathy
Nuclear and nerve
lesion
 CN III

The oculomotor nerve (cranial nerve III)

 Feature of CN III palsy
• Clinical features: Ophthalmoplegia(MR, SR, IR, IO),
Ptosis, Pupillary dilatation

• Part

• nuclear complex->fasciculus->basilar-
>intracavernous->intraorbital

• pupillomotor fibres
Stroke syndrome of CN III
palsy

1. Weber’s syndrome

2. Benedikt’s syndrome

3. Nothnagel’s syndrome

4. Claude’s syndrome
 Weber’s
syndrome

• Contralateral
hemiparesis

• Ipsilateral CN III
palsy

• +/- contralateral
parkinsonism,
http://www.cram.com
corticobulbar palsy

• cause: stroke, mass

lesion
Benedikt’s syndrome
(paramedian midbrain
syndrome)

• Ipsilateral CN III
palsy

• Tremor (red nucleus)

http://www.cram.com

• Contralateral
extrapyramidal sign

Note: Nothnagel: ipsi CN III palsy+cerebellar ataxia

Claude: Benedikt + Nothnagel
 Isolated CN III palsy

Pupils sparing vs non-pupils sparing

Posterior communicating artery aneurysm
causing CN III palsy
 Isolated CN III palsy with
sparing pupil in ischemic nerve
 Direct light reflex

Upward

Neutral position
Right gaze Left gaze

Downward
Oculomotor nuclear
complex lesion
A woman with diplopia for 1 month
Tuberculoma at midbrain
 Key finding of nuclear
complex CN III lesion

• incomplete involve muscle innervated with CN III

• +/- ptosis

• +/- pupillary involvement

• +/- other brain stem sign

 CN IV

The course of the trochlear nerve in the pons

34
Head position in Forth nerve palsy

Head tilt chin down to unaffected side

 Parks three steps to identify
CN IV palsy
1.which eye is higher in primary gaze?

2.Worse in right/left gaze?

3.Which head tilt gives greater hyperdeviation?

• “Left-Right-Left” • “Right-Left-Right”

• Left SO palsy • Right SO palsy

“Left SO palsy”
 Cause of isolated CN IV in
adult
• 30% Unknown

• 20% Ischemic

• 10% Aneurysm

• 40% Traumatic

• CN IV is the longest and thinnest CN, and passes over the

tentorium cerebelli
 CN VI

facial nerve wraps around the nucleus of cranial nerve VI within

the pons
• Part: nuclear->fasciculus->basilar (subarachnoid
space-> base of skull, petrous bone)—
>intracavernous->intraorbital
Stroke syndrome related to
CN VI palsy

1. Foville syndrome

2. Millard-Gubler syndrome
 Millard-Gubler syndrome (ventral pontine syndrome)

1. CN: ipsilat CN VI + CN VII

2. Corticospinal tr (contralat
hemiparesis)

“Cross hemiplegia”
 Foville’s syndrome (inferior medial pontine syndrome)

1. CN VI, VII (ipsilat.)

2. Corticospinal tr. (hemiparesis)

3. Spinothalamic tr. (contralat.

hemisensory loss)

4. PPRF (lateral gaze weakness)

 Basilar portion of CN VI
palsy
1. Acoustic neuroma: hearing
loss+CN VI palsy (first sign is
diminished corneal sensitivity)
2. IICP
3. Nasopharyngeal tumours:
invade the skull
4. Basal skull fracture
5. Gradenigo syndrome: acute
petrositis (CN VI + CN VII
palsy + hearing loss + Pain)

Diagnos(c  criteria  of  Gradenigo  syndrome  

Suppurative otitis media  
Pain in the distribution of the trigeminal nerve  
Abducens nerve palsy
Bilateral LR could be pseudo sixth nerve
palsy from IICP
Isolated CN VI palsy
 Multiple nerve involvement

• Cavernous sinus syndrome

• Superior orbital fissure syndrome
 Cavernous sinus syndrome
• Association with
– other cranial nerve involvement:
4, 5, 6 CN
– oculosympathetic paralysis
– Opthalmic branch of trigeminal
nerve
• Tend to be partial; alls
muscles innervated are not
equally involved

29
Superior orbital fissure
syndrome

CN 3, 4, 6, V1
30
 Superior orbital fissure syndrome

• Involve CN 3, 4, 6 and V1 CN 5
distribution +/- oculosympathetic
paresis without anhydrosis
• May exopthalmos due to
blockade of the opthalmic veins
• Blindness due to extension of
the pathologic process to
involve the optic canal

31
Interneuclear
lesion
Horizontal
Interneuclear ophthalmoplegia (INO): MLF lesion
Bilateral INO : Bilateral MLF lesion
One and a half syndrome: PPRF lesion + MLF lesion
 Unilateral MLF lesion
• “ internuclear
ophthalmoplegia “
• Ipsilateral MR weakness ipsilateral side
• Contralat. abducting nystagmus
Interneuclear ophthalmoplegia (INO)

a. Normal primary b. Left impaired adduction

position       on right gaze and horizontal
nystagmus of the right eye

c. Normal left abduction on d. Normal convergence

left gaze
 Bilateral MLF lesion
• Bilateral MLF lesion
–Bilateral adducting weakness
–Bilateral abducting nystagmus
–Impaired vertical vestibular and pursuit
–Impaired vertical gaze holding
–Gaze evoked nystagmus
• Wall eyed bilateral INO : WEBINO
–exotropia
A man with sudden diplopia

WIBINO
 One and a half syndrome
• Combined lesion :
PPRF and MLF
• “ One and a half
syndrome “
– Ipsilateral horizontal gaze
palsy
– INO
Bilateral PPRF lesion

• Bilateral horizontal gaze failure

• Sparing vertical gaze
• Sparing pupil
• May combine with other brain stem sign
A woman with diplopia and facial palsy
Interneuclear lesion
Vertical
Upward and downward gaze failure
Vertical gaze control
 A middle age woman with acute dizziness
Firstly, she was diagnosed as exophthalmos
and tested for TFT (but normal)
 Dorsal midbrain syndrome
Parinaud’s syndrome
• A group of eye abnormalities and pupillary dysfunction caused
by lesions of the dorsal midbrain

• Clinical syndrome

• Upward gaze palsy (supranuclear)

• Pseudo-Argyll Robertson pupils: light-near dissociation

• Convergence-Retraction nystagmus/ convergence spasm

• Eyelid retraction (Collier’s sign)

• “Setting sun” sign (conjugate down gaze in primary position)

 cases
• compression

• ischemia/hemorrhage

• obstructive hydrocephalus

• infection

• tumour
 Syndrome of
ophthalmoparesis

• Miller-Fisher syndrome

• Wernicke encephalopathy
A patient with diplopia for 1 week with gait
ataxia and areflexia

2 weeks 2 months
Dx. Miller Fisher syndrome
in a patient with polyneuropathy, all CN can be involved
causing total ophthalmoplegia
Wernicke’s encephalopathy

• Triad

• ophthalmoparesis/nystagmus

• acute confusion

• ataxia
 A pancreatic cancer patient with NG tube feed
for 3 months
She develop confusion with ataxia and dizziness
Victor M, et al. The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to
Alcoholism and Malnutrition. 2nd ed. 1989.
 Treatment regime
• Thiamine IV is recommended

• No consensus the dose and duration

• IV route

• Although standard recommended dose interval is once

daily but half life is 96 mins so may need multiple time
daily

• Standard dose is 100 mg iv

• EFNS task force: 200 mg three times daily

R Galvin et al. European Journal of Neurology 2010, 17: 1408–1418
Infranuclear lesion ;

disease of NMJ
disease of ocular muscle
Neuromuscular Junction
 Features of NMJ
disorder
• Ophthalmoplegia is not consistent with
nerve distribution

• Fatigue
• Fluctuating course
• with other muscle weakness esp. ptosis,
proximal muscle weakness
A patient with diplopia and ptosis
Eyelid and ptosis
• Upper eyelid
–Levator palpebral
superioris(CN 3)
–Muller
muscle(sympathetic)
–Frontalis muscle(CN 7)
• Lower eyelid
–Capsulopalpebral
fascia(inferior rectus)
–Inferior tarsal
muscle(sympathetic)
 Ptosis
Non-neurogenic(mechanical)
ptosis

Neurologic ptosis

Congenital ptosis

•Uni-bilateral •Pupil involvement

•Partial-complete •EOM impairment

Supranuclear LMN Horner’s

•Neuropathic(N,
lesion(cerebral syndrome
fascicle, CN)
ptosis) •NMJ
•Contralateral •Myopathic
cerebral hemisphere
Ptosis from Cranial nerve III lesion

- complete or near complete ptosis

- EOM involvement

- Pupil dilatation
 MG with enhancing ptosis

Ptosis due to NMJ lesion: sign of fatiguability

 Horner’s syndrome

• miosis

• ptosis (incomplete, upside down)

• anophthalmos

• anhidrosis
Afferent visual pathway
and visual loss
Visual loss
• Assessment

• Visual acuity

• Pupillary reflex

• Visual field

• Fundus
 Visual loss
Non-neurological
Diplopia causes
-refractive error
Neurologic causes -corneal problem
-cataract
-glaucoma
-retinal and choroidal
disease

Type of visual field

defect

Anterior visual pathway Posterior visual pathway

-Prechiasmatic lesion -LGB
-Chiasmatic lesion -Geniculo-occipital lobe
pathway
-Retrochiasmatic lesion -Occipital lobe
 Assessment causes of visual loss
• Unilateral or bilateral
• Transient, non-
progressive, progressive
• Sudden, gradual onset

• Sudden onset • Gradual onset

• Transient: monocular, binocular
• Non-progressive: monocular,
binocular
• Progressive : monocular, binocular
 1) Visual loss of sudden onset
Unilateral transient visual loss • Disc:
• Ocular: – trainsient visual
• angle closure glaucoma, obscuration(chronic swelling
hyphema, optic disc edema, of optic disc)
partial retinal v. occlusion • Optic nerve:
• Retinal artery: – Uhthoff’s phenomenon in ON
• vasospasm(migraine),
• hypoperfusion(hypotension,
hyperviscosity,
hypercoagulable stage),
• vasculitis(GCA),
• TIA(TMB, amaurosis fugax;
emboli to retinal circulation)
 Visual loss of sudden onset
Bilateral transient visual loss
• Disc:
– papilledema(transient visual obscuration)
• Transient visual cortex dysfunction:
– Decrease perfusion: thromboembolism, systemic
hypotension, hyperviscosity, vascular
compression
– Epilepsy
– Migraine
 Visual loss of sudden onset
Non-progressive unilateral sudden visual loss
• Hallmark of ischemic of optic nerve or retina
• CRAO, CRVO, AION
• Central serous choroidopathy
• Retinal detachment
• Vitreous hemorrhage
• Functional visual loss
 Visual loss of sudden onset
Non-progressive bilateral sudden visual loss
• Occipital lobe infarct
• Pituitary apoplexy
• Functional visual loss
• Head trauma
 Visual onset of visual loss
Sudden onset with progressive visual loss
• Hallmark of inflammatory lesion: optic neuropathy
• Ocular: low-tension glaucoma
• Disc: papilledema
• Anterior visual pathway:
– Inflammation: optic neuritis,
– Hereditary: LHON
– Toxic neutritional optic neuropathy
– Compression: aneurysm, tumor, dysthyroid optic neuropathy
– Radiation
– Paraneoplastic retinopathy/optic neuropathy
 Relative afferent pupillary defect (RAPD)
(Marcus Gunn pupil) with swing flash light test
 2) Visual loss of gradual onset
• Hallmark of compressive lesion
• Affect: prechiasmal, chiasmatic visual pathway
• Common: pituitary tumor, aneurysm, craniopharyngioma,
meningioma, glioma
• Granulomatous involvement: TB, sarcoidosis
• Ocular dysthyroidism
• Hereditary or degenerative of retina or optic nerve
• Normal tension glaucoma
• Chronic papilledema from pseudotumor cerebri
• Medication: toxic to optic nerve
• Radiation damage to anterior visual pathway
• Rapid pregressive paraneoplastic retinopathy/optic neuropathy
Pupillary and eyelid
abnormality
 Pupillary abnormality
• Evaluation of pupillary abnormality
• Size and shape of pupil
• Reaction of pupil
– Light reaction
• Direct light reflex
• Indirect(consensual) light reflex:
swing flash light test
• Near(Accommodation) reflex:
106
 Abnormal pupil
• Size abnormality • Abnormal pupillary
• Unequal size(anisocoria) reflex
• Abnormal equal size: – Abnormal light reflex
miosis VS mydriasis Abnormal direct light reflex
Abnormal consensual light
• Shape abnormality reflex: RAPD
• Pupillary irregularity – Abnormal near reflex
– Light- near dissociation
 Anisocoria
Opthalmologic Simple(physiologic
anisocoria ) anisocoria
Neurologic anisocoria

Symp: ptosis,
anhydrosis Visual
Parasymp: ptosis. system
EOM

Pupil dilatation pathway Pupil constriction

abnormality pathway abnormality
(anisocoria greater in -Adie’s pupil
darkness) -CN3 palsy
-Horner’s syndrome
-old Adie’s(Tonic) pupil
-Aberrent degeneration
 Poorly reactive pupil without
anosocoria
• Large pupil
– Hypothalmic lesion, midbrain lesion, syphilis,
botulism, MFS, autonomic neuropathy, drug/toxic,
anxiety
• Small pupil
– Old age, syphilis, diabetes, long standing Holme
Adie’s pupil, congenital, drug/toxic
 Common pupil syndrome
• Adie Tonic pupil
• Adie’s syndrome
• Light near dissociation
• Argyll-Robertson pupil
• Parinaud’s syndrome
• Horner’s syndrome
 Tonic (Holme-Adie)pupil
• Typically: unilateral mydriasis in healthy
young women
• Acute: large
• Months to years: small
• React to light: sluggish or slow reaction to
light and slow(tonic) near response
• Cause: postganglionic parasympathetic
denervation
 Light near dissociation
• Absent or impair light reflex with preserved
accommodation reflex and convergence
• Cause:
– DM: small vv disease
– Dorsal midbrain syndrome
– Argyll-Robertson pupil
– Adie pupil
– Afferent visual pathway lesion
 Argyll-Robertson pupil
• Small, irregular, unequal
• Normal afferent visual system
• Light near dissociation
• Cause: neurosyphilis
 Relative afferent pupillary defect

Marcus Gunn pupil
• Swing flashlight test
• Cause
• Asymmetrical optic nerve disease
• Extensive retinal damage
 Pupillary irregularity
• Most: local disease of iris
• Syphilis
• Ischemia
• Posterior synechiae
• Traumatic iridoplegia
• Degenerative disease of iris
• Holmes Adie syndrome
Localization of Horner’s
syndrome
Nystagmus
 Nystagmus
• Ancient Greek (nustagmos (Ancient
Greek, "nodding, be sleepy")

• Involuntary biphasic rhythmic ocular oscillation in

which one or both phase are slow

• The slow phase is responsible for the initiation

and generation of the nystagmus, whereas the
fast (saccadic) phase i a corrective movement
bringing the fovea back on target

• Type: jerk (direction to fast phase) ; pendular

nystagmus
 Mechanism

• Nystagmus may result from dysfunction

of the vestibular ending organ,
vestibular nerve, brainstem, cerebellum,
or cerebral centre for ocular pursuit
 Peripheral vs Central nystagmus
Peripheral nystagmus
• Severe vertigo
• Minute to Day to weeks duration
• Hearing loss, tinnitus associated
• Usually horizontal with torsion
• Very rarely purely vertical or
torsional
• Commonly peripheral vestibular
organ dysfunction: labyrynthitis,
meniere’s disease
Central nystagmus
• None or mild vertigo
• Often chronic
• May be purely vertical or
torsional
• Visual fixation usually has no
effect
• Downbeat, upbeat, torsional
• Etiologies commonly vascular,
demyelination, pharmacologic,
toxic
 A schematic illustration of nystagmus waveforms

(A) pendular nystagmus

(B) an accelerating velocity

exponential slow phase jerk
nystagmus (CN)

(C) a decelerating exponential

slow phase jerk nystagmus
(MLN)

(D) a linear or constant velocity

slow phase jerk nystagmus
(MLN)

In (A) a slow phase is followed by a slow phase while in (B)–(D)

a slow phase is followed by a fast phase
 Mechanism
• Pendular nystagmus: is central (brainstem/
cerebellum)

• Jerk nystagmus:

• linear (constant velocity) slow phase: peripheral

vestibular dysfunction

• slow phase has decreasing velocity exponential:

brainstem neural integrator, cerebellar

• slow phase has increasing velocity exponential:

central in origin (usual form of congenital
nystagmus)
The Neurologist
CMU
The Neurologist
CMU