Clinical Neuro-Ophthalmology
Surat Tanprawate, MD, MSc(London), FRCP(T)
Neurology Unit, Department of Medicine
Chiang Mai University
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)
pic from wikipedia
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
Diplopia
Monocular
diplopia
Repetitive
images
- Cerebral polyopia
- Non-organic
Binocular
diplopia
Ghosting
image
- Retinal disease
- Refractive error
Misalignment of
the eyes
Nuclear
control
- CN III
- CN IV
- CN VI
Infranuclear
control
- CN palsy
- NMJ disorder
- Muscle disorder
Internuclear
control
Horizontal diplopia
- INO
- PPRF
Vertical diplopia
- INC, riMLF
Infranuclear control
Muscle
Fasciculus
Nerve
NMJ
IO
SR
LR
MR
SO
IO/SR
IR
SR/IO
SO/IR
IR/SO
MR
MR
SR
IO
MR
LR
IR
SO
CONVERGENCE
emedicine.medscape.com/article/
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
internuclear control
Vertical gaze
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
The action and nerve supply of the extraocular
muscles is demonstrated
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. Webers syndrome
2. Benedikts syndrome
3. Nothnagels syndrome
4. Claudes syndrome
Webers
syndrome
Contralateral
hemiparesis
Ipsilateral CN III
palsy
+/- contralateral
parkinsonism,
corticobulbar palsy
cause: stroke, mass
lesion
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Benedikts syndrome
(paramedian midbrain
syndrome)
Ipsilateral CN III
palsy
Tremor (red nucleus)
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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
Oculomotor nuclear
complex lesion
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
SO function
Depression
Intorsion
Abduction
SR
IO
IR
SO
Head position in Forth nerve palsy
Head tilt chin down to unaffected side
Forth nerve palsy: which side is affected
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
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
(subarachnoidbase od 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
Fovilles 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)
Diagnostic 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
position
c. Normal left abduction on
left gaze
b. Left impaired adduction
on right gaze and horizontal
nystagmus of the right eye
d. Normal convergence
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
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
Interneuclear lesion
Vertical
Upward and downward gaze failure
Vertical gaze control
Dorsal midbrain syndrome
Parinauds 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 (Colliers 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
Wernickes encephalopathy
Triad
ophthalmoparesis/nystagmus
acute confusion
ataxia
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: 14081418
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
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
Partial-complete
Supranuclear
lesion(cerebral
ptosis)
Contralateral
cerebral hemisphere
Pupil involvement
EOM impairment
LMN
Neuropathic(N,
fascicle, CN)
NMJ
Myopathic
Horners
syndrome
Ptosis from Cranial nerve III lesion
- complete or near complete ptosis
- EOM involvement
- Pupil dilatation
Horners 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
causes
-refractive error
-corneal problem
-cataract
-glaucoma
-retinal and choroidal
disease
Diplopia
Neurologic causes
Type of visual field
defect
Anterior visual pathway
-Prechiasmatic lesion
-Chiasmatic lesion
-Retrochiasmatic lesion
Posterior visual pathway
-LGB
-Geniculo-occipital lobe
pathway
-Occipital lobe
Assessment causes of visual loss
Unilateral or bilateral
Transient, nonprogressive, progressive
Sudden, gradual onset
Sudden onset
Transient: monocular, binocular
Non-progressive: monocular,
binocular
Progressive : monocular, binocular
Gradual onset
1) Visual loss of sudden onset
Unilateral transient visual loss
Ocular:
angle closure glaucoma,
hyphema, optic disc edema,
partial retinal v. occlusion
Retinal artery:
vasospasm(migraine),
hypoperfusion(hypotension,
hyperviscosity,
hypercoagulable stage),
vasculitis(GCA),
TIA(TMB, amaurosis fugax;
emboli to retinal circulation)
Disc:
trainsient visual
obscuration(chronic swelling
of optic disc)
Optic nerve:
Uhthoffs phenomenon in ON
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
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:
92
Abnormal pupil
Size abnormality
Abnormal pupillary
reflex
Unequal size(anisocoria)
Abnormal equal size:
miosis VS mydriasis
Shape abnormality
Pupillary irregularity
Abnormal light reflex
Abnormal direct light reflex
Abnormal consensual light
reflex: RAPD
Abnormal near reflex
Light- near dissociation
Anisocoria
Opthalmologic
anisocoria
Simple(physiologic
) anisocoria
Neurologic anisocoria
Symp: ptosis,
anhydrosis
Parasymp: ptosis.
EOM
Pupil dilatation pathway
abnormality
(anisocoria greater in
darkness)
-Horners syndrome
-old Adies(Tonic) pupil
-Aberrent degeneration
Visual
system
Pupil constriction
pathway abnormality
-Adies pupil
-CN3 palsy
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
Adies pupil, congenital, drug/toxic
Common pupil syndrome
Adie Tonic pupil
Adies syndrome
Light near dissociation
Argyll-Robertson pupil
Parinauds syndrome
Horners 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 Horners
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
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
Severe vertigo
Minute to Day to weeks duration
Hearing loss, tinnitus associated
Usually horizontal with torsion
Very rarely purely vertical or
torsional
Central nystagmus
Commonly peripheral vestibular
organ dysfunction: labyrynthitis,
menieres disease
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
Cocaine prevents the reuptake of norepinephrine at the motor endplate
and thus prolongs its action on the effector cell.
Differentiation between physiological anisocoria and
Horner's syndrome
