Transcript Pupillary deception

Pupillary deception
Sarah Dougherty Wood, OD,
MS, FAAO
Heart of America
February 2011
Presentation at the Boston VAMC
79 year old caucasian male
 CC: left eye lid closed x 2 weeks, when
the lid is lifted he sees double vision,
sudden onset
 No complaint of blurred vision
 No h/o ocular trauma or associated pain
 Ocular history: pc iol os (4 years prior),
mild dry amd ou, cataract od
 No ocular meds
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DDX
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Thyroid orbitopathy
Trauma
Myasthenia Gravis
Restriction of EOM due to a intraorbital mass
Horner’s syndrome
CPEO
Dorsal Midbrain syndrome
CN 3 palsy
Multiple cranial nerve palsies
Medical history
Systemic conditions: DM, atrial fibrillation,
high cholesterol, allergic rhinitis,
cardiomyopathy, asthma, HOH, HTN
 Systemic medications: coumadin,
simvastatin, furosemide, isosorbide,
lisinopril, loratadine, metformin,
metoprolol
 Last hba1c 6.7 (6-08)
 History of moderately heavy
EtOh use
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Examination findings
VA cc: od 20/25, os 20/25
 Complete ptosis os
 CT: left hypotropia (9prism diopters)
 Eoms: left eye superior restriction
 Diplopia reported in primary gaze but was
worst when attempting superior/abduction
and on left head tilt
 Confrontations full od, os (lid lifted)
 IOP TA: 16/15
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Other testing
CN 4,5,6,7,11 were all wnl
 Also important to note: pt had good
articulation of words and reported no
trouble with swallowing
 Pupils: reactive ou, no anisocoria, no apd
ou
 No other neuro signs found
 No new findings on slit lamp examination
or fundus examination
 No diabetic retinopathy
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At this point,
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This condition seems to be affecting……
Levator or Muller muscle? Which one will cause a
complete ptosis when denervated?
Levator
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Which EOMS? Which cause elevation?
Superior rectus and inferior oblique
Between these two, which one would be affected
if the diplopia gets worse the AB-duction?
Superior rectus
So,
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We suspected the superior rectus and
levator were involved…….
Let’s go back to our DDX list
Thyroid orbitopathy- certainly can cause
restriction and diplopia, but doesn’t cause
complete ptosis- actually lid retraction
 Trauma- could be inferior floor entrapment
but no h/o trauma per pt, cataract surgery
can sometimes cause a mild ptosis due to
levator dehiscence
 MG-would be unusual to affect only the
superior rectus and levator muscles on
one side, possible
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Differentials…………
Intraorbital mass- possible
 Horner’s syndrome- can cause a ptosis
due to affect on Muller’s muscle but would
likely not be so dramatic, can have
Horner’s with CN palsies (esp. CN6) if
there is a cavernous sinus lesion, no
miotic pupil
 CPEO- usually slowly progressive and
bilateral and external ophthalmoplegia in
all directions of gaze
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Dorsal midbrain syndrome-signs:
supranuclear paresis of upgaze, light-near
dissociation, pt had normal pupillary light
reflex
 Multiple CN palsies- no other neuro
abnormalities found
 CN3 palsy- If complete, eye would be
down and out with a ptosis- Is this our
patient?
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Review of CN3 pathway
CN3 Nucleus is located in the midbrain
 Runs through the red nucleus
 Exits ventrally
 Passes parallel to the posterior
communicating artery
 Runs through the cavernous sinus laterally
 Then divides into two divisions
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Two divisions of CN3
Splits within the cavernous sinus and
superior orbital fissure
 Inferior division: carries fibers which
innervate the MR, IO, and IR
 Superior division: carries fibers which
innervate the SR and levator palpebrae
 Therefore, we deduced we had a superior
division (incomplete) CN3 palsy
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What is your biggest concern with a
CN3 palsy?
Aneurysm!
 Which is the most common artery to have
an aneurysm which would involve CN3?
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Why is an aneurysm bad?
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Posterior communicating artery or the junction
of the PCA and ICA
Rupture, increased morbidity and mortality
Timely diagnosis is critical: From time of
CN3 palsy (due to aneurysm) to rupture of
PCA= avg. 29 days
Lee, et al
What exam findings could give us
information about the presence of an
aneurysm?
 Why will an aneurysm potentially affect
the pupil?
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Pupillary fibers are located superficially
(dorsal/medial location)
What will the pupil look like if it is in fact
involved?
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Fixed and dilated
Our patient
Pupils: reactive ou, no anisocoria, no apd
ou
 So, can we rule-out an aneurysm? Why or
why not?
 I intentionally left out a critical piece of
information about the inferior division of
CN3: it also carries the pupillary fibers to
the sphincter muscle
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So, no pupil involvement in an incomplete CN 3
palsy (superior division) gives you a false sense
of security
“Partial external dysfunction (EOM involvement
and/or lid) without pupil involvement is not the
same thing as true sparing with complete
external dysfunction”, Lee et al
YOU COULD STILL HAVE A LIFE-THREATENING
ANEURYSM IN YOUR CHAIR!
Send for a stat MRI/MRA
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Review of Acquired Complete CN3 palsy managementmost commonly ischemic but how do you know?
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Steps:
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1) Is it truly isolated? (HA, hemiparesis, other
CN palsies, eye pain?)
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2) Pupil involvement? (normal pupil function
defined as anisocoria less than or equal to
1mm and light reaction bilaterally, Lee et al)
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If not, send out ASAP for imaging
If yes, send out ASAP for imaging
3) Aberrant regeneration? (example: lid
retraction on down gaze, miosis during ADduction or downgaze)
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If yes, likely a compressive lesion, send for imaging
Review of CN3 palsy management in
general
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Steps continued:
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4) Less than 40 years of age?
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5) HTN, DM or vascular disease?
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If yes, send ASAP for imaging
If no, send ASAP for imaging
6) Resolution in 3 months? (100% of ischemic
isolated CN3 palsies resolved by 3 months,
Capo et al)
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If no, send for imaging
Summary of CN3 management
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Do not have to send for further testing if:
All EOMS are involved (SR, IR, IO, MR)
 +ptosis
 Pupil spared
 >40 y.o.a.
 Isolated AND
 Have systemic vascular disease (DM, HTN,
atherosclerosis)
These cases likely have a microvascular causeFollow closely for the 1st few days…..
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If pupil becomes involved, send
them for a STAT MRI/MRA or CT
angiography
If not, follow at 6 weeks
and then 3 months
Potential causes of superior division
CN3 palsies from the literature
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Microvascular
Post viral
Aneurysm (posterior cerebral, basilar apex,
superior cerebellar arteries)
Cavernous sinus or intraorbital mass
Midbrain infarction
Meningitis
Sphenoid sinusitis
Trauma
MG
Giant cell arteritis
How did we manage this patient?
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We sent for a STAT sed rate and CRP, MRI/MRA
and then to neuro-ophthalmology
Sed rate was 22 and CRP was 2.77
MRI/MRA result: paranasal sinusitis but no mass
or aneurysm or infarction
Our diagnosis: microvascular but MG is still a
possibility
Neuro-ophthalmology agreed with our diagnosis
of microvascular- dismissed pt back to optometry
I informed PCP about paranasal sinusitis
Patient returned to optometry 3 weeks
later (now roughly 6 weeks in duration)
and ptosis was the same but diplopia was
only present on attempted upgaze
 RTC 6 weeks (now roughly 3 months in
duration)- would we expect a
microvascular palsy to be resolved by this
point?
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Follow-up
Findings: 18 prism diopter left hypotropia
in primary gaze!, ptosis still the same
 Should we change our diagnosis?
 We sent him back to neuro-ophthalmology
who ran a CT scan of the orbit to r/o
orbital mass
 CT scan: no mass found
 Ran lab to detect Ach receptor antibodies- what are they looking for?
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Let’s review normal neuromuscular
transmission
Acetylcholine, a neurotransmitter, is
stored in the presynaptic vesicles in nerve
endings. An action potential causes
calcium to enter the cell and the vesicles
move to the surface and release the Ach.
 The Ach travels across the synaptic cleft
and attaches to a receptor on the postsynaptic muscle cell
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Normal NMJ
This causes increased permeability of Na+
and K+ and depolarization, if the
threshold is met, the action potential
propagates down the cell.
 This will lead to muscle contraction
 Acetylcholinesterase removes the Ach
from the receptor
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Myasthenia Gravis
A chronic auto-immune neuromuscular
disease
 Antibodies block, alter, or destroy the
receptors for acetylcholine at the
neuromuscular junction which prevents
the muscle contraction from occurring
 Causes weakness and fatigability of the
skeletal muscles of the body
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jama.ama-assn.org/.../small/jrc50002f1.gif
www.mda.org/publications/images/mg_NMJ.jpg
Myasthenia Gravis
Occurs in all ethnic groups. It most
commonly affects young adult women
(under 40) and older men (over 60), but it
can occur at any age.
 Prevalence: 4-5/100,000
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Ocular Myasthenia
90% of MG patients will have ocular signs,
in 60% it is the initial sign but rare to
have only eye signs during the entire
course of the disease
 Involvement of levator, orbicularis oculi,
one or all of the EOMS
 Signs: ptosis, diplopia
 usually variable- worse at the end of the
day or with fatigue
 Normal pupils
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Ocular Myasthenia- Tests you can do
Have the patient to look straight up for a
minute. Measure the palpebral fissure
before and after. MG=decreased PF
 Cogan’s lid twitch- Have patient look down
for 10-20 seconds and then have them
look back to primary gaze. The upper lid,
on the ptotic side, will raise and then
slowly begin to droop or twitch as it
settles back down
Miller, et al
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Ice Test- The strength of muscles improve
when they are cooled. Therefore, the
ptosis can be reduced in a rapid, safe,
inexpensive test. Measure the palpebral
fissure before and after putting ice on the
ptotic lid for 2 minutes.
 95% sensitive and 100% specific for MG
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Miller, et al
Our patient
Lab results: high levels of Ach receptor
antibodies (1.77, where normal is <0.3),
TSH normal- why is this relevant?
 Their cover test was 2 prism diopter left
hypotropia
 They sent him to neurology for another
test for MG- what is it?
 Tensilon test- how
does this work?
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Tensilon (Edrophonium) inhibits AchE
which potentiates the action of Ach and
will cause the ptosis to improve quickly
if the patient has MG
2-12-09 appointment
Neuro ran repetitive nerve conduction
studies. The right axillary nerve should
decreased amplitude of response after
exercise- which is consistent with a
neuromuscular transmission disorder
 Started him on Mestinon (pyridostigmine)
PO 30mg bid- what does this do?
 Pyridostigmine also is an antiacetylcholinesterase drug, it allows Ach to
remain longer on the nerve receptor
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2-26-09 f/u appointment
Pt noted ptosis os got better after first
dose of Mestinon but did not last
 Neurologist observed a ptosis now od and
restricted AB-duction OU
 Increased Mestinon to 60mg bid
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3-13-09 f/u with neuro-ophtho
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CC: lid droop is better- worse towards the end of
the day, does still have some diplopia- worse on
upgaze
Pupils, CT, and EOMS all wnl
Lid findings:
Marginal reflex distance-1
OD
4
OS
0 to -5
(distance from upper lid margin to pupillary reflex)
Palpebral fissure
13
(distance between upper and lower eyelids)
7
Assessment: MG with h/o incomplete CN 3
palsy, may have an element of levator
dehiscence from cat ext.
 What other systemic test should be run?
 Chest CT to r/o thymoma (anterior
mediastinum)
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Thymoma- tumor of the thymus glandabout 10% of those with MG have a
thymoma- need to test for it- the thymus
gland is involved in development our of
immune system= the connection to MG is
not completely understood
Patient had chest CT on 4-2-09
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Results: No thymoma
Other possible systemic involvement in
MG
Generalized skeletal muscle weakness
 Difficulty with the muscles used in
articulation, swallowing*, chewing,
breathing*, expression, and phonation
 Head ptosis due to weakness of neck
extensors
 Auto-immune disorders such as thyroid
 Overall, MG has a good prognosis- easily
managed with medications
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*potentially the most serious
Take Home message from this patient
Pupil findings are not helpful in an
incomplete CN 3 palsy!
 Also, if your initial diagnosis no longer
makes sense, do more investigating!
 Consider MG as possible diagnosis for any
diplopia patient
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Second patient, 3-26-09
Had known MG for 20 years and was being
treated, also had DM
 Came in complaining of worsening of
ptosis OS x 2-3 weeks
 Upon examination, the ptosis was worse
than previous exams and there was a left
hypotropia, no horizontal component
 Pupils normal
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Could this be a superior division CN3 palsy
on top of MG (Perhaps a diabetic CN3
palsy) or is it just the MG?
 The clinician did a very savvy thing- the
ice test and the ptosis completely resolved
 One more piece of the patient history: he
had recently been taken off one of his MG
medications
 A CT scan was run and was wnl
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f/u with neurology
Ach antibody test was wnl
 They believe it is an ischemic CN 3 palsy
 Kept the MG medications at the same level
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References
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Bhatti, et al, Superior Divisional Third Cranial Nerve Paresis, Arch
Neurol/Vol. 63, May 2006, p. 771-776.
Blake, et al, MR of Oculomotor Nerve Palsy, AJNR Am J Neuroradiol
16:1665-1672, September 1995.
Capo, et al, Evolution of oculomotor nerve palsies. J Clin Neuroophthalmol
12:21-5,1992.
Celebisoy, et al, Superior Division Paresis of the Oculomotor Nerve: Report
of Four Cases, Eur Neurol 2006;56:50-53.
Friedman, Pineda, Kaiser, The Massachusetts Eye and Ear Infirmary
Illustrated Manual of Ophthalmology, 1998, W.B.Saunders Company.
Lee, et al, The Evaluation of Isolated Third Nerve Palsy Revisited: An
Update on the Evolving Role of Magnetic Resonance, Computed
Tomography, and Catheter Angiography, Survey of Ophthalmology, Vol.
47, Number 2, March-April 2002, P. 137-157.
Miller, Newman, Biousse, Kerrison, Walsh and Hoyt’s Clinical Neuroopthalmology: The Essentials, Second edition, Lippincott, Williams, and
Wilkins, 2008
http://www.ninds.nih.gov/disorders/myasthenia_gravis