By David Katz, MD

1. David M Katz, MD
Bethesda Neurology, LLC
7830 Old Georgetown Rd, C-20
Bethesda, MD 20814
301.540.2700

2. Patient #1
 73-year-old healthy female seen 2/20/13
complaining of sinus pressure around her eyes
and blurred vision OD for several weeks
 Internist prescribed two rounds of antibiotics for a presumed
sinus infection
 Vision blurred OD 3 weeks ago
 Transient blurred vision OS 10 days ago
 CT orbits ordered by PMD normal

3. Patient #1
 Sees optometrist and ophthalmologist:
 Vacc 20/400 OD, 20/20 OS
 No relative afferent pupillary defect (APD)
 Confrontation visual fields full OU
 Funduscopic exam: normal, no optic disc edema or
atrophy

4. Patient #1
 Differential Diagnosis?
 Infection? (no pain, proptosis, injection, normal CT sinuses)
 Bilateral retrobulbar optic neuritis? (too old)
 Anterior ischemic optic neuropathy/AION? (no disc swelling or heme)
 Functional visual loss? (no secondary gain)
 Chiasmal lesion? (no bitemporalhemianopsia)
 Retrogeniculate lesion? (no homonymous hemianopsia)
 Toxic optic neuropathy? (not symmetrical, no atrophy)
 Leber’s Hereditary Optic Neuropathy? (too old, wrong sex, normal appearing
nerves)
 Posterior ischemic optic neuropathy/PION? (no blood loss, no recent surgery
or severe trauma)
 Why no RAPD? Because both optic nerves must be affected or it’s retinal or
functional
 Work up? (hint, a $10 test)

5. Patient #1
 ESR=95 (nl<40 for age)
 CRP=108 (nl<8)
 Diagnosis: Giant Cell Arteritis
 Work up: unilateral 2.5 cm temporal artery biopsy
positive (done 2/22/13)
 Treatment: IV methylprednisolone (Solumedrol) 1 g/d
x 5 days, then oral prednisone 100 mg/d
 Bi-weekly ESR/CRP and taper prednisone according
the lab results and residual symptoms

6. Temporal Artery Biopsy: H&E stain

7. Temporal artery biopsy
 Thickening of the intima, necrosis of the internal
elastic lamina and media and lymphocytic
infiltration of the vessel wall with giant cells are
seen acutely. Biopsies of patients on steroids >2
weeks show disruption of the internal elastic
lamina but few or no lymphocytes or giant
cells, termed “healed arteritis”.
 A temporal artery biopsy specimen > 2 cm
confirms the diagnosis in 95% of cases. If
negative, a contralateral biopsy has a yield of only
3% (Boyev 1999).

8. Arteriticischemic optic neuropathy
 Vision loss from GCA is most often due to
ischemic optic neuropathy (ION), either
A(nterior)ION (with disc swelling and
heme) or P(osterior)ION (without) as in
this patient
 GCA can also cause CRAO or
choroidalinfarctions
 GCA patients tend to be older (mean age=75
years) than non-arteritic ION patients
(mean age=57 years)

9. GCA diagnosis
 Symptoms: headache, scalp tenderness, jaw
claudication, swollen and pulseless
superficial temporal
arteries, PMR, fatigue, weight
loss, fever, malaise, transient monocular
blindness, diplopia
 Elevated ESR present in >90% of patients

10. GCA treatment
 High dose steroids must be initiated as soon as the
diagnosis is considered, don’t wait for TABx results
 Return of vision after steroid initiation is <15%
 There is anecdotal evidence that high dose IV steroids
(methylprednisolone IV 1 g x 5 days) may be more effective
than high dose oral steroids (ex. 100mg prednisone) at
preventing further vision loss . Patients with recent and/or
bilateral visual loss are better candidates for IV steroids
until a well designed study proves otherwise
 Delayed diagnosis of GCA is the #1 cause of medical
malpractice in ophthalmology (and I assume optometry)

11. Arteritic AION NA-AION

12. NA-AIONArteritic ION
 Mean age=57  Mean age=75
 Va>20/60 in 50%  Va<20/200 in 70%
 Hyperemic disc swelling  Pallid disc swelling
 Small or absent cup  Cups of any size
 Second eye involvement in 15%
at 5 years  Second eye involvement in 50%:
1/3 within 1 day, 1/3 within 1
week and1/3 within 1 month
 Cup enlarges once edema
 Cup unchanged once edema
resolves resolves
 FA shows late disc leakage  FA shows late disc leakage and
 Cotton wool spots and retinal patch choroidal non-perfusion
infarcts are very rare  CWS very common

13. Patient #2
 65 yo hypertensive female presents
with painless, progressive unilateral
ptosis and binocular diplopia and
generalized headache for two weeks

14. What’s the problem and what’s the cause?

16. Diagnosis?
 Pupil involved, partial right III nerve palsy
 Cause?
 Microvascular “diabetic” III (not a complete, pupil
sparing III n palsy)
 Midbrain stroke (no hemiparesis or ataxia, III nerve
progressive, not acute in onset)
 Myasthenia gravis (pupil involved)
 Restrictive (no proptosis, pain or eyelid retraction)
 Compressive lesion (tumor or aneurysm) must be
excluded immediately

17. A right third nerve
palsy caused by a
ruptured right posterior
communicating artery
(Pcom) aneurysm. The
CT shows subarachnoid
blood in the
quadrigeminal cistern
and the arteriogram
shows a Pcom
aneurysm
Endovascular coiling
successful
III nerve palsy resolved
over several months

18. III nerve palsy evaluation
 Pupil-involved III nerve palsy or progressive III nerve palsy: requires
immediate attention. Start with an MRI + gad and MRA brain. If normal
and suspicion is still high, proceed with CT angiogram (CTA). Use LP if
imaging studies are non-diagnostic and suspicion still high for SAH.
Cerebral arteriogram with endovascular coiling treatment of choice for
aneurysms with small necks
 Acute partial III nerve palsy without headache: start with MRI and MRA.
If pupil spared, check pupils daily and if remains normal, CTA or LP not
needed. If pupil dilates, proceed with CTA or arteriogram
 Pupil-sparing complete III nerve palsy: if isolated in a >40-year-old
check for diabetes and HTN. Do not need to proceed with emergency
imaging. If doesn’t improve by 2 months, proceed with MRI and MRA. If
>60, especially with new onset headache, check ESR and CRP for giant
cell arteritis
 Aberrant regeneration of III nerve: eyelid retraction in adduction
and/or infraduction, miosis in adduction. Only caused by compression
(aneurysm, tumor, prior trauma) and requires imaging study if no
trauma history

19. Case #3
 22-year-old previously healthy female was
admitted to her local hospital in Portsmouth,
VA with progressively worsening confusion,
lethargy, gait instability which, according to
her family began several weeks prior (patient
unable to give history)
 An inpatient ophthalmology consult was
requested to evaluate abnormal eye movements
noted by the family, ICU staff and neurology
consultant

20. History of Present Illness
 Two weeks prior to admission, patient presented to her local
ER with weakness, fatigue, blurred vision, gait
instability, memory loss and dizziness.
 59 lb weight loss since bariatric surgery three months prior
 BP 100/70, P=114
 Diagnosis: “non-specific vertigo”. Discharged on meclizine

21. Medical History
 Past medical history
 Morbid obesity, BMI=44 (obese>30)
 Obstructive sleep apnea, not using CPAP
 Hypercholesterolemia
 Past surgical history
 Laproscopic Roux-en-Y gastric bypass three months prior
 Past ocular history
 Strabismus surgery age 5 for congenital exotropia. Baseline visual acuity (VA)
20/20 OD, 20/50 OS
 Medications
 Multi-vitamin, iron, oral B12
 Allergies
 None known
 Family history
 Diabetes, obesity, glaucoma, coronary artery disease
 Social history
 Denied alcohol, tobacco, illicit drugs. Full-time college student

22. Neuro-Ophthalmological Exam on
Admission
 Visual acuity uncorrected: 20/100 OU at near
 Confrontation visual fields: full OU
 Ocular motility:
 Intermittent upbeat nystagmus in primary position OU
 Impaired supraduction OU
 Normal convergence
 Alternating exotropia
 Pupils: No RAPD, 2.5 mm in darkess, 1+ reactive to light
and near OU
 Intraocular pressure: 15 OD, 17 OD via Tonopen
 Biomicroscopic exam: unremarkable
 Fundus: unremarkable optic discs, vessels and retinae

23. Neurologic Exam
 Drowsy but arousable. Gave short answers, oriented to
person and “hospital”, not time. Poor short term
memory, no aphasia
 Cranial nerves: V, VII-XII intact
 Motor: 3/5 strength throughout but “poor effort” noted
 Sensory: patient reacted to pin bilaterally
 Reflexes: 1/4 and symmetrical with flexor plantar responses
 Coordination: finger-to-nose dysmetric, no tremor
 Gait: severe ataxia, could not ambulate without assistance
 T=100.7, P=123, BP=133/95, RR=19

24. Additional Testing
 Cranial CT unremarkable
 Electroencephalogram unremarkable
 Lumbar puncture:
 RBC 7
 WBC 4
 Protein 64 (nl<46)
 Glucose 85
 Gram’s stain, culture, acid-fast stain, cryptococcal
antigen, Lyme titer all negative
 Vitamin B12 1750 (nl>250), folate 11 (nl>6), copper 133 (nl
80-163) looking for Wilson’s Disease

25. Patient’s Axial FLAIR MRI

26. Cranial MRI Interpretation
“Bilateral symmetric, nonenhancing T2 signal abnormalities
in the thalami, periaqueductal gray matter and
hypothalamus. Diffusion weighted MRI unremarkable”
Diagnosis: highly suggestive of variant Creutzfeldt-Jakob
Disease (vCJD). Most likely human case of Mad Cow
Disease.
CDC contacted. No other cases reported in US. The three
known US cases had all lived in England prior to moving to
US.

27. Final trip to hospital
 Diagnosed with variant Creutzfeldt-Jakob/Mad
Cow Disease (vCJD/MCD) and discharged home
to die. Life expectancy several months
 Two weeks later returned to ER with
hypotension, tachycardia, respiratory
distress, unresponsive
 Pronounced dead from cardiopulmonary arrest
in ICU 12 hours later at age 22

28. Politics of Mad Cow Disease
 South Korea banned importation of US beef in 2003
because of fears of human transmission of the prion that
causes mad cow disease
 Several days before this patient was diagnosed with vCJD
the South Korean prime minister signed an agreement with
the US government to end the ban, without input from the
general public
 Once this case went public, 10,000 South Koreans held
protests for 40 days, leading to the resignation of 9
ministers
 The agreement was upheld but with an amendment that
the US would randomly test 1% of cows in perpetuity
because of this case

29. Autopsy
 Post mortem brain biopsy specimen sent to National Prion
Disease Pathology Surveillance Center at Case Western
University
 Western blot and histopathology did not show prion disease
 Focal petechial hemorrhages and focal inflammation of small
vessels and increased cellularity and disorganization of the
vessel walls in the pontineperiventricular region and
mamillary bodies
 Acute petechial hemorrhages, severe edema and relative
neuronal preservation
 Acute Wernicke’s encephalopathy due to thiamine deficiency

30. Wernicke’s Encephalopathy
 Due to thiamine (vitamin
B-1) deficiency
 Carl Wernicke, a Prussian
neuro-pathologist, first
reported a case in 1881 as a
triad of acute mental
confusion, ataxia, and
ophthalmoplegia
 Korsakoffamnestic
syndrome: memory loss
and confabulation in
survivors of Wernicke’s

31. Wernicke’s Encephalopathy
 Associations
 chronic alcoholism
 prolonged starvation
 hyperemesisgravidarum
 bariatric surgery
 HIV-AIDS
 healthy infants given the wrong formula
 Carbohydrate exposure a common trigger

32. Wernicke’s Encephalopathy:
Ocular Abnormalities
 Signs:
 Nystagmus
 Bilateral abduction palsies
 Conjugate gaze palsies
 Less frequently noted are pupillary abnormalities
such as sluggishly reactive
pupils, ptosis, scotomata, and anisocoria

33. Summary
 AION, PION, CRAO or diplopia with headache >50 years of
age, get stat ESR and non-cardiac CRP even if optic disc
normal (PION). Start steroids as soon as GCA
suspected, “shoot first and ask questions later”.
 “Rule of the III nerve”: pupil sparing complete III in
vasculopath, OK to watch pupil. Progressive III or incomplete
III or pupil involved III, get stat MRI and MRA, then perhaps
CTA and LP.
 Abnormal eye movements, ataxia and confusion= Wernicke’s
until proven otherwise. Bariatric surgery #1 cause, severe
alcoholism is now #2.

34. Thank You
David M Katz, MD
New Yorker 5/16/12