Download Introduction: James Goodwin, MD (Attending)

August 20, 2008
Introduction: James Goodwin, MD (Attending)
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his report highlights some challenging and interesting cases within the field of NeuroOphthalmology. All three cases illustrate clinical presentations that were atypical for the
eventually diagnosed conditions. Together, these cases highlight some of the problems
encountered in diagnosing neuro-ophthalmological disorders with unusual presentations and the
differential diagnosis of diseases that share overlapping symptoms.
Field defects: Jessica Wong, MD (Resident)
A
51-year-old African American woman was referred for evaluation of
questionable bitemporal visual field defect. She complained of
reduced peripheral vision in both eyes for a year, she reported that the
symptoms were worsening and were causing difficulty with driving. She
denied that there were any changes in her central vision, but complained
of occasional mild, diffuse, frontal headaches. She was initially seen in
2007 for chalazion and was found to have borderline elevated intraocular
pressure and visual field defects in both eyes. However, fundus exam
and nerve fiber layer analysis were inconsistent with the location and
extent of the visual field loss. The field defects seemed to be bitemporal
yet the CT scan showed only partially empty sella. Her exam by a
neurologist was normal. It was considered that she possibly had an optic
chiasm lesion, an atypical stroke or demyelinating disease; however MRI
did not confirm any of these. She was also seen by endocrinology, but nothing remarkable was
found.
Previous ocular history. The patient had a history of visual defects in both eyes as noted above,
and was suspected of having glaucoma. She was a contact lens wearer and a color deficiency in
both eyes was noted incidentally 10 years ago. The patient had a history of hypertension,
hyperlipidemia, and partially empty sella. She was on Combigan, Lumigan, Benicar, and Zocor.
Family history included glaucoma, hypertension and diabetes mellitus, but no cancer.
Visual exam. The patient's right eye visual acuity was 20/40 and left eye 20/30. She could identify
1/11 Ishihara with each eye, pupils were normal as was ocular motility. Applanation (Goldmann)
tonometry measured 15 for the right eye and 16 left. Slit lamp exam showed vitreous floaters in
both eyes. Differential diagnoses included conditions that produce arcuate visual field defects,
including lesions of the optic nerve (such as ischemic optic neuropathy, glaucoma, papilledema,
coloboma, compressive tumor or aneurysm, sarcoid, lymphoma or trauma), diseases of the retina
(branch retinal artery occlusion, branch retinal vein occlusion, coloboma), or a lesion in the visual
cortex (occipital). Bitemporal visual field defects were also considered as a marker for chiasmal
lesions (congenital defects, inflammation, vascular lesions or tumors particularly suprasellar
tumors, such as pituitary hyperplasia or tumors).
Fundus exam showed that the optic disc was normal in contour and color and the cup was not
enlarged. Retinal arterioles were extremely attenuated, particularly the lower arcuate branches,
and the veins were normal. She had a blunted foveal reflex and bone spicules nasally in the right
eye as well as inferiorly in the left eye. The patient was diagnosed ultimately with retinitis
pigmentosa based on fundus appearane and visual field findings.
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Blurry vision and depression: Brittany Osgood, MD (Resident)
A
63-year-old woman presented with blurry vision for approximately the previous 3-months. The patient had a
history of severe depression for over 10 years (but no prior mental health issues); during the visit she displayed
blunted affect and had difficulty giving a clear history. She had been on Wellbutrin and Celexa in the past, but was
now on Effexor and Abilify.
She reported that she had LASIK in both eyes 5 years ago, but that she still needed glasses afterwards. The
patient also reported having had a hip replacement. She had previously been working as a legal secretary, but
was unable to do so at the time of the appointment because of her vision difficulties. She had been seen by an
ophthalmologist who told her the exam was within normal limits and changed her reading prescription. After
seeing another ophthalmologist, she was eventually referred to Dr. Goodwin for further evaluation. At the initial
exam, her best corrected visual acuity was count fingers at 1 foot in the right eye and count fingers at 6 feet in the
left. Her intraocular pressure was 16 and 17 in the right and left eyes, respectively.
Her pupils were reactive, 5 to 3 in both eyes, but a 0.6 log right eye relative afferent pupillary defect (rAPD) was noted. She could identify 0/11
Ishihara plates with the right eye and 1/11 with the left; extraocular movements were full. Slit lamp exam was unremarkable. Octopus visual
fields showed complete loss of sensitivity throughout the central field of the right eye. Goldman visual fields were then performed,
which showed bilateral central scotomas in all quadrants extending out to approximately 20 degrees. A homonymous right inferior quadrant
defect was also noted which extended to the periphery. Slit lamp exam was unremarkable and dilated fundus exam was within normal limits,
with no nerve pallor.
Plan. To understand the etiology of the visual field defects and +rAPD, imaging was needed and an MRI was ordered. The MRI showed a
large homogenously enhancing extra-axial mass that was centered within the planum sphenoidale, with base along the dura consistent with
meningioma. The mass caused inferior displacement of the chiasm (6.1cm by 6.4cm by 4.7cm), as well as significant compression of the
frontal lobes bilaterally.
Follow-up. The patient was admitted to Northwestern University Hospital (her primary care doctor was an attending there) for neurosurgical
care. The lesion was resected in early May of 2008. At the follow-up appointment at the IEEI one month later, a marked change in her
personality was noted. She appeared well put-together, conversant, with remarkably changed affect from the first appointment. Her best
corrected visual acuity was 20/40 right eye, and 20/70 in the left eye. Her pupils were reactive, 4 to 2 in both eyes, no rAPD. She was able to
discern 1/11 and 0/11 color plates. Visual field testing showed scattered areas of depression in both eyes, but overall, there was much
improvement. Slit lamp exam continued to be unremarkable, and dilated fundus exam showed a slight temporal pallor of the optic discs. Two
months later, her best corrected visual acuity was 20/25 and 20/40. Repeat MRI demonstrated dramatic improvement with modest cavitary
residual encephalomacia and a tumor-free chiasm. Visual fields continued to display some areas of low sensitivity in the right eye, and a slightly
Background on Parasellar meningioma
Among patients with primary brain tumors, approximately 15-20% have meningiomas. Women outnumber men in terms of incidence of the disease,
and it typically affects women in their 60s. 40% of intracranial meningiomas are localized to the anterior skull base, with parasellar meningiomas
specifically accounting for approximately 10%. Meningiomas are typically benign and do not tend to spread aggressively unless they recur after
treatment (Mendenhall, et al., 2004). They are often asymptomatic, and can remain undiagnosed until the visual system is implicated (Chicani & Miller,
2003).
Parasellar meningiomas typically press on the optic nerve, optic chiasm, or the optic tracts (Behehani, et al., 2005; BJO). They arise from tuberculum
sella, planum sphenoidale, or anterior clinoid processes. The etiology is often idiopathic; however, there appears to be a genetic predisposition (chr 22
abnormalities) involved in some and others may occur secondary to radiation exposure (particularly among women) or other environmental causes.
There is currently ongoing research investigating potential hormonal risk factors as another potential etiologic factor.
Treatment. Therapy involves resection and/or radiation, after which the visual recovery is often dramatic. Although surgery is the treatment of choice
for meningioma, complete removal is complicated by the size and location as well as the involvement of specific brain areas or major blood vessels.
The ophthalmologist's role in care after resection is key to ensuring vision is monitored with regular exams and visual field testing. This is particularly
important given the recurrence rates: 5% recurrence rate at 5 yrs, 10% at 10 yrs, 32% at 15yrs (Mirimanoff, et al., 1985).
Diplopia and ptosis: Sing Your Li, MD (Resident)
A
68-year-old African American woman was referred to
Neuro-ophthalmology due having experienced vertical
binocular diplopia for one month and bilateral progressive
ptosis which was reportedly worse on the left side. The
patient denied any fluctuation in symptoms throughout the
course of the day and denied any improvement with rest.
The patient’s past medical history was significant for
hypertension, rheumatoid arthritis, GERD, and vertigo. She
had cataract surgery in both eyes, but had no other
significant ocular history. She was allergic to Penicillin, and
was on aspirin, Diovan, Meclizine and Prevacid.
Exam. Initial considerations as to the cause of her symptomatology included: nuclear
third nerve palsy, and ocular myasthenia gravis. The former was ruled out because the
MRI was reportedly negative. After one week of taking pyridostigmine (Mestinon), she
reported that she was responding well to the medication and that her diplopia had
resolved. Repeat brain MRI and MRA were negative and she was sent to her
ophthalmologist for a myasthenia gravis panel. She was seen in the Neuroophthalmology clinic a month later. Her diplopia remained resolved; the left eye ptosis
was stable, if not improved. However, her right eye ptosis had worsened.
The eye exam showed her visual acuity for near with +2.75 adduction was 20/25 in
the right eye and 20/20 in the left. Her pupils measured 2 mm to 1 mm both eyes with
no relative afferent pupillary defect. She demonstrated ptosis of both eyes: palpebral
fissure measured 2mm in the right, and 5mm left. Slit lamp exam was unremarkable.
Ptosis did not improve after resting with eyes closed. Her extraocular movements,
however, had worsened significantly. The patient had only minimal adduction (20%)
and depression (10%) in the right eye, and only abduction (100%) in the left eye. Her
subjective report of an improvement in her diplopia was because of near-complete
ophthalmoplegia.
Although the patient’s symptoms were consistent with ocular myasthenia gravis, the
tests for MG were negative and the ptosis did not remit with rest, a finding which is
atypical for OMG cases. Other diagnoses that were considered included the following:
Progressive Supranuclear Palsy (the patient lacked the characteristic axial rigidity)
Complete Progressive External Ophthalmoplegia (the patient lacked the characteristic
symmetry in symptoms), Oculopharyngeal Dystrophy (there was no complaint of
dysphagia), Eaton-Lambert syndrome (the patient had no history of carcinoma and
ocular muscles are usually spared), Miller Fisher Syndrome (a variant of Guillain-Barré
affecting the ocular muscles), Systemic Lupus Erythematosus (not consistent with
patient’s symptom profile), Lyme disease (patient had no history to suggest this), or
carcinomatous meningitis (patient had no history of carcinoma).
The patient was admitted to the hospital for a work-up because she reported an
episode of being out of breath and lightheadedness which, given the consideration of
myasthenia gravis, are disconcerting symptoms. Another MRI of the brain was normal,
concentric needle EMG in the left arm for work-up of generalized MG was normal,
however repetitive nerve stimulation (RNS) and single fiber EMG were both abnormal.
RNS of the left ulnar nerve showed a 9.6% decrement and on the single fiber EMG of
the left extensor digitorum communis, two of five motor units displayed an abnormal
jitter. An Acetylcholine antibody panel was high normal, but anti-MuSK antibody, Lyme
disease antibody, and ANA were negative. Her TSH was normal. Taken together,
these results were suggestive of ocular myasthenia gravis. The neurologist
recommended the patient be treated with plasma exchange (PLEX), and she received
six treatments. She was put on prednisone on the second day of plasmapheresis. Two
days into the hospital course, she began to complain of having difficulty chewing
(perhaps secondary to steroids), which improved somewhat at discharge, but never
fully returned to baseline. She regained limited movement of the right eye in all
directions, and left eye elevation also improved.
Background on ocular myasthenia gravis
Myasthenia gravis (MG) is an immunological disorder
that is characterized by muscle weakness. It may
present with ocular symptoms initially but go on to
become a systemic disease with severe consequences.
Typically, MG symptoms worsen with exercise and
improve with rest. 40-50% of patients with myasthenia
gravis present with ocular symptoms as the first signs of
the disorder, and 50-70% of those cases will progress
to generalized myasthenia gravis. Moreover, 90% of
those with MG will develop ocular symptoms (Elrod &
Weinberg, 2004). Most patients with MG experience
generalization of the disorder within 1-3 years, and only
10-30% enjoyed partial or complete remission of the
disorder. Ocular Myasthenia Gravis is limited to the
periocular muscles, whereas generalized myasthenia
gravis involves the bulbar, limb, and respiratory striated
muscles. Elrod and Weinberg (2004) recommend that
MG be considered any time ptosis, weak eye closure,
diplopia, or muscle fatigue/weakness are seen,
particularly if the symptoms seem to remit when the
patient is well-rested, or demonstrate other fluctuations.
Diagnosis. There are various laboratory tests used in
the diagnosis of generalized and ocular myasthenia
gravis: Edrophonium (tensilon) or neostigmine
(Prostigmin) has an 86-97% sensitivity for OMG, and
83% specificity for OMG. Repetitive nerve stimulation is
only 15-50% sensitive to OMG, but is 89% specific.
SFEMG is 62-100% sensitive for OMG and 89%
specific for MG and has demonstrated utility for
diagnosis when orbicularis muscle fibers are tested.
Acetylcholine receptor (AChR) antibody (Ab) (binding,
modulating, blocking) assay is 25-75% sensitive for OM
and 80-99% specific for MG. Anti-MuSK antibodies are
found in 50-70% of patients with Myasthenia Gravis
who do not demonstrate AchR antibodies. It is found in
ocular myasthenia, but is less common.
Anti-MuSK. Patients whose OMG/MG is diagnosed
with Anti-MuSK antibodies may present differently than
other OMG/MG cases. They tend to show more bulbar
involvement (masticatory, facial, lingual muscles), more
severe respiratory crises, and require a higher dose of
maintenance steroids. Anti-MuSK positive patients may
also demonstrate more intolerance to pyridostigmine,
which may include hypersensitive responsiveness such
as cholinergic crises with worsening of symptoms.
There may also be increased cholinergic side effects
such as salivation or GI problems, or there may be no
response to the drug. One line of reasoning suggests
that since anti-MuSK antibodies are less commonly
found in cases of ocular myasthenia, they may be a
marker for ocular myasthenia that is destined to
become generalized myasthenia.
Treatment. Prednisone has been shown to resolve
ptosis and diplopia for at least 2 years among 70% of
patients with ocular myasthenia gravis, and may be
more effective than pyridostigmine. It may also reduce
the likelihood of generalization among myasthenia gravis
patients who present with ocular symptoms.
Pyridostigmine is less effective for ocular myasthenia
gravis than for myasthenia gravis (approximately 50%
response rate for OMG), tends to be more effective for
ptosis than diplopia, and shows no long-term effects on
the course of the disease. Other treatments to consider
include: Azathioprine, Cyclosporin, Cyclophosphamide,
Plasmapharesis, IVIG , Mycophenolate mofetil
(CellCept), Thymectomy.
4
Background on retinitis pigmentosa (RP)
Retinitis pigmentosa is a group of hereditary retinal degenerations or dystrophies. It involves photoreceptors and pigment epithelial dysfunction or cell
loss. It is characterized by progressive visual field loss and abnormal electroretinogram (ERG). Retinitis pigmentosa can present in patients ranging in
age from infancy to late adulthood. It is confined to the eyes, and does not have any systemic manifestations. Its incidence is 1:5000 worldwide.
Secondary RP, however, is associated with single or multiple organ system diseases, such as Usher's disease.
Classification of the type of RP is dependent upon several factors. Inheritance pattern: autosomal dominant (which presents the best visual prognosis),
autosomal recessive (moderate prognosis) and X-linked recessive (worst prognosis of the three types). Age of onset: types include congenital, childhood
onset, juvenile onset, or adult onset (which can occur either early or late). Predominant photoreceptor involvement: rod-cone or cone-rod. Rod-cone
involvement is associated with ring scotoma and night vision difficulties and progressively peripheral vision decreases, sparing central vision. Cone-rod
involvement s associated with visual acuity loss, difficulties with color discrimination, and problems with day vision. Determining the location of the retinal
involvement (peripheral, sectoral, central, or pericentral) also assists in classification.
Clinical features. Patients with RP typically experience nyctalopia (night blindness) and a narrowed visual field at night which can cause them to be
more accident prone at night. They typically experience an insidious, progressive loss of peripheral visual field which can present as ring scotoma to
tunnel vision. The peripheral loss is typically symmetric, and superior visual field defects are often the first and most severe signaling early involvement of
the inferior retina. Color vision is typically good until vision deteriorates to 20/40 or worse. It may fail if the central cones are abnormal from the
beginning, which may result in impressive color vision defects even when peripheral vision is relatively good. Photopsia in RP is characterized by seeing
flashes in the mid-peripheral field which are often adjacent to scotomas, are usually stationary within the field and decrease and finally disappear as
scotomas become more dense.
References
Diagnosis. Retinitis pigmentosa is diagnosed based on fundus appearance, visual field testing, and ERG testing. ERG typically shows a loss or marked
reduction of both rod and cone signals; the rod loss is prominent. Fundus exam hallmarks include arteriolar narrowing, mottling or granularity of retinal
pigment epithelium, bone spicule-like pigment clumping, waxy pallor of the disc, general retinal pigment epithelium or choriocapillaris atrophy as the
disease progresses, macular involvement, pigmented vitreous cells, posterior vitreous detachments, posterior subcapsular cataracts, and cystoid
macular edema. Retinitis pigmentosa can present with a variety of visual field defects that differ from the typical presentation of the classis ring scotoma.
This can cause some difficulty in isolating the diagnosis with some presentations of this disorder, which may delay diagnosis.
American Academy of Ophthalmology. Retina and Vitreous. Basic and Clinical Science Course, Section 12. 2008.
Behbehani R, McElveen T, Sergott R, Andrews D, Savino P. fractionated stereotactic radiotherapy for parasellar meningiomas: A preliminary report. Br J Ophthalmol.
2008;89:130-3.
Chicani CF, Miller NR. Visual outcome in surgically treated suprasellar meningiomas. J Neuro-Ophthalmol. 2003;23(1):3-10.
Elrod R. and Weinberg W. Ocular myasthenia gravis. Ophthalmology clinics of North America, 17:3, September 2004.
Mendenhall WM, Friedman WA, Amdur RJ, Foote KD. Management of benign skull base meningiomas: A review. Skull Base. 2004;14(1):53-61.
Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza RL. Meningioma: analysis of recurrence and progression following neurosurgical resection. Journal of
neurosurgery. 1985;vol. 62(1):18-24.
Ryan, Stephen J. editor-in-chief. Retina, Fourth Edition. Volume I. Elsevier Mosby, 2006.
Yanoff, Myron and Duker, Jay S. editors-in-chief. Ophthalmology, 2nd Edition. Mosby, 2004.
UPCOMING GRAND ROUNDS
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October 29 Pediatric Ophthalmology
November 5 Retina
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2008
October 17-18 6th Annual Cornea, Cataract
and Refractive Surgery Symposium
2009
February1-3 24th Annual Winter Glaucoma
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February13-15 6th Annual Ophthalmology
Update
March 16-22 2nd Annual Illinois Eye Review
April 4 2nd Annual Retina Symposium
May2 2nd Annual Oculoplastics Symposium
June 19-20 33rd Annual Alumni Day
Editing by Cindy Veldhuis. Photos by Mark
Janowicz (unless otherwise noted). All photos are property of
UIC.
© Copyright 2008 by the Department of Ophthalmology,
University of Illinois College of Medicine. All rights reserved.