glazed (vision) and confused
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He had been well until 3 months earlier when he
months after the headaches started he becameconfused and forgetful. He forgot the code for hishouse alarm and how to use a cellular phone. Hehad an episode when he awoke confused and then
and trouble walking due to hip pain.He was evaluated by a neurologist, endocrinolo-
gist, otorhinolaryngologist, and psychologist prior
Laboratory testing during his illness included
lipid panel, and iron studies. Lead and arsenic wereundetectable. Thyroid studies were normal. Testos-
examination revealed 0 white blood cells(wbc)/mL,40 red blood cells(rbc)/mL, 76 mg/dL protein, 64mg/dL glucose, negative venereal disease researchlaboratory, no cryptococcal antigen, and no malig-
strated an opacified left frontal sinus and noparenchymal abnormalities. Repeat MRI of the
SURVEY OF OPHTHALMOLOGY VOLUME 55 NUMBER 2 MARCHAPRIL 2010had brief loss of consciousness with his eyes rolledback. He had no recollection of this event. Thevisual symptoms started 1 week later. Review ofsystems included a 45-pound weight loss attributedto medication, occasional dizziness, diffuse pain,
nant cells. Electroencephalogram (EEG) performedafter his transient loss of consciousness did notreveal epileptiform activity. Echocardiogram wasunremarkable.Magnetic resonance imaging (MRI) of the brain
two weeks after the onset of headaches demon-had flu-like symptoms of fever, fatigue, and malaisefor several days followed by the onset of severefrontal headaches without phonophobia or photo-phobia. One month after the headaches started hedeveloped depressed mood and anxiety. Three
terone was 132 (normal 241--827). Lyme and rapidplasma reagin (RPR) testing were negative. Lumbarpuncture 1 month after the start of headaches didnot provide any relief. Cerebrospinal fluid (CSF)fields. He denied double vision or positive visualphenomena. He had had a normal screeningophthalmologic examination 4 months before.
normal complete blood count, basic metabolicpanel, liver studies, B12, folate, urinalysis, fastingmic consultation for progressive blurred vision over2 weeks associated with black spots in all visual
headache and once after the episode of losingconsciousness.A 60-year-old man presented for neuro-ophthal- 201All rigCase Report to his neuro-ophthalmology referral. He was admit-ted to the hospital twice: once for evaluation ofCLINICAL CHALLENGPETER SAVINO AND HELEN DANESH-MEY
Glazed (Vision) and ConfuHeather E. Moss, MD, PhD,1 Grant T. Liu,
1Division of Neuro-Ophthalmology, Departments of Neurolothe University of Pennsylvania School of Medicine, Philade
(In keeping with the formatthe abstract and key words169
0 by Elsevier Inc.hts reserved.ESR, EDITORS
ed,1 and Josep Dalmau, MD, PhD2
and Ophthalmology; and 2Department of Neurology,ia, Pennsylvania, USA
a clinical pathologic conference,pear at the end of this article.)0039-6257/10/$--see front matterdoi:10.1016/j.survophthal.2009.03.008
decreased attention, poor effort, and labile affect. Hewas npresi5minconta
170 Surv Ophthalmol 55 (2) March--April 2010 MOSS ET ALbrain three months into his symptoms was un-changed. Computed tomography (CT) angiogramof the head was unremarkable 3 months after theonset of headaches. Chest X-ray showed no acutedisease and was stable when compared with a studyfrom 6 years prior.He was started on testosterone gel for low
testosterone 2 months into his illness without anyimprovement. Therapeutic trials for his headachesand psychiatric symptoms included antibiotics, non-steroidal anti-inflammatory agents,metoclopromide,topiramate, valproic acid, methylprednisolone, oxy-codone, clonazepam, and escitalopram. None pro-vided significant symptom relief.He had no known drug allergies. Medications
included levothyroxine, testosterone gel, flutica-sone/salmeterol inhaler, fluticasone nasal spray,montelukast, clonazepam, escitalopram, multivita-mins, folic acid, B-vitamin complex, fish oil, and
Fig. 1. Bilateral optic disk swelling; theibuprofen as needed. Past medical history includeda benign spinal cord tumor that was removed inJune 2003, hypothyroidism, and sinus surgery.He was married. He was self-employed in sales
until 3 months into his illness when he becameunable to work due to his cognitive impairments. Hehad a 25-pack an year smoking history. He quitsmoking 14 years prior to presentation. He deniedillicit drug use. Family history was remarkable forcardiac disease in both parents who died at 78 and86 years of age and an aunt with epilepsy.On examination he was normotensive weighing
228 pounds. Visual acuity was 20/80 1 ODimproving to 20/60 1 with pinhole and 20/50 2OS improving to 20/302 with pinhole. He saw only2 of 8 Ishihara color plates with the right eye, and 6of 8 with the left. Visual fields to confrontation,pupils, eyelids, and eye movements were all normal.Slit-lamp examination showed no cells in the anteriorded commands. Naming and repetition were intact.He had normal strength, sensation, coordination,gait, and deep tendon reflexes.
What are the diagnostic possibilities?
How would you proceed?
COMMENTS BY JOSEP DALMAU, MD, PHDThsubacof coon tproceningeand pup alocalioutparenlogicMRIpreseVis
an opthe rinvolinflamot oriented to city or year, he did not know thedent, and he could not recall three objects afterutes. Spontaneous speechwas perseverative andined many curses. He could not follow embed-chamber. He had bilateral optic disk swelling andbilateral vitreous haze due to vitritis (Fig. 1).On neurological examination he was agitated, with
treous haze accounts for the poor view.is is the case of a middle-aged man withute cognitive decline, visual changes, and lossnciousness starting after a febrile illness. Basedhis history a central nervous system (CNS)ss with brain parenchymal and/or leptome-al involvement causing functional impairmentossibly seizures is suggested. A negative work-t this juncture should not distract from thiszation. A normal interictal EEG does not ruleseizures unless an event is captured andchymal inflammation causing clinical neuro-al compromise may be below the resolution ofand CSF sampling, particularly early in thentation of many leptomeningeal processes.ual acuity changes and color vision loss suggesttic nerve process with or without involvement ofetina; identification of disk swelling confirmedvement of the optic nerve. The vitritis implies anmatory, infectious, or neoplastic etiology. The
2mL, 55 mg/dL glucose, 110 mg/dL protein, nomalignant cells on cytology, and no monoclonal
What is your most likely diagnosis?
COMMENTS BY DR. DALMAU
Although the identification of a mixed popula-tion of T- and B-cells with possible expression ofCD43 in the vitreous biopsy may have suggested anocular lymphoma with CNS involvement, none ofthe subsequent studies, including CSF analysis andflow cytometry, supported this diagnosis. Moreover,expression of CD43 has been reported in non-neoplastic inflammatory disorders. Detection ofthyroglobulin and TPO antibodies is often iden-tified in patients with Hashimoto thyroiditis(a frequent cause of hypothyroidism), other thyroidand autoimmune disorders, as well as in a smallnumber of normal individuals. Our patient did nothave thyroid dysfunction, and the ophthalmologicand MRI findings did not suggest Hashimotoencephalitis, an ill-defined steroid-responsive en-cephalitis that occurs in association with thyroglob-ulin and thyroperoxidase antibodies. In contrast,the asymmetric T2 hyperintensity involving themedial temporal lobes in association with lympho-cytic pleocytosis in the CSF and rapidly progressivebehavioral change and memory deficits are highly
GLAZED AND CONFUSED 171population on flow cytometry.EEG showed diffuse slowing without epileptiform
activity.BrainMRI showedbilateral (left greater than right)
hippocampal T2 hyperintensity with mild associatedrestricted diffusion and no enhancement (Fig. 2).These findings were not seen on direct comparisonwith the MRI performed 2 weeks earlier.Serological testing for paraneoplastic antibodies
revealed the presence of antibodies to collapsin-differential diagnosis of a combined CNS and opticnerve process with vitritis includes CNS lymphoma,herpes simplex virus, syphilis, vasculitis, sarcoidosis,and paraneoplastic syndromes.Considerations for further work-up include re-
peating the lumbar puncture and MRI brainimaging as well as serological testing for markersof inflammation and paraneoplastic antibodies.Vitritis offers the possibility of tissue diagnosis withminimal morbidity.
Case Report (Continued)
The patient was referred to a retinal specialist,who confirmed the fundus findings. Fluoresceinangiogram did not reveal vasculitis or retinitis. Diskstaining was consistent with edema. A vitreousbiopsy OD showed mixed T and B lymphocytes withpossible aberrant expression of CD 43, consistentwith a B-cell proliferative disorder.During the week following his initial evaluation
the patient clinically declined with worseningvision, more confusion, and severe nausea andvomiting. He started complaining of episodicstrange odors. He was admitted to the hospital forfurther work-up.Laboratory data included normal complete blood
count, metabolic profile, liver function tests, eryth-rocyte sedimentation rate, c-reactive protein, andB12. Thyroid stimulating hormone and free T4 werenormal, anti thyroglobulin antibodies were elevatedat 641 units/mL, and antithyroperoxidase antibodies(anti-TPO) were elevated atO3000 units/mL. Anti-nuclear antibodies were positive at 1:1280 ina pattern resembling perinuclear anti-neutrophilcytoplasmic antibody although lacked specificity