CASE REPORT infectious mononucleosis, complications; neuritis, optic, causes

Severe Optic Neuritis in Infectious Mononucleosis

Because the presentation and clinical features of infectious mononucleosis can be misleading in the elderly, a significant number of infections may go unrecognized. We report an unusual case of infectious mononucleosis in a 61-year-old man in whom marked visual impairment was the presenting complaint and severe optic neuritis was the only prominent finding. Confir- mation of the diagnosis was made by serologic testing for Epstein-Barr virus antibody Recovery of visual function was near complete, but optic atrophy persisted. We reviewed the English literature and collected seven cases of well-documented optic neuritis associated with infectious mononucleosis. A clinical profile of parainfectious optic neuritis is ddiscussed along with the likely pathogenesis for this complication. [Jones J, Gardner W, Newman T: Severe optic neuritis in infectious mononucleosis. Ann Emerg Med April I988;17:361-364.]

INTRODUCTION Infectious mononucleosis is a benign lymphoproliferative disorder that

typically affects young adults. 1 Most individuals more than 50 years old show evidence of previous infection with the Epstein-Barr virus (EBV) and are thus immune to any subsequent exogenous reinfection. 2 When the infec- tion does occur in susceptible older persons, they often have more severe illnesses and complications.g, 4 A significant number of these cases go un- recognized, not only because infectious mononucleosis is considered to be a disease of the young, but also because its presentation can be misleading3,4, 5

The clinical features of classic infectious mononucleosis have been well described, but only isolated reports have dealt with this disease in the geri- atric patient3, 3-6 All of these patients presented with nonspecific constitu- tional symptoms and rarely had pharyngitis, cervical adenopathy, or splenomegaly. Infectious mononucleosis was not initially considered in these patients, because of their age, until atypical lymphocytes were detected on the peripheral blood smear. Heterophil antibody titers confirmed the diag- nosis.

Not infrequently, a complication is the only clinical manifestation of in- fectious mononucleosis in the geriatric patient, s Single symptoms may so dominate the disease picture as to result in a wrong preliminary diagnosis, such as nephritis, hepatitis, or meningitis.7 In such cases, the emergency physician must be aware of the number of complications of the disease to obtain the hematologic and serologic evidence necessary for the diagnosis.

Accordingly, we report a case of infectious mononucleosis in which marked visual impairment was the presenting complaint and moderately se- vere optic neuritis was the only prominent finding. A clinical profile of para- infectious optic neuritis is discussed along with the proposed pathogenesis for this rare complication.

CASE REPORT A 61-year-old man presented with bilateral eye discomfort and blurred vi-

sion of two days duration. Both eyes were affected equally and he had no symptoms of scotoma, diplopia, or difficulty with color vision. The patient had been well until five days before, when he developed an intermittent frontal headache, progressive fatigue, and a low-grade fever of 38.1 C. He had no history of head trauma, mental status changes, neck stiffness, pharyngitis,

Jeffrey Jones, MD William Gardner, MD Tim Newman, MD Akron, Ohio

From the Department of Emergency Medicine and Infectious Disease, Akron General Medical Center, Northeastern Ohio Universities, College of Medicine, Akron, Ohio.

Received for publication April 6, 1987. Revision received November 16, 1987. Accepted for publication January 19, 1988.

Address for reprints: Jeffrey Jones, MD, Akron General Medical Center, Department of Emergency Medicine, 400 Wabash Avenue, Akron, Ohio 44307.

17:4 April 1988 Annals of Emergency Medicine 361/113

OPTIC NEURITIS Jones, Gardner & Newman

or adenopathy. He denied drug inges- tion.

Physical examinat ion revealed a temperature of 36.6 C; blood pressure, 114/70 mm Hg; pulse, 84; and respira- tions, 16. Visual acuity was 20/200 in the right eye and 20/100 in the left eye. Visual fields, color perception, and moti l i ty were normal. Fundu- scopic examination showed slight blurring of disc margins. The remain- ing cranial nerves were normal. Senso- ry, motor, and autonomic systems were normal. The neck was not rigid. The patient's oropharynx showed no evidence of infection. He had no lymphadenopathy, hepatomegaly, or splenomegaly. Jaundice or skin lesions were not evident.

Laboratory values included: erythro- cyte sedimentation rate, 24 mm in first hour; hemoglobin, 14.8 g/dL; leu- kocytes, 10,000/ram 3 (with 29% neu- trophils , 37% lymphocy tes , 25% atypical lymphocytes, and 9% mono- cytes); total serum bilirubin, 0.8 mg/ dL (normal, 0.2 to 0.8 mg/dL); alkaline phosphatase, 472 U/L (normal, < 55 U/L); SGOT, 129 U/L (normal, < 41 U/ L); SGPT, 222 U/L (normal, < 45 U/L); lactate dehydrogenase, 376 U/L (nor- mal, < 200 U/L); and a negative hepa- titis panel. Results were positive from a differential slide test for the hetero- phil antibody to EBV (monospot}, and antibody titer to EBV capsid antigen (EBVCA) was 1:40. A computerized to- mographic scan of the brain was nor- mal.

Two weeks after the onset of fever, visual acuity had decreased to count- ing fingers in the right eye and 20/400 in the left. Each optic disc was swollen with central pallor. Visual fields and motility remained intact. The remainder of the physical exam- ination was normal. Oral prednisone therapy (100 mg/day) was begun, and the dosage was tapered over six weeks. Visual acui ty improved gradually, being 20/40 in the right eye and 20/20 in the left eye two months later. There was a residual pallor of the optic discs bilaterally. Liver function tests, leuko- cyte count, and differential had re- turned to normal.

DISCUSSION Optic neuritis is a broad term de-

noting any inflammation, degenera- tion, or demyelinization of the optic nerve. 8 Loss of vision is the cardinal symptom and serves to differentiate optic neur i t i s f rom papi l ledema,

FIGURE. Causes of optic neuritis.9, lo

which it may resemble on examina- tion. 9 Other frequent ophthalmologic symptoms include blurred vision, cen- tral scotoma, and some loss of color vision. 9 There may be pain in the re- gion of the eye, especially on move- ment of the globe.

Ophthalmoscopically, hyperemia of the optic disc and distension of large veins are early signs. 9 Blurred disc margins and filling of the physio- logic cup are common. There may be marked edema of the nerve head (pap- illitis), edema of the nerve head and retina (neuro-retinitis), or no apparent abnormality (retrobulbar neuritis). 8 Flame-shaped hemorrhages may occur in the nerve fiber layer near the optic disc. 10

The most frequent cause of optic neuritis is multiple sclerosis. A diag- nosis of multiple sclerosis is even- tually made in 25% to 50% of young- er patients who have an attack of retrobulbar neuritis. 9 Other causes in- clude a wide variety of infectious, in- flammatory, nutritional, and vascular diseases (Figure). If the process is suffi- ciently destructive, the disc loses its normal pink color and becomes pale (optic atrophy)30

The earliest report of optic neuritis in infectious mononucleosis probably was by Clemens 11 in 1907, but cor- roborative details are lacking. In addi- tion to that of our patient, there are seven other well-documented descrip- tions of optic neuritis due to EBV in- fections (Table}. Additionally, there are reports of papilloedema without sig- nificant loss of visual acuity. 12-14

With the exception of our patient, all the cases summarized (Table) were between the ages of 6 and 29 years. The diagnosis of EBV infection was confirmed by rising EBV antibody titers. The majority of patients had other systemic manifestations of in- fectious mononucleosis. The onset of visual loss was in the second to fourth week after initial symptoms of the ill- ness. However, one other patient, 7 in addition to our own, had acute vision loss as the sole manifestation of EBV infection. Visual 10ss varied from se- vere bilateral involvement to moder- ate unilateral impairment. Full recov- ery of visual acuity occurred in six patients but pallor of the optic disc frequently remained. Satisfactory re- covery of vision often occurred before

Demyelinating diseases Multiple sclerosis

Viral infections Herpes zoster Infectious mononucleosis Childhood exanthems Postinfectious

encephalomyelitis

Local extension of inflammatory disease

In t raocular- chorioretinitis Orbital - - cellulitis Intracranial - meningitis,

encephalitis Sinusitis

Systemic infections and inflammation

Neurosyphilis Tuberculosis Sarcoidosis Infective endocarditis Coccidioidomycosis

Nutritional and metabolic Vitamin def ic ienc ies-

beriberi, pellagra Diabetes mellitus Dysthyroidism

Toxic Heavy metal ~--lead,

arsenia, thallium Methanol Tobacco-alcohol amblyiopia Drugs - - digitalis,

streptomycin,_ disulfiram

Hereditary optic atrophy Leber's disease Behr's syndrome Infantile optic atrophy

Vascular disease Cranial arteritis Polyarteritis nodosa Arteriosclerosis

Trauma

Idiopathic

the era of cor t icosteroid therapy, which may preclude any need for its use in this disorder.

114/362 Annals of Emergency Medicine 17:4 April 1988

TABLE. Optic neuritis associated with infectious mononucleosis

Visual Loss Patient's

Source Age (yr)

Karpe 7 20 1948

Ophthalmologic Symptoms Acuity

Decrease in color vision, CF,* OD;t blurred vision, ©D 20/20 OSt

Bonynge 22 14 1952

Decrease in acuity and color vision, blurred vision, central scotoma

Tanner 23 17 1954 Schecter 24 6 1955 F~y 8 9 1973

CF, OU

Williamson 17 29 1975

Pickens 25 18 1975

Jones 61

Pain on accommodation, blurred 20/30 OU* vision, photophobia

Blurred vision, central 20/70 OD; scotoma, OD 20/20 OS

Decreased acuity, scotoma, 1/200 OD; OD 20/20 OS

*CF indicates counting fingers. rOD, right eye; OS, left eye. ¢OU, both eyes.

Decreased acuity, 20/15 OD; central scotoma, 20/100 OS pain in orbit, OS

Pain on eye movement, 20/100 OD; decreased acuity 20/200 OS

Bilateral eye pain, CF, OD; blurred vision 20/400 OS

Fundi

Pallor of disc, papilloretinal edema, OD; normal, OS

Papilledema, splinter hemorrhages, OU

Papilledema, iritis, OU Normal

Papilloretina[ edema, OD; normal, OS

Normal

Normal

Papilledema, pallor of discs, OU

Visual Recovery

Acuity Fundi

20/20 OU Macular hyper- pigmentation, OD

20/20 OU Pallor of discs

20/15 OU Normal

20/20 OU Normal

20/20 OU Faint residual macular scars, OD

20/20 OU Normal

20/100 OD; Pallor of discs 20/2O00S

20/40 OD; Pallor of discs 2O/20 OS

Rapid r ecove ry b e g i n n i n g at the c o m m e n c e m e n t of prednisone was a feature of this case. This may have been coincidental , but o ther authors have noted dramatic improvement in neurological manifestat ions when cor- t icosteroids or ACTH were used. lsq7

T h e pathogenesis by which a viral il lness leads to subsequent optic neu- r i t is , w i t h o u t a s soc ia ted neuro log ic signs, is not well established. The pro- found loss of visual function followed by near-complete recovery in these pa- t i en t s is i nd ica t ive of a t e m p o r a r y block in conduct ion of action poten- t ials and not a structural disruption of the optic nerve a x o n s ) 8 In addit ion, the delayed onset after the ini t ial in- fection and the bilateral involvement a r e strong support for a general ized m e c h a n i s m of injury (ie, a sys temic a u t o i m m u n e demye l ina t i on ) ra ther than random, viral invasion of each optic nerve.

Selbst et al t8 suggest t ha t papi l - l edema seen f requent ly in these pa- t ients results from congestion of axo- p lasm in the unmye l ina t ed axons of the optic papilla. This congest ion is

t hough t s econda ry to i n f l a m m a t i o n associated wi th re t robulbar demyel i - na t ion of the optic nerve. 18 Further inves t igat ion is needed to de te rmine how the systemic immune response is in i t ia ted and directed pr incipal ly to the optic nerves.

The true incidence of optic neuri t is a s s o c i a t e d w i t h i n f e c t i o u s m o n o - nucleosis is undoubted ly more com- m o n than the l i t e r a tu re ind ica tes . 8 Recognition of optic neuri t is depends on a pat ient 's abil i ty to detect and ver- bal ize the s o m e t i m e s sub t l e symp- toms of reduct ion in vis ion and the clinician's abil i ty to elicit findings of decreased visual acuity, loss of visual f ie ld , and co lo r p e r c e p t i o n abnor - malit ies.

Infectious mononucleosis can be di- agnosed wi th reasonable accuracy by the presence of a typical clinical pic- ture coupled w i t h a typ ica l l y m p h o - cytos is and he t e roph i l a n t i b o d i e s ) s T h e p e r i p h e r a l b lood f i lm d e m o n - strates an absolute lymphocy tos i s in 60% of cases, and in half the patients ' atypical mononuclear cells wil l make up 10% or more of the total whi te

count. 19 These changes are diagnostic wi th a specificity of 95% or more in all cases, but wil l be slightly less spe- cific in the d i f fe ren t ia l d iagnosis of viral hepa t i t i s ) 9

The diagnosis of infect ious mono- nucleosis is conf i rmed by the detec- t i on of h e t e r o p h i l an t i bod i e s . The Monospot test is simple to use in the emergency department; it has a sen- s i t iv i ty of 80% and a spec i f i c i ty of 99%. 19 The tes t may need to be re- peated because it is negative ini t ial ly in a p p r o x i m a t e l y o n e - s i x t h of pa- t i e n t s . 20 W h e n t h e M o n o s p o t i s p o s i t i v e and a c c o m p a n y i n g b l o o d smears m e e t c r i t e r ia for in fec t ious mononucleosis , the diagnosis of EBV infection is presumed and no further diagnost ic tests are indicated.Is,19, 21 In cases that are clinically compatible wi th infectious mononucleosis but are h e t e r o p h i l n e g a t i v e , spec i f i c EBV serology should be performed.

S U M M A R Y Our case report demons t ra tes that

optic neuri t is can be the sole manifes- t a t ion of in fec t ious m o n o n u c l e o s i s .

17:4 April 1988 Annals of Emergency Medicine 363/115

OPTIC NEURITIS Jones, Gardner & Newman

Inapparent infections, atypical man- ifestations, and mul t i sys tem com- plications of EBV infection are com- mon, The favorable prognosis, fre- quency of delayed onset, and bilateral involvement of the optic nerves sup- port an autoimmune process in the pathogenesis of optic neuritis associ- ated with infectious mononucleosis.

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6. Shapiro CM, Horwitz H: Infectious mono- nucleosis in the aged. Ann Intern Med 1959; 51:1092-1097.

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8. Frey T: Optic neuritis in children: Infectious mononucleosis as an etiology. Doc Ophthalmol 1973;34:183-188.

9. Vaughan D, Asbury T: General Ophthalmol- ogy. Los Altos, California, Lange Medical Pub- lishers, 1983, p 206-211.

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16. Schnell RG, Dyck PJ, Bowie EJW, et al: In- fectious mononucleosis: Neurologic and EEG findings. Medicine 1966;45:61-63.

17. Williamson PM: Neuromyelitis optica fol- lowing infectious mononucleosis. Proc Aust Assoc Neurol 1975;12:153-155.

t8. Pochedly C: Laboratory testing for infec- tious mononucleosis: Cautions to observe in interpreting results. Postgrad Med 1987;81: 335-342.

19. White NJ, Juel-Jenson BE: Infectious mono- nucleosis hepatitis. Semin Liver Dis 1984;4: 301-306.

20. Fleisher GR, Collins M, Fager S: Limita- tions of available tests for diagnosis of infec- tious mononucleosis. J Clin Microbiol 1983; 17:619-624.

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22. Bonynge TW, Von Hagen KO: Severe optic neuritis in infectious mononucleosis: Report of case. [AMA 1952;148:933-934.

23. Tanner OR: Ocular manifestations of infec- tious mononucleosis. Arch Ophthalmol 1954; 51:229-241.

24. Shechter FR, Lipsius EI, Rasansky HN: Retrobulbar neuritis: A complication of infec- tious mononucleosis. Am J Dis Child 1955; 89:58-61.

25. Pickens S, Sangster G: Retrobulbar neuritis and infec t ious mononuc leos i s . Br Med ] 1975;4: 729.

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116/364 Annals of Emergency Medicine 17:4 April 1988