Herpes Simplex Gerhard W. Cibis, MD; John T.

\s=b\ Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infant. Clinically the dis-

appeared as whitish-yellow punctate lesions, perivascular cuffing, and hemorrhage. The antibody titer to herpes simplex rose from 1:8 on the day of admission to 1:256 on the day of death. Postease

mortem, intranuclear inclusion bodies that

were typical of those found with herpesvirus were seen in the brain and retina. Viral particles consistent with those of herpesvirus were found by electron microscopy in the brain and in the inner-nuclear and ganglion-nerve fiber layers of the retina. This demonstrates the direct infectious nature of herpetic retinitis. Hematogenous spread of the virus to the retina is presumed. (Arch Ophthalmol 96:299-302, 1978)

Flynn, MD;

Although herpes simplex

il

mon cause

Retinitis

of fatal

is

E.

Barry Davis

a com-

encephalitis

in adults and children, we believe that an associated retinitis has only been reported twice.1'-' In contrast, there are 14 instances of retinitis among 160 reported cases of neonatal herpes simplex.3 While this seeming differ¬ ence may be related to the unequal pathogenicity of Herpesvirus hominis type 1 vs Herpesvirus hominis type 2, a lack of awareness of the possibility of retinitis associated with herpes simplex encephalitis is more probable. We report the case of an 18-month-old infant with acute, fatal herpetic encephalitis and retinitis. It is the second report, to our knowledge, of the infecting virus being found in the retina by electron microscopy. REPORT OF A CASE An 18-month-old male

Accepted

infant, who was in

for publication April 14, 1977. From the Department of Ophthalmology, the Bascom Palmer Eye Institute, University of Miami (Fla) School of Medicine. Dr Cibis is now with The Children's Mercy Hospital, Kansas City, Mo. Reprint requests to The Children's Mercy Hospital, 24th at Gillham Rd, Kansas City, MO 64108 (Dr Cibis).

the 50th percentile for height, weight, and head circumference, was well until four days prior to his admission to the hospital, when lethargy and low-grade fever devel¬ oped. On the second day of his illness he had seizures. On admission to the local hospital, he had a WBC count of 12,700/cu mm and seven monocytes per cubic milli¬ meter of CSF, with a glucose content of 85 mg/100 ml and a protein content of 105 mg/100 ml. During the next two days his condition worsened, and extensor tendon hyperreflexia and Cheyne-Stokes respira¬ tion developed. He became comatose and Memorial was transferred to Jackson Hospital. A lumbar puncture at that time revealed 219 WBCs, with 63% monocytes in the CSF. The protein content was 189 mg/ 100 ml. His peripheral WBC count was 9,700/cu mm. The patient's respiration was assisted mechanically. An EMI scan showed a left temporal lobe lesion that was interpreted as hemorrhage. On the eighth day of illness, the EEG showed no cortical function. The clinical diagnosis was en¬ cephalitis, probably caused by Herpesvirus hominis. On the ninth day of illness, indi¬ rect ophthalmoscopy showed multiple, whitish-yellow, punctate retinal lesions and perivascular sheathing near the ora serrata superiornasally in each eye (Fig 1 through 3). The retinitis spread posterior to the equator during the next three days. Perivascular hemorrhages developed (Fig 2 and 3). The patient died on the 14th day of

Downloaded From: http://archopht.jamanetwork.com/ by a University of British Columbia Library User on 06/16/2015

Fig 1.—Small yellowish-white punctate retinal lesions. These represent areas of focal retinal necrosis with overlying inflamma¬ tory cells in vitreous.

Fig 2.—Perivascular sheathing with inflammatory cells and hemorrhage in temporal periphery of left eye. This vessel can be identified in calotte (see Fig 3).

Fig 3.—Temporal calotte of left eye showing perivascular inflammatory cell infiltrates and hemorrhage.

Fig 4.—Brain tissue showing round to polyhe¬ dral viral particles with dense osmophilic core. Tissue was deparaffinized (original magnification

10,800).

area of full-thickness retinal necrosis. There is inflammatory cell infiltrate in choroid beneath and in vitreous, above area of retinal necrosis (original magni¬ fication 4).

Fig 5—Peripheral

Downloaded From: http://archopht.jamanetwork.com/ by a University of British Columbia Library User on 06/16/2015

illness. Antibody titer to herpes simplex virus rose from 1:8 on the day of admission to 1:256 on the day of death. The left eye was enucleated 24 hours after death.

AUTOPSY FINDINGS

Findings from an autopsy revealed cortical edema and necrosis with frontal lobe and brain stem hemor¬ rhage. Light microscopy of the brain

showed Cowdry's type A intranuclear viral inclusion bodies. Electron mi¬ croscopy of the brain showed viral particles consistent with herpes sim¬ plex (Fig 4). The left eye was fixed in glutaraldehyde for light microscopy and postfixed in osmium tetroxide for electron microscopy. The globe was sectioned vertically. The clinically visible perivascular sheathing and

same area as in Fig 5. Retinal necrosis is centered around blood vessel. Viral intranuclear inclusion bodies (Fig 7) were most common in inner nuclear layer adjacent to such areas of necrosis (original magnification x 10).

Fig 6.—Magnified view of

Fig 7.—Intranuclear viral inclusion body (arrow) with margination of nuclear chro¬ matin of cell, (hematoxylin-eosin, original magnification 40).

hemorrhage were identifiable calotte (Fig 3).

in the

MICROSCOPIC PATHOLOGY

Light microscopy showed areas of normal retina near the posterior pole. Areas of full-thickness inflammatory retinal necrosis (Fig 5 and 6) were present peripherally. There were in¬ flammatory cells in the vitreous over¬ lying and in the choroid beneath these necrotic foci. These areas of necrosis appeared to correspond to the yellow¬ ish-white punctate lesions that were seen clinically. Cells that had margination of chromatin and that contained intranuclear inclusions were scattered about the areas of necrosis. They were most prominent, however, in the bipolar cell layer adjacent to the necrotic foci. They were less common in the nerve fiber or ganglion cell layer. No intranuclear inclusions were found in the choroid. A rare inclusion body was seen in vessel endothelial cells (Fig 7). A peripheral vessel with an intravascular fibrin clot had been seen clinically as a white occluded vascular strand. Perivascular hemor¬ rhage and round-cell infiltrates were present (Fig 8). The optic nerve was free of any inflammatory cells. Viral particles consistent with herpes sim¬ plex virus were found by electron microscopy in the brain (Fig 4), and in

Fig 8.—Perivascular inflammatory cell sheathing near posterior pole relatively normal retina (original magnification 25).

Downloaded From: http://archopht.jamanetwork.com/ by a University of British Columbia Library User on 06/16/2015

in

area

of otherwise

part, neonatal herpetic encephalitisretinitis, has always been whether the virus

spreads via the blood

stream

or

along the nerves and if the involve¬ ment of the second eye is a direct infection or an immune response. "7 We believe that the first histopath¬ ologic description of presumed herpet¬ ic retinitis was by Cogan et al," who felt that the isolated retinitis in their case was most compatible with an immune process. Cibis3 came to a similar conclusion because no or¬ ganisms could be found in the necrotic retina of his patient, even though inclusion bodies were readily found in the brain and herpes simplex virus type 2 was cultured from brain and skin lesions. Electron microscopic demonstration of the virus in the retina of an adult by Minckler et al,-' and now in this case, strongly supports the direct infectious nature of herpes simplex retinitis. The foci of retinal necrosis that was centered around blood ves¬ sels, intranuclear inclusions in the endothelial cells, perivascular mononuclear cell cuffing, retinal hemorrhages, and intravascular clot¬ ting in this case suggest hematogenous

Fig 9.—Retinal cells of inner nuclear layer. Virus particles (arrows) are seen in several cells (original magnification 1,900). Inset, Virus particles from cell A. These are round to polyhedral with dense osmophilic core typical of herpesvirus (original magnification 10,800).

the retinal ganglion cell and inner nuclear layers (Fig 9). COMMENT The injection of herpes simplex virus into one eye of an animal results in retinitis that is followed by enceph-

alitis and, eight to 12 days later, by retinitis in the other eye. This much repeated classic experiment once evoked interest as a possible mecha¬ nism of sympathetic uveitis.4 The question, both in the experimental situation and in its clinical counter-

spread.

We found virus in the ganglion cellnerve fiber and inner nuclear layers. Minckler et al'3 located virus only in the retinal pigmented epithelium. Most probably, all retinal layers are capable of infection with herpes simplex virus. Since acceptance of this paper for publication, a third case of herpes simplex retinitis associated with en¬ cephalitis has been reported, and is the second case showing herpesvirus in the retina by electron microscopy." This investigation was supported by Public Health Sen-ice fellowship grant IP32 EYO508701 from the National Eye Institute, Bethesda, Md.

References 1. Pavan-Langston D, Brockhurst RJ: Herpes simplex panuveitis: A clinical report. Arch

Ophthalmol 81:783-787, 2. Minckler

1969.

DS, Mclean EB, Shaw CM,

al: and retinitis. et

Herpesvirus hominis encephalitis Arch Ophthalmol 94:89-95, 1976. 3. Cibis GW: Neonatal herpes simplex retini¬ tis. Albrecht von Graefes Arch Klin Ophthalmol 1961:39-47, 1975. 4.

Szily

A

von:

Experimentelle endogene

Infektions \l=u"\bertragungvon Bulbus zu Bulbus. Klin Monatsbl Augenheilk 72:593-602, 1924. 5. Hagler WS, Walters PV, Nahmias AJ:

Ocular involvement in neonatal herpes simplex virus infections. Arch Ophthalmol 82:169-176, 1969. 6. Pettit TH, Kimura SJ, Uchida Y, et al: Herpes simplex uveitis: An experimental study with fluorescein labeled antibody technique. Invest Opthalmol 4:349-357, 1965.

7. Martenet AC: Herpes simplex uveitis: An experimental study. Arch Ophthalmol 76:858-865,

1966. 8. Cogan DG, Kuwabara T, Young GF, et al: Herpes simplex retinopathy in an infant. Arch Ophthalmol 72:641-645, 1964. 9. Johnson BL, Wisotzkey HM: Neuroretinitis associated with herpes simplex encephalitis in an adult. Am J Ophthalmol 83:481-489, 1977.

Downloaded From: http://archopht.jamanetwork.com/ by a University of British Columbia Library User on 06/16/2015

Herpes simplex retinitis.

Herpes Simplex Gerhard W. Cibis, MD; John T. \s=b\ Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infa...
11MB Sizes 0 Downloads 0 Views