Graefe's Archive for Clinical and Experimental Ophthalmology

, Volume 243, Issue 2, pp 175–177

Bilateral optic neuropathy and unilateral tonic pupil associated with acute human herpesvirus 6 infection: a case report

Authors

    • Department of Ophthalmology and University Eye HospitalUniversity of Erlangen-Nürnberg
  • Jost B. Jonas
    • Department of Ophthalmology and University Eye HospitalUniversity of Erlangen-Nürnberg
    • Department of Ophthalmology and University Eye Hospital MannheimUniversity of Heidelberg
  • Anselm Jünemann
    • Department of Ophthalmology and University Eye HospitalUniversity of Erlangen-Nürnberg
  • Barbara Schmidt
    • Department of VirologyUniversity of Erlangen-Nürnberg
Short Communication

DOI: 10.1007/s00417-004-0986-8

Cite this article as:
Oberacher-Velten, I.M., Jonas, J.B., Jünemann, A. et al. Graefe's Arch Clin Exp Ophthalmol (2005) 243: 175. doi:10.1007/s00417-004-0986-8

Abstract

Background

Human herpesvirus 6 (HHV-6), a widespread virus and causative agent of exanthema subitum in children, has been associated with a number of neurologic disorders including cranial nerve palsies, seizures, encephalitis, meningitis, and multiple sclerosis.

Patient

A 31-year-old man presented with bilateral optic neuropathy, disc edema, and unilateral tonic pupil, which were found to be associated with acute HHV-6 infection. The patient had been suffering from juvenile diabetes for 5 years. One week after onset of intravenous antiviral therapy with foscarnet, disc edema subsided, and tonic pupil reaction was no longer detectable.

Conclusions

HHV-6 infection may play a role as a causative agent in patients with optic neuropathy and tonic pupil.

Keywords

Human herpesvirus 6Optic neuropathyDisc edemaTonic pupil

Introduction

HHV-6 is a T-lymphotropic herpesvirus, which infects almost all children by the age of 2 years and persists lifelong [3]. Prospective studies have shown that HHV-6 is the most common pathogen responsible for febrile illness in infants and in some infants is associated with febrile convulsions [6]. Two distinct variants of HHV-6—HHV-6A and HHV-6B—have been described, the B subtype commonly being responsible for primary infection in infants [3, 6]. Primary infection in healthy adults is rare. Reactivation of HHV-6 is especially found in the immunocompromised, causing serious illnesses [6]. We report on a patient with bilateral optic neuropathy/disc edema and unilateral tonic pupil associated with acute HHV-6 infection.

Case report

A 31-year-old man presented with a 4-week history of slowly progressive bilateral visual loss. The patient had been suffering from juvenile diabetes for 5 years, otherwise, his medical history was unremarkable. On ophthalmologic examination, best-corrected visual acuity was 20/60 OD (−4.25) and 20/100 OS (−4.25 to 1.0×0); intraocular pressure was 17 mmHg and 19 mmHg. Perimetry showed bilateral centrocecal scotomata. Ocular motility, corneal esthesiometry, and exophthalmometry were normal. There was an anisocoria with a larger left pupil (Fig. 1). The left pupil reaction was slow and showed light-near dissociation, irregular movements, and segmental contraction. Thirty minutes after instillation of 0.1% pilocarpine, the left pupil had contracted from 5 mm to 3 mm in diameter, whereas the right pupil had not constricted. Both eyes showed significant disc edema (Fig. 2) and intraretinal lipid deposits in the macular region. Apart from these morphological disorders, there were no microaneurysms, dot and blot hemorrhages, cotton wool spots, or intraretinal microvascular abnormalities as signs of nonproliferative diabetic retinopathy. No other morphological abnormalities could be found in either eye. Blood testing for connective tissue disease, syphilis, Borrelia, human herpesviruses 1–5 and 7, and human immunodeficiency virus (HIV) were all negative. Differential blood analysis was normal. Chest X-ray was unremarkable with no signs for sarcoidosis and tuberculosis. Lumbar puncture showed a mild lymphomonocellular activation. Oligoclonal banding was negative. Cerebrospinal fluid pressure determined during lumbar puncture was normal at 18 mmHg. Magnetic resonance imaging showed no signs of neoplasia within the optic nerves, the chiasma, or other intracranial regions. Blood testing revealed positive serum HHV-6 titers (IgG and IgM positive) on repeated examinations consistent with an acute infection or reactivation of HHV-6. The virus could not be detected in cerebrospinal fluid, blood, or bone marrow by polymerase chain reaction. Intravenous therapy with foscarnet was performed for 3 weeks. One week after onset of foscarnet therapy, oral steroids were added for 4 weeks starting with 80 mg methylprednisolone/day. One week after onset of therapy, visual acuity slowly improved and disc edema subsided. The tonic reaction of the left pupil was no longer detectable. Six weeks later, visual acuity was 20/25 OD and 20/20 OS. The right more than the left optic disc showed signs of optic nerve atrophy. The reaction of the left pupil remained normal.
Fig. 1

Left-sided tonic pupil. The patient showed an anisocoria with a larger left pupil. The pupil reaction of the left eye was slow and showed light-near dissociation, and segmental contraction. Chemical testing with pilocarpine 0.1% was consistent with a tonic pupil of the left eye

Fig. 2

a,b Bilateral optic neuropathy/disc edema. Both eyes (left OD, right OS) showed significant disc edema when the patient presented first. Visual acuity was reduced to 20/60 OD (−4.25) and 20/100 OS (−4.25 to 1.0×0). Perimetry showed bilateral centrocecal scotomata.

Discussion

A number of studies have suggested that the central nervous system can be a site for persistent HHV-6 infection [1, 3, 4, 6, 7]. Challoner et al. [1] described plaque-associated expression of HHV-6 in multiple sclerosis. Donati et al. [4] found significantly elevated levels of HHV-6 in surgical brain resections of patients with mesial temporal lobe epilepsy. HHV-6 was localized to hippocampal and temporal lobe astrocytes.

Regarding disorders of the eye, the orbit, and the cranial nerves supplying the (extra-)ocular muscles, HHV-6 has been associated with primary ocular lymphoma [2] and trochlear palsy [10]. Qavi et al. [9] found HHV-6 to be capable of infecting corneal epithelial cells in vitro causing morphological changes similar to those caused by other human herpesviruses. HHV-6 antigens were found in retinas of patients with acquired immune deficiency syndrome (AIDS) with and without AIDS-associated retinitis [8]. Fillet et al. [5] found HHV-6 infection in retinas with AIDS-associated retinitis but not in HIV-seropositive patients with normal fundus examination or in HIV-seronegative patients.

In the patient presented, acute HHV-6 infection was associated with optic neuropathy, disc edema, and tonic pupil. IgM antibodies against HHV-6 were found on repeated examinations in serum samples. The virus could not be detected in cerebrospinal fluid, blood, or bone marrow by polymerase chain reaction. This is consistent with localized reactivation of HHV-6 in the young patient, who is supposed to be immunocompromised by his juvenile diabetes. One might argue that the disc edema and tonic pupil could have been caused by the diabetes. However, no other signs of diabetic retinopathy (microaneurysms, intraretinal hemorrhages, cotton wool spots, intraretinal microvascular abnormalities) could be found. Donati et al. [4] found HHV-6 to be localized to astrocytes in patients with mesial temporal-lobe epilepsy. Based on this localization to astrocytes, one might conjecture that the optic nerve is one of the sites of HHV-6 infection. Further studies including histological investigations are needed to evaluate the role of HHV-6 in disorders of the optic nerve and orbit, which has therapeutic consequences.

Copyright information

© Springer-Verlag 2004