Graefes Arch Clin Exp Ophthalmol

(2005) 243:175177
S HORT COMMUNI CAT I ON
Isabel M. Oberacher-Velten
Jost B. Jonas
Anselm Jnemann
Barbara Schmidt
Bilateral optic neuropathy and unilateral tonic
pupil associated with acute human herpesvirus
6 infection: a case report
Received: 11 March 2004
Revised: 17 June 2004
Accepted: 19 June 2004
Published online: 10 September 2004
Springer-Verlag 2004
I. M. Oberacher-Velten (
)
) J. B. Jonas
A. Jnemann
Department of Ophthalmology
and University Eye Hospital,
University of Erlangen-Nrnberg,
Schwabachanlage 6, 91054 Erlangen,
Germany
e-mail: isabelvelten@web.de
Tel.: +49-6723-602882
Fax: +49-6722-502700
J. B. Jonas
Department of Ophthalmology
and University Eye Hospital Mannheim,
University of Heidelberg,
Theodor-Kutzer-Ufer 1-3,
68135 Mannheim, Germany
B. Schmidt
Department of Virology,
University of Erlangen-Nrnberg,
Schlogarten 4, 91054 Erlangen, Germany
Abstract Background: Human her-
pesvirus 6 (HHV-6), a widespread
virus and causative agent of exan-
thema subitum in children, has been
associated with a number of neuro-
logic 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 ju-
venile diabetes for 5 years. One
week after onset of intravenous anti-
viral therapy with foscarnet, disc
edema subsided, and tonic pupil re-
action 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 6
Optic neuropathy Disc edema
Tonic 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 ill-
ness in infants and in some infants is associated with
febrile convulsions [6]. Two distinct variants of HHV-6
HHV-6A and HHV-6Bhave been described, the B
subtype commonly being responsible for primary infec-
tion 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
1.00); intraocular pressure was 17 mmHg and 19 mmHg. Perim-
etry showed bilateral centrocecal scotomata. Ocular motility, cor-
neal esthesiometry, and exophthalmometry were normal. There was
DOI 10.1007/s00417-004-0986-8
176
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 de-
posits in the macular region. Apart from these morphological dis-
orders, there were no microaneurysms, dot and blot hemorrhages,
cotton wool spots, or intraretinal microvascular abnormalities as
signs of nonproliferative diabetic retinopathy. No other morpho-
logical abnormalities could be found in either eye. Blood testing for
connective tissue disease, syphilis, Borrelia, human herpesviruses
15 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. Mag-
netic 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 posi-
tive) on repeated examinations consistent with an acute infection or
reactivation of HHV-6. The virus could not be detected in cere-
brospinal fluid, blood, or bone marrow by polymerase chain reac-
tion. 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 im-
proved 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.
Discussion
A number of studies have suggested that the central
nervous system can be a site for persistent HHV-6 in-
fection [1, 3, 4, 6, 7]. Challoner et al. [1] described pla-
que-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 hippo-
campal 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 lym-
phoma [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 in-
fection in retinas with AIDS-associated retinitis but not
in HIV-seropositive patients with normal fundus exami-
nation 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 re-
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 1.00). Perimetry showed bilateral centrocecal
scotomata.
177
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peated 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 pa-
tient, who is supposed to be immunocompromised by
his juvenile diabetes. One might argue that the disc ede-
ma and tonic pupil could have been caused by the dia-
betes. 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 con-
jecture that the optic nerve is one of the sites of HHV-6
infection. Further studies including histological investi-
gations are needed to evaluate the role of HHV-6 in
disorders of the optic nerve and orbit, which has thera-
peutic consequences.
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