□ CASE REPORT □

Guillain-Barré Syndrome with Optic Neuritis
and a Focal Lesion in the Central White Matter
Following Epstein-Barr Virus Infection
Jae Young An, Bora Yoon, Joong Seok Kim, In Uk Song, Kwang Soo Lee and Yeong In Kim

Abstract
We report a case of Guillain-Barré syndrome (GBS) accompanied by optic neuritis and a central white
matter lesion subsequent to Epstein-Barr virus (EBV) infection. A 49-year-old man presented with visual disturbance and hemiparesis one week after developing cold-like symptoms. T2- and diffusion-weighted brain
MRI showed a high-signal intensity lesion in the left internal capsule. The patient’s visual acuity improved
during steroid pulse therapy, but his hemiparesis progressed to quadriparesis. Nerve conduction studies
showed demyelination predominant in the distal nerve terminals, consistent with GBS. Serological testing
suggested EBV reinfection. Our findings indicate that EBV-related central and peripheral demyelination can
occur simultaneously and can be successfully treated with a combination of corticosteroids and immunoglobulin.
Key words: Epstein-Barr virus, Guillain-Barré syndrome, optic neuritis, central white matter
(Inter Med 47: 1539-1542, 2008)
(DOI: 10.2169/internalmedicine.47.1224)

Introduction
There have been several reports of central nervous system
(CNS) involvement in Guillain-Barré syndrome (GBS),
which is usually associated with cytomegalovirus or mycoplasma pneumonia (1-4). Although the neurological complications of Epstein-Barr virus (EBV) infection include a wide
spectrum of clinical syndromes involving the CNS and peripheral nervous system (PNS) (5, 6), GBS accompanied by
optic neuritis (ON) and a focal lesion in the central white
matter subsequent to EBV infection is very rare.

Case Report
A 49-year-old man with arterial hypertension experienced
a visual disturbance in his right eye accompanied by right
hemiparesis upon awakening. The patient had had a cough
and low-grade fever 7 days earlier. On physical examination,
the patient had a body temperature of 36.7℃ and a blood
pressure of 135/76. Neurological examination revealed mild

right hemiparesis (Medical Research Council [MRC] grade
4). Visual acuity was light perception in the right eye. Deep
tendon reflexes (DTRs) were slightly decreased in the right
upper and lower extremities. All other neurological findings
were normal. A complete blood count showed a hematocrit
of 44.5%, a WBC count of 7.78×109 cells/μL (67.5% neutrophils, 24.6% lymphocytes, and 5.8% monocytes), and a
platelet count of 274×109 cells/μL. The results of blood
chemistry, including transaminase, were normal, as were the
chest radiograph findings. Brain magnetic resonance imaging (MRI) revealed a focal area of high signal intensity in
the left internal capsule on T2- and diffusion-weighted images, but there was no decrease in the apparent diffusion coefficient (ADC) value, and no gadolinium enhancement was
observed (Fig. 1). A test for visual evoked potential showed
no wave formation on the right side.
The CSF was clear, with an opening pressure of 17cmH2O,
WBC count of 3 cells/uL, glucose level of 72.2 mg/dL
(blood glucose of 128.5 mg/dL), and protein level of 55 mg/
dL. No microorganisms were observed on Gram- and acidfast bacilli (AFB)-stained smears or an Indian ink prepara-

１

Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Received for publication April 18, 2008; Accepted for publication May 22, 2008
Correspondence to Dr. Yeong In Kim, nuyikim@catholic.ac.kr

1539

Inter Med 47: 1539-1542, 2008

DOI: 10.2169/internalmedicine.47.1224

Fi
g
ur
e1
. Af
o
c
a
la
r
e
ao
fhi
g
hs
i
g
na
li
nt
e
ns
i
t
yo
nT2
we
i
g
ht
e
d(
A)a
nddi
f
f
us
i
o
nwe
i
g
ht
e
d(
B)
MRIwa
sno
t
e
di
nt
hepo
s
t
e
r
i
o
rl
i
mbo
ft
hel
e
f
ti
nt
e
r
na
lc
a
ps
ul
e
,whi
c
hs
ho
we
dnog
a
do
l
i
ni
um e
nha
nc
e
me
nt(
C)a
ndnode
c
r
e
a
s
ei
nt
hea
ppa
r
e
ntdi
f
f
us
i
o
nc
o
e
f
f
i
c
i
e
nt(
D)
.

tion. CSF cryptococcal antigen was negative, as was PCR
for Mycobacterium tuberculosis and herpes simplex. The
CSF concentration of myelin basic protein was not elevated,
and the IgG index was normal. Oligoclonal bands were not
detected. Tests for vasculitic markers, including serum antinuclear antibodies, extractable nuclear antigens and antineutrophil cytoplasmic antigen, were negative.
The patient was initially diagnosed with acute disseminated encephalomyelitis and treated with pulse intravenous
methylprednisolone (1 g/day for 3 days). On day 2, the
hemiparesis progressed to quadriparesis (MRC 2-3/5), and
DTRs were absent in all limbs.
Table 1 shows results of nerve conduction studies. There
was evidence of demyelination predominant in the distal
nerve terminals; motor distal latencies were substantially
prolonged in all the nerves tested with relative preservation
of nerve conduction velocities in the forearm and leg segments. Reduced median and ulnar sensory responses with
preserved sural responses were consistent with demyelination in the distal nerve segments. Figure 2 shows waveforms
in median and ulnar motor studies. Abnormal temporal dis-

persion of the distally evoked compound muscle action potentials, again, supported demyelination in the motor nerve
terminals. Serum anti-GM1, GD1, GQ1b and MAG antibodies were negative. Serologic tests for EBV were performed
by enzyme immunoassay. The patient was positive for antibodies to viral capsid antigen (VCA) IgG and IgM and EBV
nuclear antigen (EBNA) IgG and IgM, but negative for
EBV-early antigen, diffuse or restricted (EADR) IgG and
IgM antibodies. Serologic tests for CMV, C. jejuni, and M.
pneumonia were negative.
The patient was diagnosed with atypical GBS associated
with EBV infection. Treatment with intravenous immunoglobulin G (IVIgG) (0.4 mg/kg/day for 5 days) was started
on day 4. Bilateral peripheral facial palsy, dysphagia, and
mild dyspnea were noted on day 5, but the patient’s visual
acuity in the right eye improved to a finger count of 30 cm.
On day 35, the patient was able to walk without support,
and the visual acuity in his right eye improved to 0.16.

1540

Inter Med 47: 1539-1542, 2008

DOI: 10.2169/internalmedicine.47.1224

Ta
bl
e1
. Mo
t
o
ra
ndSe
ns
o
r
yNe
r
v
eCo
nduc
t
i
o
nSt
udi
e
s

Fi
g
ur
e2
. Mo
t
o
rne
r
v
ec
o
nduc
t
i
o
ns
t
udi
e
so
ft
hel
e
f
tme
di
a
na
ndul
na
rne
r
v
e
ss
ho
we
dc
o
nduc
t
i
o
n
bl
o
c
ka
ndt
e
mpo
r
a
ldi
s
pe
r
s
i
o
n.

Discussion
The clinical spectrum of neurological complications associated with EBV infection is wide, but the exact incidences
of these complications are unknown. Some studies reported
an association between EBV infection and GBS in up to
10% of cases (7, 8).
In the present case, the patient initially presented with ON
and a focal lesion in the central white matter after developing mild symptoms of an upper respiratory infection, and
progressed to areflexic paralysis, bilateral facial nerve palsy,
and autonomic dysfunction, consistent with GBS.
Brain MRI suggested that the lesion was caused by subacute infarction or demyelination. However, we thought that
this lesion was more likely to have resulted from demyelination than from subacute infarction because the MRI was performed within 10 hours after the onset of weakness. However, it was uncertain whether the initial right-sided weakness was due to the left-sided focal central white matter lesion or whether it was an early symptom of GBS.
Although infection and neurological symptoms may coincide, there was a clear correlation between the clinical
symptoms and serological findings in the present case. Serologic testing of early acute phase specimens for EBV suggested reinfection (9, 10). EBV-associated neurological disease was previously thought to occur exclusively in cases of
acute primary infection and children. However, with the re-

cent development of improved diagnostic tools, there have
been several reports of EBV-related neurological complications associated with reactivated infection in adults (11, 12).
In most of the reported cases of GBS with ON, the temporal profile of GBS differed from that of ON (1, 13). This
biphasic illness profile suggests that an autoantigen was liberated from the nervous system during the first attack and
subsequently sensitized the host to cause the second insult
(13). However, in the present case, GBS developed at the
same time as ON, which suggests that an epitope shared by
the CNS and PNS was targeted. The patient’s visual acuity
improved, but the hemiparesis progressed to quadriparesis,
and peripheral facial nerve palsy and autonomic symptoms
began to develop after steroid pulse therapy. Although the
exact mechanism is not fully understood, the pathogenesis
of ON or central white matter lesion development may differ from that of GBS.
Given the widespread prevalence of human EBV infection
throughout the world, it is likely that the burden of neurological disease associated with EBV has been underestimated. Furthermore, EBV may present atypically, and it has
been associated with a wide spectrum of neurologic diseases. EBV should be considered when a patient presents
with both CNS and PNS symptoms. Simultaneous treatment
of high-dose steroid pulse and IVIgG therapy may be more
helpful in reducing the incidence of adverse neurological
outcomes than IVIgG monotherapy in these cases.

1541

Inter Med 47: 1539-1542, 2008

DOI: 10.2169/internalmedicine.47.1224

References
1. Nadkarni N, Lisak R. Guillain-Barré syndrome (GBS) with bilateral optic neuritis and central white matter disease. Neurology 43:
842-843, 1993.
2. Ginestal RC, Plaza JF, Callejo JM, Rodriguez-Espinosa N,
Fernádez-Ruiz LC, Masjuán J. Bilateral optic neuritis and
Guillain-Barré syndrome following an acute Mycoplasma pneumoniae infection. J Neurol 251: 767-768, 2004.
3. Pfausler B, Engelhardt K, Kampfl A, Spiss H, Taferner E,
Schmutzhard E. Post-infectious central and peripheral nervous system diseases complicating Mycoplasma pneumonia infection. Report of three cases and review of the literature. Eur J Neurol 9:
93-96, 2002.
4. Igarashi O, Fujioka T, Kishi M, Normoto N, Iwasaki Y, Kurihara
T. Guillain-Barré syndrome with optic neuritis and cytomegalovirus infection. J Peripher Nerv Syst 10: 340-341, 2005.
5. Portegies P, Corssmit N. Epstein-Barr virus and the nervous system. Cur Opin Neurol 13: 301-304, 2000.
6. Conelly KP, DeWit LD. Neurologic complication of infectious
mononucleosis. Pediatr Neurol 10: 181-184, 1994.
7. Hahn AF. Guillain-Barré syndrome. Lancet 325: 635-641, 1998.

8. Winer JB, Hughes RAC, Anderson MJ, Jones DM, Kangro H,
Watkins RP. A prospective study of acute idiopathic neuropathy: II
antecedent events. J Neurol Neurosurg Psychiatry 51: 613-618,
1988.
9. Nystad TW, Myrmel H. Prevalence of primary versus reactivated
Epstein-Barr virus infection in patients with VCA IgG-, VCA
IgM- and EBNA-1 antibodies and suspected infectious mononucleosis. J Clin Virol 38: 292-297, 2007.
10. Nalesnik MA. Epstein-Barr virus. In: Laboratory diagnosis of viral
infections. Lennette EH, Smith TF, Eds. Marcel Dekker, Inc., New
York, 1999: 385-419.
11. Merelli E, Bedin R, Sola P, et al. Encephalomyeloradiculopathy
associated with Epstein-Barr virus: primary infection or reactivation? Acta Neurol Scand 96: 416-420, 1997.
12. Weinberg A, Li S, Palmer M, Tyler KL. Quantitative CSF PCR in
Epstein-Barr virus infections of the central nervous system. Ann
Neurol 52: 543-548, 2002.
13. Nikoskelainen E, Riekkinen P. Retrobulbar neuritis as an early
symptom of Guillain-Barré syndrome. Report of a case. Acta Ophthalmol (Copenh) 50: 111-115, 1972.

Ⓒ 2008 The Japanese Society of Internal Medicine
http://www.naika.or.jp/imindex.html

1542