Case report
An adolescent with pharyngeal-cervical-brachial variant of Guillain–Barre
syndrome after cytomegalovirus infection
Nobuyuki Murakamia,*, Yuzo Tomitaa, Michiaki Kogab, Etsuro Takahashia,
Yasuki Katadaa, Ryoichi Sakutaa, Toshiro Nagaia
aDepartment of Pediatrics, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, JapanbDepartment of Neurology, Dokkyo University School of Medicine, Mibu, Shimotsuga, Tochigi 321-0293, Japan
Received 27 May 2005; received in revised form 15 August 2005; accepted 15 August 2005
Abstract
A 15-year-old Japanese girl developed bulbar palsy and upper limb-dominant muscle weakness 2 weeks after the onset of an upper
respiratory tract infection due to cytomegalovirus (CMV). Her symptoms resembled that seen in the pharyngeal-cervical-brachial variant
(PCB) of Guillain–Barre syndrome (GBS). Although bulbar palsy usually continues for several months in PCB, her bulbar palsy was very
mild and improved rapidly before intravenous immunoglobulin therapy was instituted. Serum anti-GT1a IgG antibody titer was elevated at
the acute phase of the disease and gradually decreased. The bulbar palsy-dominant GBS is thought to relate to anti-GT1a antibody and
Campylobacter jejuni infection in adult patients. Our Case report suggests that CMV can also induce the production of anti-GT1a antibody,
thereby resulting in PCB. When one sees acute onset bulbar palsy and limb muscle weakness, the possibility of PCB, even in children, should
be considered, thus compelling the need for serum anti-ganglioside antibody measurement.
q 2005 Elsevier B.V. All rights reserved.
Keywords: Guillain–Barre syndrome; Pharyngeal-cervical-brachial variant; Cytomegalovirus; Anti-ganglioside antibody; Anti-GT1a IgG antibody
1. Introduction
Guillain–Barre syndrome (GBS) is clinically character-
ized by an acute onset of generalized and symmetrical
muscle weakness and areflexia from peripheral nerve
involvement. In GBS-variants, however, some patients
have unusual distribution of muscle involvement: external
ocular muscle involvement with ataxia in Miller Fisher
syndrome (MFS), and oropharyngeal, neck and upper limb
muscle involvement in pharyngeal-cervical-brachial (PCB)
variant form. Although GBS is one of several post-
infectious diseases that cause limb muscle weakness, the
incidence of PCB is relatively low [1]. Ropper et al. first
reported three patients with oropharyngeal, neck and
shoulder muscle weakness and categorized the condition
as a variant of GBS, the PCB variant [2]. Originally, lower
0387-7604/$ - see front matter q 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.braindev.2005.08.004
* Corresponding author. Tel.: C81 48 965 1111; fax: C81 48 965 8363.
E-mail address: [email protected] (N. Murakami).
limbs were reported to be spared in the PCB variant [2] but
some patients may have mild leg weakness [3].
Anti-ganglioside antibody is detected in the sera of
patients with GBS and its variants, and is thought to be a
useful marker for supporting this diagnosis [4]. Anti-GQ1b
IgG antibody, which cross-reacts with GT1a, is found in
patients with MFS and GBS with ophthalmoplegia [5]. PCB
has been reported to be associated with anti-GT1a IgG
antibody, but patients with PCB often have other antibodies
such as anti-GQ1b and anti-GM1 IgG antibodies as well [6].
Because isolation of authentic GT1a ganglioside is difficult,
anti-GT1a IgG antibody is not usually investigated in many
laboratories even in patients suspected with PCB, although
other antibodies are alternatively tested.
There is no comprehensive study of antecedent infections
in PCB, but Campylobacter jejuni (C. jejuni), a gram-
negative bacterium, has been reported as a common
antecedent agent in adults with bulbar palsy-predominant
GBS [7]. Here we report the case of a 15-year-old Japanese
girl who developed PCB after cytomegalovirus (CMV)
infection and who had isolated elevation of anti-GT1a IgG
antibody.
Brain & Development 28 (2006) 269–271
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N. Murakami et al. / Brain & Development 28 (2006) 269–271270
2. Clinical observation
A 15-year-old Japanese girl, who was born by normal
delivery at 36 weeks gestation and with normal develop-
ment, noticed dysarthria 2 weeks after a common cold
resulting in rhinolalia and difficulty in swallowing. There
were no accompanying gastrointestinal symptoms. Con-
currently she developed limb weakness, preferentially
involving the upper limbs. On day 9, she was referred to
our hospital because of probable GBS. On admission, she
was conscious and afebrile. Her eye movements and
pupillary light reflex were normal. She had ciliary sign,
showing mild facial palsy. She did not have hoarseness but
she had mild dysarthria and experienced mild difficulty in
swallowing. Muscle strength assessed using the Medical
Research Council (MRC) scale was graded as follows:
neck flexors, grade 4; upper limb muscles (deltoid, biceps
brachii and triceps brachii), grade 3; and proximal lower
limb muscles (iliopsoas and quadriceps femoris), grade 4.
The triceps surae was normal in strength. Deep tendon
reflexes on the upper limbs were absent and diminished on
the lower limbs. No pathological reflexes were elicited.
She did not have tachycardia or hypertension and her
respiration was normal. Sensory disturbance or cerebellar
ataxia was not found.
Routine blood chemistry revealed normal findings.
Serum anti-CMV IgG and IgM antibodies were examined
serially using commercially available ELISA kit, Cytome-
galo IgG, IgM (II)-EIA ‘SEIKEN’ (Denka Seiken, Tokyo,
Japan). On day 16 anti-CMV IgG antibody activity was
undetectable (less than 2 EIA-value; normal, less than 2),
but on day 23 it was increased to 34.6 EIA-value, indicating
seroconversion although anti-CMV IgM antibody activities
were undetectable. Anti-C. jejuni antibody was negative.
Anti-Epstein-Barr virus nuclear antigen (EBNA) antibody
was positive. Cerebrospinal fluid was normal with 36 mg/dl
protein and 2/3 cell count. We examined IgG and IgM
antibodies against GM1, GM1b, GM2, GD1a, GalNac-
GD1a, GD1b, GD2, GT1a, GT1b, and GQ1b using an
enzyme-linked immunosorbent assay as described else-
where [7]. Anti-GT1a IgG antibody was detected (titer,
4000; normal, less than 500) in her serum obtained on day
12. No other antibody was found. Although motor and
sensory nerve conduction velocities were normal, conduc-
tion block was demonstrated in the ulnar and peroneal
nerves bilaterally on day 15.
By day 14, her dysarthria had resolved but she still had
upper limb-dominant muscle weakness; this prompted us to
start intravenous immunogloblin therapy on day 17. After
the treatment, lower limb muscle weakness gradually
improved and normalized by day 25, while deep tendon
reflexes on the lower limbs were still hypoactive. She
gradually recovered upper limb muscle strength by day 34
but hypoactive deep tendon reflexes remained protracted.
Two months after the onset of the disease, she had no
apparent limb muscle weakness, albeit weakness of hand
grasp. Reduction of anti-GT1a IgG antibody titer to normal
level (less than 500) was seen three months after the onset.
At 15 months after the outset of the disease, muscle strength
was fully recovered as she regained normal hand grasp;
however, she still could not run as fast as before. Deep
tendon reflexes were normal.
3. Discussion
In 1986, Ropper described three patients with orophar-
yngeal, neck and shoulder muscle weakness and diagnosed
them as having a variant of GBS: pharyngeal-cervical-
brachial variant (PCB) [2]. In their cases, the lower limbs
were spared, and this was initially thought to be a diagnostic
hallmark for this variant [2]. However, some patients were
later described to have mild lower limb muscle weakness
[3]. Similarly our patient’s muscle weakness was upper
limb-dominant with mild thigh muscle weakness. In PCB,
bulbar palsy is noticed from the early stage of the disease
and improves in a few months. In our patient, bulbar palsy
was the initial symptom and improved rapidly. Although her
muscle involvement was compatible with the PCB, her
bulbar symptom was milder. Moreover our patient was
younger than those reported previously [2,3,6,8]. Therefore,
we initially could not ascertain the diagnosis of PCB from
her clinical symptoms alone.
GBS is one of several autoimmune disorders and is often
preceded by an infectious illness including upper respiratory
and gastrointestinal infection. A recent study has suggested
that C. jejuni, CMV Ebstein-Barre virus and Mycoplasma
pneumoniae are trigger agents for GBS [4]. In our patient,
CMV was thought to be the cause of the upper respiratory
tract infection 2 weeks before the onset of the disease
as evidenced by seroconversion against CMV. Although
anti-GM2 IgM antibody is reported to be often present in
CMV-associated GBS [4], it was not seen in our patient;
instead, she had anti-GT1a IgG antibody. GT1a ganglioside
was reported in human cranial nerves including glossophar-
yngeal and vagal nerves [9]. Therefore, anti-GT1a IgG
antibody may play a pathogenic role in the development of
bulbar palsy in PCB. Interestingly, Koga et al. reported that
all GBS patients with GT1a-specific IgG antibody had
positive serology for recent C. jejuni infection [7], which
was absent in our patient. This is the first report of PCB
associated with CMV infection although it remains unclear
how CMV infection induces the production of anti-GT1a
IgG antibody and thereby causing PCB.
All reported patients with the PCB were over 20 years
old [2,3,6,8], except for two patients described by Ropper et
al. [2] and MacLennan et al. [10]. We should therefore,
consider PCB as a differential diagnosis when confronted
with patients, including children, who present with
sudden onset bulbar palsy and limb muscle weakness.
N. Murakami et al. / Brain & Development 28 (2006) 269–271 271
The anti-GT1a IgG antibody assay indeed can be valuable
in the diagnosis of patients with PCB.
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