An adolescent with pharyngeal-cervical-brachial variant of Guillain–Barré syndrome after cytomegalovirus infection

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    A 15-year-old Japanese girl developed bulbar palsy and upper limb-dominant muscle weakness 2 weeks after the onset of an upper

    Brain & Development 2E-mail address: (N. Murakami).respiratory tract infection due to cytomegalovirus (CMV). Her symptoms resembled that seen in the pharyngeal-cervical-brachial variant

    (PCB) of GuillainBarre 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: GuillainBarre syndrome; Pharyngeal-cervical-brachial variant; Cytomegalovirus; Anti-ganglioside antibody; Anti-GT1a IgG antibody

    1. Introduction

    GuillainBarre 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

    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 infectionsCase

    An adolescent with pharyngeal-cerv

    syndrome after cyto

    Nobuyuki Murakamia,*, Yuzo Tomit

    Yasuki Katadaa, Ryoich

    aDepartment of Pediatrics, Koshigaya Hospital, Dokkyo University SchoobDepartment of Neurology, Dokkyo University School

    Received 27 May 2005; received in revised


    l-brachial variant of GuillainBarre

    galovirus infection

    ichiaki Kogab, Etsuro Takahashia,

    akutaa, Toshiro Nagaia

    edicine, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan

    edicine, Mibu, Shimotsuga, Tochigi 321-0293, Japan

    15 August 2005; accepted 15 August 2005

    8 (2006) 269271 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.0387-7604/$ - see front matter q 2005 Elsevier B.V. All rights reserved.


    * Corresponding author. Tel.:C81 48 965 1111; fax:C81 48 965 a variant of GBS, the PCB variant [2]. Originally, lower in PCB, but Campylobacter jejuni (C. jejuni), a gram-

    negative bacterium, has been reported as a common

  • 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

    Deve2. 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

    N. Murakami et al. / Brain &270apparent limb muscle weakness, albeit weakness of handhow 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 withgrasp. 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 patients 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 gastr