Journal of the Peripheral Nervous System 20:32–36 (2015)

RESEARCH REPORT
When is facial diplegia regarded as a variant
of Guillain-Barré syndrome?

J. K. Kim1 , S. Y. Oh2 , E. H. Sohn3 , Y. H. Hong4 , S. M. Jun1 , and J. S. Bae5

1
Department of Neurology, Dong-A University College of Medicine, Busan, Korea; 2 Department of Neurology, Chonbuk
National University College of Medicine, Jeonju, Korea; 3 Department of Neurology, Chungnam National University College of
Medicine, Daejeon, Korea; 4 Department of Neurology, Seoul National University Boramae Hospital, Seoul, Korea; and
5
Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea

Abstract A variant of Guillain-Barré syndrome (GBS) with predominant manifestation

of facial diplegia (FD) has been described recently. This study aimed to characterize and
determine the incidence of this FD-predominant GBS variant. The clinical and serological
information of 900 consecutive patients were reviewed. In total, eight patients were
identified between January 2007 and December 2010 as having FD accompanied by
some features of GBS. These features were subjective sensory symptoms such as
distal paresthesia (7/8, 88%), albumin-cytological (A/C) dissociation (7/8, 88%), antecedent
infection (6/8, 75%), and minor nerve conduction study (NCS) abnormalities (5/7, 71%).
One patient presented with the typical NCS feature of demyelinating neuropathy. Only two
patients exhibited areflexia (2/8, 25%). None of the patients possessed any anti-ganglioside
antibodies; however, the serum of two patients was positive for anti-mycoplasma antibody
(2/6, 33%). FD variant of GBS occurred in less than 1% of our dataset. FD can be a regional
variant of GBS when it is accompanied by supporting features, such as subjective tingling,
A/C dissociation, and minor NCS abnormalities.

Key words: Guillain-Barré syndrome (GBS), variant, facial paralysis, bilateral

Introduction Nonetheless, frequent overlap with other GBS

Facial diplegia (FD) is a rare and specific clini-
cal sign that enables the discrimination of relevant
neurological disease. FD is generally attributed to
trauma, multiple sclerosis, sarcoidosis, infection, vas-
culitis, leukemia, posterior fossa tumor, or Bell’s palsy
(Teller and Murphy, 1992; Keane, 1994; Jain et al.,
2006). However, the most common etiology of FD is
Guillain-Barré syndrome (GBS) (Ropper et al., 1991).
GBS presenting with FD as a major feature has
been reported for many years (Jones, 1954; Charous
and Saxe, 1962; Rontal and Sigel, 1972; Shuaib and
Becker, 1987).
Address correspondence to: J. S. Bae, Department of Neurology,
Kangdong Sacred Heart Hospital, College of Medicine, Hallym
University, 150 Seongan-ro, Gangdong-gu, Seoul 134-701, Korea. Tel:
+(82)2-22242854; Fax: +(82)2-4786330; E-mail: lwsbae@naver.com.
features renders this variant rather obscure across the
clinical GBS spectrum. Thus, in cases suspicious of
the FD-predominant variant of GBS, various features
may accompany FD, such as paresthesia of the distal
limb, areflexia, albumin-cytological (A/C) dissociation,
and minor nerve conduction study (NCS) abnormalities.
The aims of this study were to determine the
incidence of either isolated FD (FDi) or FD plus other
GBS features (FDp) and to characterize the latter as
an independent variant of GBS from clinical, laboratory,
and electrophysiological perspectives.
Methods
Patients and clinical data
Since 2007, the Dong-A University Neuroim-
munology Team (DAUNIT) has collected serum

© 2015 Peripheral Nerve Society 32

Kim et al. Journal of the Peripheral Nervous System 20:32–36 (2015)

from patients with suspected acute and chronic
immune-mediated neuropathies from more than 20
tertiary and university-based hospitals in Korea. The
main work of DAUNIT involves assessing the serum
anti-ganglioside antibody status. The clinical data of
these patients have also been registered by the on-site
researchers at each university. Both the results of the
anti-ganglioside assays and the clinical data remain
confidential.
This study reviewed the data of more than 900 con-
secutive patients from the aforementioned clinical and
DAUNIT anti-ganglioside antibody assay databases.
This patient dataset was searched for those with the
FD-predominant GBS variant. FDi was defined arbitrar-
ily as the isolated presentation of FD, and FDp as pres-
ence of FD coexisting with any of the following GBS
features: paresthesia of the distal limb, areflexia, A/C
dissociation, positive serum anti-ganglioside antibod-
ies, or minor NCS abnormalities.
To prevent confusion of this variant due to overlap
with classical GBS features, with the exception of distal
paresthesia, patients with FD accompanied by even
minor motor weakness or ataxia were excluded. This
approach meant that mild forms of classical GBS or
ataxic variants of GBS could be excluded. In addition,
patients for whom the etiology of FD was established
were also excluded.
The enrolled patients were analyzed and compared
based on their clinical, laboratory, and electrophysi-
ological findings. Detailed information on enrolled
patients was often obtained and corrected by their
charge doctor by additional questionnaires, telephone,
or direct personal contact if necessary. This study
was approved by the Ethics Committee of Dong-A
University Hospital.
Anti-ganglioside antibody assay
Serum samples were obtained from patients dur-
ing the acute stage within 2 weeks of symptom
onset. An enzyme-linked immunosorbent assay was
used to detect the various types of anti-ganglioside
antibodies, including immunoglobulin G (IgG), and
immunoglobulin M (IgM) antibodies against the gan-
gliosides GM1, GM2, GM3, GD1a, GD1b, GD3, GT1a,
GT1b, and GQ1b, as described previously (Kusunoki
et al., 1994; Kim et al., 2014). The presence and
types of anti-ganglioside antibodies were analyzed by
researchers who were blinded to the patients’ present-
ing neurological signs and electrophysiological classifi-
cations.
Results
The review of both the clinical data and
anti-ganglioside antibody status of 900 patients who
presented between January 2007 and December 2010
yielded eight patients with FDp. None of the patients
in the reviewed dataset satisfied the definition of
FDi. All enrolled patients with FDp shared the follow-
ing common features of GBS: monophasic course
and recovery, less than 4 weeks to clinical nadir, and
absence of retromastoid pain before the development
of facial palsy.
The clinical and laboratory findings of the FDp
cohort are summarized in Table 1. The mean age at
onset was 38 years (range: 9–72 years), and there
were five men and three women. FDp was accompa-
nied by more than one of the following GBS features:
subjective sensory symptoms such as paresthesia of
the distal limbs (7/8, 88%), A/C dissociation (7/8, 88%),
history of antecedent infection (6/8, 75%), and minor
NCS abnormalities (5/7, 71%). Only two patients pre-
sented with areflexia (2/8, 25%).
A facial NCS and blink-reflex test suggested the
presence of a bilateral facial nerve lesion in all the
tested patients. In a conventional NCS of the upper
and lower limbs, five of the seven patients exhibited
only mild changes of each parameter, most com-
monly a prolonged distal motor latency or slowing of
the sensory conduction velocity restricted to distal
compartments (Table 2). Interestingly, one patient

Table 1. Demographic and accompanying features of Guillain-Barré syndrome in eight patients with facial diplegia.
Other
Other CN sign or CSF
Age Antecedent subjective neurological protein IgM IgG IVIG Steroid
Case no. Sex (years) infection complaint sign (g/l) MP Ab MP Ab treatment treatment Prognosis

1 Female 31 Pharyngitis Tingling hands None 61 − − No Yes Good

2 Male 46 Pharyngitis Tingling hands Areflexic DTR 54 − − Yes No Good
3 Female 9 Pharyngitis Tingling limb None 83 + + No Yes Good
4 Male 51 Diarrhea Tingling limb Areflexic DTR 47 + ND Yes Yes Good
5 Female 27 None Tingling limb None 129.3 − − Yes No Good
6 Male 17 URI No None 51.3 − − No Yes Good
7 Male 32 None Tingling limb None 28.5 ND ND No Yes Good
8 Male 60 URI Tingling limb None 97 ND ND Yes Yes Poor

Ab, antibody; CN, cranial nerve; CSF, cerebrospinal fluid; DTR, deep tendon reflex; IgG, immunoglobulin G; IgM, immunoglobulin M; IVIG, intravenous
immunoglobulin; MP, mycoplasma; NCS, nerve conduction study; ND, not done; URI, upper respiratory tract infection.

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Kim et al. Journal of the Peripheral Nervous System 20:32–36 (2015)

Table 2. NCS findings of Guillain-Barré syndrome in seven patients with facial diplegia who undertook NCS within 1
week after symptom onset.

Facial NCS Blink reflex

Ipsilateral Ipsilateral Contralateral
TL (ms), CMAP (mV), R1 (ms), R/L R2 (ms), R/L R2 (ms), R/L Other NCS abnormalities
Case no. R/L (NL ≤ 3.0) R/L (NL ≥ 1.1) (NL ≤ 12.2) (NL ≤ 37.9) (NL ≤ 39.2) in limb NCS

1 1.6/1.6 1.9/1.9 NR/NR NR/47.0 45.6/48.1 Prolonged TL (median [B]),

low SNAP amplitude
(median [B], sural [R])
2 3.1/3.4 1.6/1.3 NR/NR NR/NR NR/NR Prolonged TL (median [R],
peroneal [R], posterior
tibial [R]), low SNAP
amplitude (median [R],
sural [R])
3 1.5/1.6 2.0/2.2 NR/NR NR/NR NR/NR Sensorimotor
demyelinating
polyneuropathy (Table
S1)
4 2.7/2.6 2.5/2.1 NR/NR NR/NR NR/NR None
5 3.0/3.1 1.5/1.6 NR/NR NR/NR NR/NR Prolonged TL (median [B],
ulnar [L], peroneal [B])
6 NR/NR NR/NR NR/NR NR/NR NR/NR None
8 2.9/2.9 1.6/2.0 NR/NR NR/NR NR/NR Prolonged TL (median [B],
ulnar [L], peroneal [B],
posterior tibial [B])

CMAP, compound muscle action potential; L, left; NL, normal limit; NR, no response; NCS, nerve conduction study; R, right; SNAP, sensory
nerve action potential; TL, terminal latency.

exhibited typical NCS features of demyelinating neu-
ropathy (Table S1, Supporting Information). The details
of this patient have previously been published in a case
report (Kim et al., 2007). The serum of all patients was
negative for anti-ganglioside antibodies to GM1, GM2,
GD1a, GD1b, GD3, GT1a, GT1b, and GQ1b; however,
two patients carried anti-mycoplasma antibodies (2/6,
33%).
Six of the eight patients (75%) were treated
with a course of oral steroids (60 mg prednisolone),
and a 5-day course of intravenous immunoglobulin
(IVIG) infusions (0.4 g/kg) was initiated in four patients
(50%). Seven patients exhibited a good prognosis, with
improvement of FD within 3 months. However, FD and
paresthesia persisted in one patient for more than
12 months from symptom onset.
Discussion
In this cohort, eight patients with FDp were identi-
fied who had more than one of the classical GBS find-
ings (e.g., postinfectious, monophasic, and nadir less
than 1 month). Therefore FD variant of GBS occurred in
less than 1% of patients registered at DAUNIT dataset.
The data suggest that FDp is a variant of GBS, espe-
cially when FD is accompanied by supporting features
of GBS. In addition, from an electrophysiological stand-
point, this variant appears to be a demyelinating neu-
ropathy.
GBS as a disease concept continues to evolve,
especially with respect to its wide clinical spectrum
of variants. Thus, while GBS was earlier defined as a
postinfectious dysimmunogenic peripheral neuropathy
of the arms and legs, it is now known that there are
variants of GBS that predominantly involve the cranial
nerves with or without the limb peripheral nerves. In
this context, “FD with distal paresthesia” in the new
classification system of GBS/Miller Fisher syndrome is
a representative regional variant (Wakerley et al., 2014).
This variant was first proposed by Ropper (1994) and
has since been characterized in more detail by Susuki
et al. (2009).
The cohort of Susuki et al. (2009) revealed that
all of the patients had A/C dissociation in the cere-
brospinal fluid, and in most of them demyelinating
abnormalities were detectable on NCSs. In terms of
clinical characterization, these findings have been con-
sistently reaffirmed by either this study or other case
reports (Barbi et al., 2011; Lehmann et al., 2012). There-
fore, this variant has been defined as one of the
clinical variants of GBS (Wakerley et al., 2014). How-
ever, from the pathophysiological perspective, some
issues remain to be determined: (1) Why does pares-
thesia of the distal limbs occur with FD? (2) Is the
molecular mimicry between certain microorganisms
also involved in the etiology of this variant? (Bae et al.,
2014).

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Kim et al.
Regarding the first dilemma, Susuki et al. (2009)
also suggested the concept of a “marginal case,”
defined as FD with no limb paresthesia or decreased
muscle stretch reflexes. One of the patients in this
study also exhibited no paresthesia but did have A/C
dissociation; this case may be a “marginal case”
according to the concept of Susuki et al. (2009). How-
ever, those authors provided no explanation for the
coexisting paresthesia in that FD variant. Indeed, the
same group previously reported “FD with hyperreflex-
ia” as a regional variant of GBS (Susuki et al., 2004),
but they concluded that this was a “marginal case” of
variant of FD with paresthesia (Susuki et al., 2009). This
suggestion is supported by a case report of a patient
who presented with FD accompanied by full-blown fea-
tures such as paresthesia and a brisk reflex (Lehmann
et al., 2012). One study suggested that areflexia helps
to distinguish between GBS as the underlying etiology
of FD (Sethi et al., 2007). However, only two of the
patients in this study (25%) exhibited areflexia; there-
fore, areflexia is not a useful finding in the diagnosis of
GBS for a patient exhibiting FD.
As to the second issue, in addition to
cytomegalovirus virus (Susuki et al., 2009), parvovirus
B19 (Barbi et al., 2011) and adenovirus (Lehmann et al.,
2012) have been suggested as candidate triggers of
this variant. Some of the patients in this study had
serological evidence of recent mycoplasma infec-
tion. Borrelia burgdorferi was frequently detected
in the cohort of Susuki et al. (2009); however, they
considered that a certain proportion of their positive
patients were in a subclinical carrier state rather than
having acute Lyme disease (Kaiser, 1998). In addi-
tion, they demonstrate the positivity of serum IgM
anti-ganglioside antibody to GM2. With the exception
of one case report of a patient with FDp who was pos-
itive for some anti-ganglioside antibodies, including
IgG GM2 (Vachalova et al., 2014), there have been no
other reports of positive anti-ganglioside antibodies in
this variant.
Whether or not relatively mild GBS and its variants
should be treated remains controversial. The appropri-
ate treatment for FDp has yet to be determined, but
the standard treatments for GBS seem to be reason-
able. In that sense, it is unclear whether or not FDp
variants need IVIG treatment. There is only one case
report supporting the usefulness of IVIG over steroid
treatment (Lehmann et al., 2012).
The findings of this study should be considered in
light of its limitations. One limiting factor pertains to
selection bias. The DAUNIT data analyzed in this study
was collected from tertiary medical centers, in which
only certain types of patient are likely to be enrolled.
The findings may thus not be generalizable to the
cases of FDi or FDp in general population. In addition,
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Journal of the Peripheral Nervous System 20:32–36 (2015)
the severity of the distinct features of FD relative
to the peripheral neuropathy in the limbs should be
considered. Patients with relatively mild FD might not
complain, and clinicians may overlook it if it is less
prominent due to its symmetry.
This findings suggest that FDp is a variant of GBS,
especially when the accompanying findings include
distal paresthesia and A/C dissociation. As an objec-
tive finding, minimal conventional NCS changes may
support a diagnosis of this syndrome. Neither history
of diarrhea nor areflexia were particularly helpful for
the identification of this syndrome. Although “FD with
paresthesia” is the most common characterization of
FDp, issues related to clinical and pathophysiological
uncertainty mean that this syndrome may be a het-
erogeneous group of syndromes rather than a single
clinical domain. The outcome of this variant appears
to be better than that of classical GBS; however, clin-
icians should pay careful attention as to whether this
syndrome can evolve into classical GBS with limb or
respiratory involvement.
Acknowledgements
This study was supported by grant no. 2014-14
from the Kangdong Sacred Heart Hospital Fund (J. S.
B.). J. K. K. designed the study. J. S. B., J. K. K., S. Y. O.,
E. H. S., Y. H. H., and S. M. J. conducted the data collec-
tion. J. S. B. and J. K. K. interpreted the data and wrote
this manuscript. All of the authors reviewed the first
manuscript draft, critically revised the manuscript, and
read and approved the final version. The funders played
no role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript
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