Acta Neurol Scand 2016: 133: 295301 DOI: 10.1111/ane.12459 2015 John Wiley & Sons A/S.

s A/S. Published by John Wiley & Sons Ltd

ACTA NEUROLOGICA
SCANDINAVICA

Hyponatraemia in GuillainBarre syndrome

revisited
Hiew FL, Winer JB, Rajabally YA. Hyponatraemia in GuillainBarre F. L. Hiew, J. B. Winer,
syndrome revisited. Y. A. Rajabally
Acta Neurol Scand 2016: 133: 295301. Regional Neuromuscular Clinic, Queen Elizabeth
2015 John Wiley & Sons A/SPublished by John Wiley & Sons Ltd. Hospital, University Hospitals of Birmingham,
Birmingham, UK
Objectives The objective of this study was to determine the relevance
of hyponatraemia in the prognosis of GuillainBarre syndrome
(GBS). Materials and methods We retrospectively analysed records
of 48 consecutive patients with GBS and performed a systematic
literature review on frequency/correlates of hyponatraemia in GBS.
Results Hyponatraemia <133 mmol/l was detected in 18/48 of our
patients with GBS (37.5%). In 10/18 (55.5%), hyponatraemia
occurred post-immunoglobulin therapy. Hyponatraemia correlated
with age >50 years (P = 0.011), concurrent malignancy (P = 0.039),
diuretic use (P < 0.001), preceding diarrhoea (P = 0.042) and Medical
Research Council (MRC) sum score at discharge (MRCSSD)
(P = 0.026). Only concurrent malignancy (P < 0.001) and diuretic use
(P < 0.001) were independently associated with hyponatraemia.
MRCSSD also correlated with MRC sum score on admission
(MRCSSA) (P < 0.001), length of hospital stay (P < 0.001),
summated compound muscle action potential (P = 0.034) and lowest
forced vital capacity (P = 0.001). Only MRCSSA (P = 0.004) and
length of hospital stay (P < 0.001) independently predicted MRCSSD.
Combining our findings with previous literature indicates comparable
frequencies of hyponatraemia in GBS in four of five studies and
Key words: critical illness; hyponatraemia; Guillain
association with mortality in three of four studies, with an Barre syndrome; neuropathy; outcome; prognosis;
independent link in one. Independent association of hyponatraemia sodium; syndrome of inappropriate secretion of
with muscle strength is not demonstrated. Conclusion antidiuretic hormone
Hyponatraemia appears of comparable frequency in GBS to that in Y. A. Rajabally, Regional Neuromuscular Clinic, Queen
other diseased cohorts suggesting it is common but non-specific. Elizabeth Hospital, University Hospitals of Birmingham,
Hyponatraemia has otherwise been shown to be an independent Birmingham B15 2TH, UK
predictor of death in other disorders and available data indicate the Tel.: +44 121 371 2000
same is also likely in GBS, although this may vary in patient e-mail: Yusuf.Rajabally@uhb.nhs.uk
subgroups. Hyponatraemia is, however, not an independent
prognostic indicator of neuromuscular weakness severity in GBS. Accepted for publication June 22, 2015

dysautonomia in GBS, resulting in sympathoad-

Introduction
The occurrence of hyponatraemia in Guillain
Barre syndrome (GBS) was initially described in
a few reports over 50 years ago (1, 2). Other than
the most widely suggested link to the syndrome
of inappropriate secretion of antidiuretic hor-
mone (SIADH) (3), the occurrence of hypona-
traemia in GBS has also been attributed to the
use of intravenous immunoglobulin (IVIg)
therapy (4). Another proposed mechanism has
been renal salt wasting syndrome as part of
renal dysregulation causing inappropriate brain
natriuretic peptide secretion and renal excretion
of sodium (5). The precise underlying aetiology
of hyponatraemia in GBS remains uncertain.
Multiple possible, often co-existing, causes are
likely. Various other postulated contributing fac-
tors to hyponatraemia in patients with GBS are
age, mechanical ventilation, fluid and electrolyte
imbalance as well as use of drugs (6).
Hyponatraemia has also been well documented
in critically as well as chronically ill subjects

295
Hiew et al.
unaffected by GBS. It is the most common and
important electrolyte disorder encountered in crit-
ical care units (7). Admission serum sodium levels
have been found useful together with plasma glu-
cose and white cell count, in predicting inpatient
mortality as well as mortality in community pop-
ulations with chronic conditions (8), while several
more recent studies have since highlighted the
independent value of hyponatraemia in predicting
mortality in various patient populations. In GBS,
hyponatraemia has been associated with disease
severity and death in few studies with indepen-
dent associations being mostly unconfirmed, par-
ticularly regarding muscle strength outcomes.
There are otherwise, to our knowledge, currently
no recent data on frequency and correlates of
hyponatraemia in patients with GBS from Eur-
ope or North America.
The objectives of our study was first to retro-
spectively determine the incidence and determi-
nants of hyponatraemia in GBS and secondly
ascertain the relationship with severity of muscle
weakness at hospital discharge, in our tertiary
UK. Neuromuscular centre over a 5-year period.
Other relevant intercorrelations were performed.
We also aimed to conduct a systematic review of
the literature regarding the frequency and signifi-
cance of hyponatraemia in GBS. Findings were
then analysed in the context of recent literature
on hyponatraemia in other conditions.
Materials and methods
We retrospectively reviewed our institutional data-
base of patients admitted with a diagnosis of GBS
between 2007 and 2012 (University Hospitals of
Birmingham, UK). The diagnosis was made in
each case in accordance with established clinical
criteria (5). Patients with Miller Fisher syndrome
(MFS), or incomplete MFS, as well as with
acute-onset chronic inflammatory demyelinating
polyneuropathy (CIDP), were excluded. MFS or
incomplete MFS was defined as the full or incom-
plete triad of ataxia, ophthalmoplegia and areflex-
ia, without associated limb weakness (9). Acute-
onset CIDP was defined by a characteristic clinical
picture of GBS with subsequent progression
beyond 9 weeks and/or with more than 3 episodes
of deterioration (5, 10). This work, which was part
of a larger retrospective analysis of clinical, biolog-
ical and electrophysiological features of GBS at
our institution, was a registered and approved ret-
rospective Clinical Audit by our relevant institu-
tional board (CAD-05169-13, University Hospitals
of Birmingham). Ethics committee approval was
not required.
296
We defined hyponatraemia as serum sodium
levels 133 mmol/l occurring at any time during
the first 3 weeks of inpatient stay. Patient demo-
graphics, total duration of inpatient stay, inten-
sive care admission and length of stay in
intensive care, Medical Research Council (MRC)
sum score at admission and discharge, were
ascertained. In addition, use of diuretics, concur-
rent malignancy, preceding diarrhoea, cranial
nerve and autonomic involvement, sepsis, use of
intravenous immunoglobulin (IVIg) pre-dating
hyponatraemia, presence of antiganglioside anti-
bodies and summated compound muscle action
potential were also determined.
Statistical analyses were performed using SPSS
22.0 software (SPSS Inc., Chicago, IL, USA).
Fisher exact tests were used for comparison of
proportions. Spearmans rank correlation with
2-tailed analysis was used to search for associa-
tions. We, in addition, performed, as appropriate,
multivariate logistic regression analyses to deter-
mine the eventual independent determinants of
hyponatraemia as well as of the primary outcome
of our study, predefined for the purposes of this
retrospective analysis, as the MRC sum score at
discharge, in our cohort. P values <0.05 were
considered as significant.
We also performed a systematic literature review
on hyponatraemia in GBS, as per the standard
guidelines for systematic literature reviews outlined
in the PRISMA statement (3). We conducted a
Medline search of all original articles published
between 1966 and February 2015 with the search
MeSH terms GuillainBarre syndrome, acute
inflammatory demyelinating polyradiculoneuropa-
thy, acute motor axonal neuropathy, acute
motor and sensory axonal neuropathy, acute
motor conduction block neuropathy, AIDP,
AMAN, AMSAN, AMCBN, hyponatraemia,
natraemia, sodium, syndrome of inappropriate
ADH secretion and SIADH. For meaningful
analysis of frequency and associations, we included
only articles describing series of at least 20
patients.
Results
We included 48 consecutive patients (32 males, 16
females) with a clinical diagnosis of GBS admit-
ted during the study period of 20072012. Mean
age was of 55.7 years (SD: 16.05). Mean length
of inpatient stay was 40.4 days (range 4217).
Concurrent malignancy was present in 5/48
(10.4%) patients, 5/48 (10.4%) were diabetic, and
15/48 (31.25%) were hypertensive. Nine patients
(18.75%) required mechanical ventilation.
 Hyponatraemia in GBS

Hyponatraemia was identified at any one

MRC Sum Score

at Discharge

r = 0.336;
P = 0.026
point during the first 3 weeks of inpatient stay

in 18/48 (37.5%) patients. In 10 cases, this was
mild (130133 mmol/l), and in 8, moderate/sev-
ere (<130 mmol/l). In 10/18 patients (55.5%),
hyponatraemia occurred after IVIg therapy.

r = 0.493; P = 0.001
Main findings of correlation analyses and logistic

Lowest FVC
regression are summarized in Tables 1 and 2.

NS
Significant correlations were ascertained between
hyponatraemia with age >50 years (Spearmans
rho: 0.363; P = 0.011), concurrent malignancy
(Spearmans rho: 0.299; P = 0.039), diuretic use

0.697; P < 0.001

Length of hospital stay
Table 1 Intercorrelation analyses of hyponatraemia and MRC sum score at discharge in 48 patients with GuillainBarre syndrome from Birmingham, UK, admitted between 2007 and 2012
(Spearmans rho: 0.488; P < 0.001), preceding
diarrhoea (Spearmans rho: 0.294; P = 0.042)
and Medical Research Council (MRC) sum

NS
score at discharge (MRCSSD) (Spearmans rho:

r=
0.336; P = 0.026). No correlations were found
between hyponatraemia and bulbar weakness,

0.32; P = 0.034
ophthalmoplegia, autonomic dysfunction, pres-

Summated CMAP
ence of antiganglioside antibodies or mechanical
ventilation. There was no significant correlation
with MRC sum score on admission (MRCSSA)

NS
(Spearmans rho: 0.19; P = 0.217). Significance

r=
was not reached for a correlation with facial
weakness (P = 0.072) or summated CMAP

MRC sum score

on admission

P < 0.001
r = 0.628;
(P = 0.113). Logistic regression showed that only

NS
concurrent malignancy (P < 0.001) and diuretic
use (P < 0.001) independently predicted hypona-
traemia. Excluding diuretic use from the analy-
sis, we found that age >50 years and malignancy r = 0.294; P = 0.042
Preceding diarrhoea

were the independent predictors of hypona-

traemia (P = 0.022 and P = 0.026, respectively).
MRCSSD correlated highly with MRCSSA
NS

(Spearmans rho: 0.628; P < 0.001). Correlations

of MRCSSD were otherwise ascertained with
hyponatraemia (Spearmans rho: 0.336;
P < 0.001
Diuretic use

r = 0.488;

P = 0.026), length of hospital stay (Spearmans

NS

rho: 0.697; P < 0.001), summated compound

muscle action potential (Spearmans rho: 0.32;
P = 0.034), lowest forced vital capacity (Spear-
Concurrent malignancy

r = 0.299; P < 0.001

mans rho: 0.493; P = 0.001), as well as mechanical

ventilation (Spearmans rho: 0.425; P = 0.004).
There were no correlations of MRCSSD with
NS

facial weakness, bulbar weakness or autonomic

dysfunction. Length of hospital stay (P < 0.001)
and MRCSSA (P = 0.004) were the only indepen-
0.336; P = 0.026
r = 0.363; P = 0.011

dent predictors of MRCSSD. There were 3 deaths

Age >50 years

overall (6.25%) during inpatient stay, occurring

at days 73, 176 and 217 days post-onset. There
was no correlation between hyponatremia and
death during inpatient stay (P = 0.881). Mortal-
r=

ity during inpatient stay correlated with concur-

rent malignancy (Spearmans rho=0.475;
MRC sum score
Hyponatraemia

at discharge

P = 0.001), intensive care admission (Spearmans

rho: 0.503; P < 0.001), mechanical ventilation
(Spearmans rho: 0.317; P = 0.028) and sepsis

297
Hiew et al.
Table 2 Logistic Regression analysis results of the independent associations of Hyponatraemia and MRC Sum Score at Discharge in 48 patients with GuillainBarre
syndrome from Birmingham, UK, admitted between 2007 and 2012
Hyponatraemia Age >50 years
Hyponatraemia NS
MRC sum score NS NA
at discharge
(Spearmans rho: 0.346; P = 0.016), but not with
age >50 years. Significance was approached for
correlations with MRCSSA (P = 0.061) and bul-
bar weakness (P = 0.065).
We retrieved from our systematic literature
review, a total of 4 articles which had descrip-
tions of incidence and correlates of hypona-
traemia in 20 patients with GBS (3, 6, 9, 10).
The reviewed articles are summarized in Table 3.
All four studies analysed frequency of hypona-
traemia in GBS. Three of those also evaluated
the correlates of hyponatraemia.
An initial descriptive study of management and
outcome of 79 UK patients with GBS found
25.3% had hyponatraemia (11). Somewhat
against the hypothesis of implication of mechani-
cal ventilation, this series had an unusually high
rate of respiratory involvement, of 73.4%.
The first large retrospective analysis dedicated
to the study of hyponatraemia in GBS, which
included in a total cohort of 84 subjects, patients
with MFS, was that from Christchurch, New
Zealand (6). This study described hyponatraemia
<133 mmol/l in 26/84 patients (31%). Hypona-
traemia was present prior to any therapeutic
intervention in 7/26 (26.9%, 12.5% of total
cohort) and was considered by the author to be,
in these patients, purely GBS related. However,
12/26 (46.1%) had experienced hyponatraemia
after treatment with IVIg, suggesting pseudohy-
ponatraemia as a frequent contributing factor. In
8 of those 12 patients, there was a well-docu-
mented progressive decrease in serum sodium
matching the IVIg infusion. In 7, the cause was
potentially multiple and complex with hypona-
traemia occurring in contexts of positive pressure
ventilation and/or plasmapheresis, multiple drug
therapy, jejunostomy, parenteral nutrition. Using
Fisher exact tests, the author described a signifi-
cantly greater number of deaths in hyponatraemic
patients (P = 0.001), although mortality was also
associated with age >50 years (P = 0.007) and
mechanical ventilation (P = 0.002). Timing of
death was not specified. The conclusion of this
study described strong inter-relationships between
these 3 factors, but independent effects were not
evaluated.
298
Preceding Concurrent Length of MRC sum score
diarrhoea malignancy Diuretic use hospital stay Summated CMAP Lowest FVC on admission
NS P < 0.001 P < 0.001 NA NA NA NA
NA NA NA P < 0.001 NS NS P = 0.004
There has been to date a single prospective
study of presence of hyponatraemia in GBS (3).
This study from Kerala, India, evaluated 50
patients with GBS and found that using a cut-off
of <135 mmol/l, 24 (48%) had SIADH. However,
only 18/50 (36%) had moderate or severe
hyponatraemia (<130 mmol/l). The authors used
chi-square and Students t-tests for statistical
analysis. Admission and discharge MRC sum
score were significantly poorer in hyponatraemic
subjects who had bulbar weakness and needed
mechanical ventilation significantly more fre-
quently. Subjects with SIADH had longer stays
in hospital and were deemed to need plasma
exchange more frequently. Age >50 years,
mechanical ventilation, bulbar weakness, but also
hyponatraemia, were said to be significantly asso-
ciated with mortality. Again, timing of death was
not specified. The Fisher exact test result compar-
ing mortality in the SIADH vs the non-SIADH
group, calculated from data provided in the
paper, gave a P value 0.045. Independent associa-
tions of any of these factors with muscle strength
at discharge or with mortality were not available.
The largest study to date is the latest published,
from northern China. This was a retrospective anal-
ysis published in Chinese (12). The authors studied
455 patients (283 males, 172 females) seen between
2003 and 2012, mean age 44.5 years, amongst
whom 61 (13.4%) had been mechanically ventilated,
and 322 (70.7%) treated with IVIg. A total of 98
patients (21.5%) had hyponatraemia <135 mmol/l.
Exclusion criteria described were varied and in some
cases insufficiently detailed including other neuro-
logical illness, poor oral intake, use of diuretics,
thyroid, adrenal, liver or kidney impairment,
paraneoplastic syndrome, past illness resulting in
weakness, difficult to differentiate from GBS, and
incomplete data or absence of tested sodium levels.
Number of exclusions for the latter reason was not
specified. Chi-square and logistic regression meth-
ods were used. Correlates of hyponatraemia were
age (P < 0.001), MRC sum score on admission
(P < 0.001), MRC sum score at nadir (P < 0.001),
facial weakness (P < 0.001), respiratory muscle
weakness (P < 0.001), bulbar weakness (P < 0.001)
and pneumonia (P < 0.001). Only age (P = 0.014),
 Hyponatraemia in GBS

facial weakness (P = 0.001) and mechanical ventila-

(2) Bulbar weakness

(3) Age >50 years
(1) Hyponatraemia
tion (P < 0.001) were found to be independently
Death
associated with hyponatraemia. Death, described as
in the acute stage but of unknown precise timing,
Independent associations

correlated with age >50 years (P = 0.006), MRC

sum score on admission (P = 0.011), hyponatremia
(P < 0.001), bulbar weakness (P < 0.001), pneumo-
(3) Mechanical ventilation

nia (P < 0.001) and facial weakness (P = 0.049).

Hyponatraemia

(2) Facial weakness

Death was surprisingly, however, not associated

Not ascertained

Not ascertained

Not applicable
mechanical ventilation (P = 0.992). Hyponatraemia
(1) Age >50

(P < 0.001) and bulbar weakness (P = 0.023) were

found to be independent predictors of death. Inde-
pendent predictors of MRC sum score at discharge
or a set time-point were not sought. Treatment was
(4) MRC score on admission

(2) Mechanical ventilation

(2) Mechanical ventilation

described as not correlating with hyponatraemia,

(2) Bulbar weakness

(4) Bulbar weakness

although timing of hyponatraemia in relation to

(6) Facial weakness
(1) Hyponatraemia

(3) Age >50 years

(3) Hyponatraemia

(3) Hyponatraemia
Death

IVIg administration was not studied.

(5) Pneumonia

(1) Age >50,

(1) Age >50,

Discussion
Correlations

Our study and literature review demonstrate the

(4) MRC score on admission

considerable heterogeneity of populations studied

(3) Mechanical ventilation

(2) Mechanical ventilation

(5) MRC score at nadir

and methodologies used including timing of as

(1) Bulbar weakness
(6) Bulbar weakness
(2) Facial weakness

well as cut-off values to define hyponatraemia

Hyponatraemia

itself. Cohorts were of different mean ages, with

(7) Pneumonia
(1) Age >50

Not studied
Table 3 Previous studies of hyponatraemia in GuillainBarre syndrome from systematic review of the literature 1966-February 2015

ours being older than others (55.7 vs 40.7 years

(1) Death

in the Indian series and 44.5 years in the Chinese

series; median of 46 years in the New Zealand
study). Our mean length of stay (40.4 days) was
Death (%)

4 (5.1)

significantly longer than in the Indian (calculated

18 (4)

4 (8)

6 (7)

at 14.47 days) and Chinese (7.38 days) cohorts.

Our patients were consecutive cases admitted to a
hyponatraemia, %

tertiary centre, some transferred from local gen-

Incidence of

eral hospitals, possibly implying greater severity,

21.5

25.3
48

31

more frequent presence of comorbidities or initial

diagnostic uncertainty. Exclusion criteria also dif-
fered in between studies. Timing of serum sodium
level measurement was equally problematic. We
Not Specified
of stay (days)
Mean length

considered levels during the first 3 weeks post-on-

7.38

14.47

33

set and considered arbitrarily any one abnormal

result. Previous studies failed to specify the tim-
ing altogether. This may be of importance as
46 years (1.585)
Mean Age (Range)

44.5 years (1584)

40.7 years (1570)

49.0 years (3268)

there may be different risks depending on

whether or not hyponatraemia preceded hospital
or intensive care unit admission (13). Whether a
more appropriate definition of hyponatraemia
would be to have at least 2 or more low-serum
levels is unknown. Our affected patients were for
Patients

455

50

84

79

the majority not further investigated for their

hyponatraemia, with infrequently measured uri-
nary sodium levels (14). This appears in keeping
Colls (6) (Retrospective)
Authors (Study design)

Saifudheen et al., (3)

with practice in the UK and may relate to the

Wang and Liu (12)

asymptomatic nature of the finding, and the per-

(Retrospective)

(Retrospective)
(Prospective)

Ng et al. (11)

ceived absence of effective therapies (14).

The findings of our current analysis highlight
the multiple determinants of hyponatraemia in

299
Hiew et al.
GBS. Iatrogenic causes are common as demon-
strated by the independent link with diuretic use
in our series. The post-IVIg pseudohypona-
traemias are related to a dilutional and usually
asymptomatic phenomenon (15). Excluding these,
our study and that of Colls (6), both demon-
strated a similar frequency of hyponatraemia
about 1 in 6. We found that hyponatraemia was
more common in older patients, in keeping with
data from all 3 other studies. We, like Colls (6),
but unlike Saifudheen et al. (3) and Wang and
Liu (12), failed to demonstrate an association of
hyponatraemia with mechanical ventilation. We,
on the other hand, not unexpectedly, found con-
current malignancy and diuretic use as indepen-
dent predictors of hyponatraemia. As regards
occurrence in context of known malignancy, our
patients importantly had typical GBS of demyeli-
nating or axonal subtypes, without associated
common antineuronal antibodies to indicate, con-
firming a paraneoplastic phenomenon. Interest-
ingly, we only found age to be an independent
predictor of hyponatraemia when we excluded
use of diuretics from the analysis, similar to
Wang and Liu (12). In a cohort with many exclu-
sions, including lack of adequate records, these
authors described, besides age, facial weakness
and mechanical ventilation as independently asso-
ciated with hyponatraemia (12). Although the
relationship with age and positive pressure venti-
lation may have a pathophysiological basis, the
independent link with facial weakness is more dif-
ficult to comprehend. Facial weakness is
described more commonly in post-CMV GBS
(16), although we are not aware of a link with
hyponatraemia in these cases.
We found, as in 2 of the other studies (3, 12),
a correlation of hyponatraemia with MRC score.
Timing of the MRC score, however, differed in
between studies. Interestingly, both of these
other two studies found that hyponatraemia cor-
related both with MRC sum score on admission
and at discharge or nadir. The former correla-
tion would importantly suggest greater disease
severity in hyponatraemic patients at onset,
rather than hyponatraemia itself altering the
neurological disease course and ultimately result-
ing in poorer functional outcome. We were our-
selves unable to find a correlation with
MRCSSA but found one with MRCSSD. As
also previously described by others, (17), we
ascertained an independent association between
MRCSSD and MRCSSA but not with hypona-
traemia. Independent associations of strength
and hyponatraemia were not confirmed by Wang
and Liu either (12).
300
There was no correlation of mortality with
hyponatraemia in our series. The reasons for this
may be multiple and, besides sample size, could
also include selection bias, and the study period
which was limited to inpatient stay within our
institution. Interestingly, one recent study of
patients with heart failure showed in a cohort of,
similarly of older subjects with more comorbidities,
that hyponatraemia did not predict mortality as to
opposed to in other patient groups (18), suggesting
these factors may influence the role of hypona-
traemia on outcome, at least in the short term.
Global results from all studies performed to date
in GBS, however, favour an association of hypona-
traemia with mortality, with an independent associ-
ation demonstrated by Wang and Liu (12).
Recent literature in relation to hyponatraemia
in other disorders is extensive. The largest retro-
spective study of >151,000 intensive care patients
showed a similar prevalence of hyponatraemia of
17.7% to that of most of the GBS studies and
demonstrated that it represented an independent
predictor of hospital mortality (19). A large
prospective point prevalence study of >13,000
participants also showed a comparable rate of
hyponatraemia in intensive care patients (12.9%),
confirming it as an independent predictor of mor-
tality (20). Hyponatraemia has also been recently
been found to be present in 16% of a large
cohort of >3000 patients with ischaemic stroke,
as well as represent a predictor of acute mortality
(21). Similarly, a large inpatient study of >50,000
patients has shown very frequent relative hypona-
traemia <138 mmol/l in admitted patients reach-
ing 38.2%, with again independent association
with mortality for community hyponatraemia and
hospital-acquired hyponatraemia (22). Likewise,
in a population-based cross-sectional U.S. study
of >14,000 subjects, hyponatraemia prevalence
was of 1.72% but it represented a predictor of
death independent of age, gender and comorbid
conditions (23).
These data demonstrate that hyponatraemia
occurs at fairly similar frequencies in different
hospitalized patients and is an independent pre-
dictor of death in all, including probably, asymp-
tomatic individuals. The limited data on GBS,
mainly due to its low incidence, are confirmatory
of comparable rates, between 16% and 25%,
excluding the non-IVIg induced, outlying higher
rate of 48% found in the Indian study. Hypona-
traemia similarly appears a mortality predictor in
GBS as shown in other disorders, in three of four
studies performed to date. The mechanisms impli-
cated in the higher mortality risk remain
unknown, and hyponatraemia may be a surrogate

marker for other unknown risk factors (24).
There is importantly no evidence of independent
implication of hyponatraemia on strength and
functional prognosis in GBS from studies per-
formed so far and the findings of the above-men-
tioned studies in other disorders also plead
against this.
In conclusion, although well described in recent
years and often in practice specially monitored in
patients with GBS, hyponatraemia appears a non-
specific, possible surrogate marker of underlying
disease severity (19), unrelated to GBS directly.
Discounting pseudohyponatraemia caused by
IVIg, it appears no more frequent in GBS than in
hospitalized patients with other acute or critical ill-
nesses. There is accumulating evidence that
hyponatraemia is a predictor of mortality in all
inpatients, including those with GBS. Whether this
is specific to certain GBS patient groups is
unknown and requires further study. The mecha-
nisms implicated are uncertain, but there may be
additive effects contributing to death. In GBS,
these may be in addition to underlying autonomic
dysfunction. There is, however, currently no evi-
dence for hyponatraemia as independent predictor
of neuromuscular prognosis in GBS as assessed by
motor strength.
Acknowledgements
We thank the Clinical Audit Office and Informatics at the
Queen Elizabeth Hospital, Birmingham, UK, for their help
with this work.
Conict of interests
None Declared in relation to this work.
Funding
None.
References
1. COOPER WC, GREEN IJ, WANG SP. Polyradiculopathy
(Guillain-Barre syndrome) with immunologic features
suggestive of neural hypersensitivity and with hypona-
tremia: report of a case. Rep U S Nav Med Res Lab
1963;15:17.
2. POYART C, POCIDALO JJ. Hyponatremia with natriuresis
conserved due to disorder of elimination of free water in
the course of Guillain-Barre syndrome. Rev Fr Etud Clin
Biol 1964;9:106871.
3. SAIFUDHEEN K, JOSE J, ABDUL GAFOOR V, MUSTHAFA M.
Guillain-Barre syndrome and SIADH. Neurology
2011;76:7014.
4. KOFFMAN BM, DALAKAS MC. Effect of high-dose intra-
venous immunoglobulin on serum chemistry, hematology
and lymphocyte subpopulations: assessments based on
Hyponatraemia in GBS
controlled treatment trials in patients with neurological
diseases. Muscle Nerve 1997;20:11027.
5. LENHARD T, GRIMM C, RINGLEB PA. Renal salt wasting
as part of dysautonomia in Guillain-Barre syndrome. J
Neurol Neurosurg Psychiatry 2011;82:10513.
6. COLLS BM. Guillain-Barre syndrome and hyponatraemia.
Intern Med J 2003;33:59.
7. PATEL GP, BAULK RA. Recognition and treatment of
hyponatremia in acutely ill hospitalized patients. Clin
Ther 2007;29:21129.
8. ASSADOLAHI K, HASTINGS IM, BEECHING NJ, GILL GV.
Laboratory risk factors for hospital mortality in acutely
admitted patients. QJM 2007;100:5017.
9. WAKERLEY BR, UNCINI A, YUKI N, GBS Classification
Group, GBS Classification Group. Guillain-Barre and
Miller Fisher syndromesnew diagnostic classification.
Nat Rev Neurol 2014;10:53744.
10. RUTS L, DRENTHEN J, JACOBS BC, VAN DOORN PA, Dutch
GBS Study Group. Distinguishing acute-onset CIDP
from fluctuating Guillain-Barre syndrome: a prospective
study. Neurology 2010;74:16806.
11. NG KK, HOWARD RS, FISH DR et al. Management and
outcome of severe Guillain-Barre syndrome. QJM
1995;88:24350.
12. WANG Y, LIU J. The relationship between hyponatraemia
and the prognosis of Guillain-Barre syndrome. Chin J
Neurol 2013;9:597600.
13. SAKR Y, ROTHER S, FERREIRA AM et al. Fluctuations in
serum sodium level are associated with an increased risk
of death in surgical ICU patients. Crit Care Med
2013;41:13342.
14. TZOULIS P, EVANS R, FALINSKA A et al. Multicentre study
of investigation and management of inpatient hypona-
traemia in the UK. Postgrad Med J 2014;90:6948.
15. STIEHM ER. Adverse effects of human immunoglobulin
therapy. Transfus Med Rev 2013;27:1718.
16. ORLIKOWSKI D, PORCHER R, SIVADON-TARDY V et al.
Guillain-Barre syndrome following primary cytomegalo-
virus infection: a prospective cohort study. Clin Infect
Dis 2011;52:83744.
17. WALGAARD C, LINGSMA HF, RUTS L, VAN DOORN PA,
STEYERBERG EW, JACOBS BC. Early recognition of poor
prognosis in Guillain-Barre syndrome. Neurology
2011;76:96875.
18. 
LORIDO JC, GOMEZ JC, FORMIGA F et al. Hyponatremia
as predictor of worse outcome in real world patients
admitted with acute heart failure. Cardiol J 2013;20:506
12.
19. FUNK GC, LINDNER G, DRUML W et al. Incidence and
prognosis of dysnatremias present on ICU admission. In-
tensive Care Med 2010;36:30411.
20. VANDERGHEYNST F, SAKR Y, FELLEITER P et al. Incidence
and prognosis of dysnatraemia in critically ill patients:
analysis of a large prevalence study. Eur J Clin Invest
2013;43:93348.
21. RODRIGUES B, STAFF I, FORTUNATO G, MCCULLOUGH LD.
Hyponatremia in the prognosis of acute ischemic stroke.
J Stroke Cerebrovasc Dis 2014;5:8504.
22. WALD R, JABER BL, PRICE LL, UPADHYAY A, MADIAS
NE. Impact of hospital-associated hyponatremia on
selected outcomes. Arch Intern Med 2010;170:294302.
23. MOHAN S, GU S, PARIKH A, RADHAKRISHNAN J. Preva-
lence of hyponatremia and association with mortality:
results from NHANES. Am J Med 2013;126:112737.
24. HOORN EJ, ZIETSE R. Hyponatremia and mortality: mov-
ing beyond associations. Am J Kidney Dis 2013;62:139
49.
301