Pediatr Nephrol
DOI 10.1007/s00467-014-2799-2
BRIEF REPORT
Bladder dysfunction and hypertension in children
with Guillain–Barre syndrome
Louise Watson & Majid Aziz & Grace Vassallo &
Nicholas D. Plant & Nicholas J. A. Webb
Received: 17 December 2013 / Revised: 23 February 2014 / Accepted: 25 February 2014
# IPNA 2014
Abstract
Background Guillain–Barre syndrome (GBS) causes acute
motor, sensory and autonomic dysfunction. There is a relative
paucity of published data regarding the autonomic features of
GBS. The aims of this study were to describe the incidence,
management and outcome of bladder dysfunction and hyper-
tension in GBS and to ascertain whether these features relate
to muscle weakness severity.
Case-Diagnosis/Treatment Twenty-seven patients with a me-
dian (interquartile range) age of 5.7 (3.5–8.4) years were
included, of whom 18 (67 %) were male and 14 (52 %) had
autonomic dysfunction. One patient presented with and three
subsequently developed urinary retention necessitating cathe-
terisation for a median of 7.5 (7–14.5) days. Univariate anal-
ysis demonstrated that urinary retention was associated with
weakness in all four limbs [retention: MRC muscle grade 2
(2–2.75); no retention: MRC grade 4 (3–4); p=0.02], possibly
reflecting more severe disease. Patients with hypertension (12
patients, 44 %) had a longer hospital stay [median 32.5
(15.5–53.5) days; rho = 0.65; p=0.02], and those with worse
muscle weakness required more anti-hypertensive medica-
tions (upper limb rho = −0.71, p=0.03; lower limb rho =
L. Watson : N. D. Plant : N. J. A. Webb
Department of Paediatric Nephrology, Royal Manchester Children’s
Hospital and Manchester Academic Health Science Centre,
University of Manchester, Manchester, UK
M. Aziz : G. Vassallo
Department of Paediatric Neurology, Royal Manchester Children’s
Hospital, Manchester, UK
L. Watson (*)
Department of Paediatric Nephrology, Royal Manchester Children’s
Hospital, Oxford Road, Manchester, UK M13 9WL
e-mail: louise.watson@liv.ac.uk
−0.72, p=0.03]. The majority of blood pressure treatments
involved calcium channel and beta blockers.
Conclusion In children with GBS, bladder dysfunction and
hypertension are common. The presence of severe muscle
weakness may predict those at greatest risk of these
complications.
Keywords Guillain–Barre syndrome . Hypertension . Child .
Autonomic dysfunction
Introduction
Guillain-Barre syndrome (GBS) is an acute inflammatory
poly-neuropathy causing motor, sensory and autonomic dys-
function. The clinical presentation is a symmetrical ascending
paralysis that peaks in less than 4 weeks, together with pain
and paraesthesia that is followed by a plateau phase and then a
slow recovery. The degree of motor weakness, sensory in-
volvement and dysautonomia varies, and disease progression
can be rapid [1]. It is rare in children, with an estimated
incidence of 0.6 cases per 100,000 children [2], and clinical
outcome data from large paedriatic patient cohorts are there-
fore lacking. In about 60 % of patients GBS is believed to
occur due to anti-ganglioside antibodies, often triggered by
infectious pathogens through molecular mimicry [3]. Auto-
nomic dysregulation is common [4], frequently including
bladder instability and labile blood pressure that may require
input from a paediatric nephrologist. Previous studies in child-
hood GBS have reported hypertension in up to 69 % of cases,
and it has been proposed that this may be linked to the severity
of the muscle weakness [4].
The aim of this study was to describe the incidence, man-
agement and outcome of bladder dysfunction and hypertension

in a large cohort of children with GBS and to ascertain whether
these features relate to the severity of muscle weakness.
Methods
This study was a retrospective review of patients admitted to
the Royal Manchester Children’s Hospital, a large tertiary
paediatric centre, between January 2002 and December
2012. Cases were identified through a review of the hospital
records system using the International Classification of Dis-
ease code.
Patient data included basic demographic details, presenting
symptoms and features of autonomic dysfunction (tempera-
ture instability, significant blood pressure changes, heart rate
variability, sweating, ileus, presence of urine retention and
incontinence) that developed during the course of admission.
The presence of bladder dysfunction and its management
(need for and duration of insertion of urethral catheter) was
recorded. Disease activity was measured in terms of maxi-
mum upper limb (UL) [5] and lower limb (LL) motor weak-
ness using the Medical Research Council (MRC) muscle
strength grading system [6].
The MRC grades are:
& 5—normal power;
& 4—active movement against gravity with resistance;
& 3—active movement against gravity without resistance;
& 2—active movement with gravity eliminated;
& 1—trace or flicker of movement;
& 0—no movement.
The incidence and management of hypertension, the length
of stay in the hospital and admission to the paediatric intensive
care unit (PICU) were also documented. Outcomes were
measured at 6-months post-presentation.
The diagnosis of GBS was made by a paediatric neurologist
based on a combination of clinical history, examination, in-
creased cerebrospinal fluid protein concentrations and nerve
conduction studies (NCS), together with the exclusion of other
conditions through brain and spinal cord imaging. Clinical and
NCS features defined GBS subtypes into acute inflammatory
demyelinating polyradiculoneuropathy (AIDP), acute motor
axonal neuropathy (AMAN), acute motor and sensory axonal
neuropathy (AMSAN) and Miller–Fisher syndrome (MFS).
Hypertension was defined as a persistent systolic blood
pressure (SBP) measurement of >95th centile for the child’s
age, sex and height measured on at least three occasions [7].
Hypertension was defined as being controlled when the anti-
hypertensive medications administered resulted in a SBP of
<95th centile and as resolved when the SBP fell to <95th
centile without recourse to antihypertensive medication.
Pediatr Nephrol
Statistical analysis was performed using the Statistics Pack-
age for Social Sciences (SPSS ver. 20; IBM Corp Ltd,
Armonk, NY), and the data were described using the median
and interquartile range (IQR). Spearman rho correlation coef-
ficient was denoted as ‘rho’. Statistical probability (p) values
of <0.05 were considered significant. This study was a retro-
spective clinical review and, therefore, ethical approval was
not required.
Results
Thirty patients with a diagnosis of GBS presenting between
January 2002 and December 2012 were identified through our
hospital coding system. Three patients were excluded: two
had a diagnosis other than GBS [POEMS (polyneuropathy,
organomegaly, endocrinopathy, M protein, and skin changes)
syndrome and epilepsy, respectively] and for one patient the
case notes were unobtainable although hospital records indi-
cated that the patient was alive and no longer under specialist
follow-up. Therefore, 27 patients with a confirmed diagnosis
of GBS were included in our analysis. A description of the
demographic details and the presenting disease features is
given in Table 1.
All patients presented with ascending flaccid paresis and
areflexia (100 %), three patients (11 %) had respiratory depres-
sion (including one with respiratory arrest), ten patients (37 %)
had bulbar involvement, two patients (8 %) had
ophthalmoplegia, 16 patients (59 %) had limb pain, ten patients
(37 %) had ataxia and three patients (11 %) presented with hip
pain. Only 13 patients (48 %) in our cohort had NCS per-
formed. Clinical and neurophysiological subtypes of GBS
identified were AIDP (n=3), AMAN (n=2), AMSAN (n=6)
and MFS (n=2). Twenty-two (81 %) patients received intrave-
nous immunoglobulin (IVIG) at 2 g/kg dose within 48 h of
diagnosis. Three patients (14 %) received a repeat dose of IVIG
and one received rituximab due to clinical deterioration and
persistent Epstein–Barr virus infection with subsequent im-
provement. No patient received plasma exchange therapy. Ad-
verse effects associated with IVIG administration (blood pres-
sure changes, tachycardia) were not observed in our cohort.
Autonomic dysfunction developed in 14 patients (52 %).
The median time from the onset of muscle weakness to the
development of any form of autonomic dysfunction was 7.5
(IQR 3–9.3) days. On average, autonomic dysfunction had its
onset at the same time as the disease activity reached its plateau
phase of maximal weakness (interval = 0 days, IQR 0–1.3).
Seven patients (26 %) already had bladder or bowel sphinc-
ter disturbance at the time of presentation: five with urinary
incontinence, one with urinary retention and one with consti-
pation. These were all preceded by the symptoms of muscle
weakness. An additional three patients developed urinary
retention during their admission. A total of six patients
Pediatr Nephrol

Table 1 The demographic, presentation and disease activity features seen Hypertension was the most common manifestation of au-
in a cohort of children with Guillain–Barre syndrome (n=27 patients)
tonomic dysfunction and was seen in 12 patients (44 %), at a
Cohort characteristics median of 5 (IQR 2–10) days after the initial onset of muscle
weakness. Hypertension lasted for a median of 11 (IQR 7–26)
Feature Number (IQR or %) days until resolution or control and was statistically signifi-
Age 5.7 (3.5–8.4) years
cantly correlated with the length of hospital stay (rho=0.65,
p=0.02). No patient developed hypertensive encephalopathy.
Male sex 18 (67 %) patients
Nine patients required anti-hypertensive treatment (33 % of
Ethnicity
the total cohort or 75 % of those with hypertension) for a
Caucasian 14 (52 %) patients
median of 22 (IQR 3–39) days. The number of anti-
Asian 11 (41 %) patients
hypertensive medications required correlated significantly
Afro-Caribbean 1 (3.5 %) patients
with the extent of muscle weakness in both the upper and
Missing data 1 (3.5 %) patients
lower limbs (UL MRC grade rho = −0.71, p=0.03; LL MRC
Presentation to confirmed diagnosis 2 (1–5) days
grade rho = −0.72, p=0.03). Table 2 provides information on
Symptom onset to maximum weakness 6 (4–8) days
the precise treatment used for the management of hyperten-
LP performed 22 (81 %) patients
sion in this cohort. Neuropathic pain associated with GBS
Duration of symptoms to LP 8 (4–16.5) days
was managed with analgesia, consisting of opioids in
Cerebrospinal fluid protein concentration 1.04 (0.60–1.97) g/L
eight (29 %) patients, gabapentin in 17 (62 %) patients,
(normal range 0.15–0.6 g/L)
Plateau phase 7 (5–13) days pregabalin in two (7 %) patients and amitriptyline in
Maximum upper limb weakness 3 (3–4) MRC grade one (3 %) patient. There was no correlation between the
Maximum lower limb weakness 2 (2–3) MRC grade presence of persistent hypertension and the severity of
Autonomic dysfunction 14 (52 %) patients neuropathic pain or the number of medicines used to
Onset weakness to autonomic dysfunction 7.5 (3–9.3) days control parasthesia.
Plateau phase to autonomic dysfunction 0 (0–1.3) days Only five patients with hypertension (5/12; 42 %) had
Admission to paediatric intensive care unit 6 (22 %) patients further investigations performed, including renal ultrasound
Immunoglobulin use 22 (81 %) patients
(n=5, all were normal), urine catecholamines (n=1, increased
Steroid use, rituximab use 1 (4 %) patient, 1
catecholamine excretion reported), echocardiography to as-
(4 %) patient sess left ventricular hypertrophy (LVH) (n=3; 1 patient
Neuropathic pain relief 19 (70 %) patients with no LVH, and two patients with LVH that resolved
Gabapentin 17 patients in both on follow-up).
Pregabalin 1 patient
Amitriptyline 1 patient Table 2 The number of patients who experienced hypertension in a
Length of hospital stay 32.5 (15.5–53.5) days cohort of children with Guillain–Barre syndrome (n=27 patients) and
its onset in relation to other symptoms together with the choice of anti-
LP, Lumbar puncture; IQR, interquartile range; MRC, Medical Research hypertensive medications used
Council
Type of medicine Number

Presence of hypertension 12 patients (44 % of

cohort)
ultimately required urethral catheterisation, including one pa-
Duration of hypertension 11 (IQR 7.3–26) days
tient with urinary retention at presentation, three patients who
Time between symptoms to hypertension 5 (IQR 2–9.5) days
developed retention during admission and two patients with
no clinical features of bladder involvement who were cathe- Need for antihypertensive medication 9 patients (33 % of
cohort)
terised whilst sedated on the PICU. The median duration of
Duration of antihypertension treatment 21.5 (IQR 2.8–39) days
catheter insertion was 7.5 (IQR 7–14.5) days with no docu-
Type of anti-hypertensive medication (n patients)
mented complications. The development of urinary retention
Nifedipine 2
(either at presentation or during admission) correlated signif-
Amlodipine 1
icantly with involvement of all four limbs and the severity of
Atenolol 2
UL weakness [presence of urinary retention maximum UL
Propanolol then amlodipine 1
MRC score 2 (IQR 2–2.75); no retention score 4 (3–4);
Amlodipine, Atenolol 1
p=0.02), and this trend was also seen with increased LL
Sodium nitropruside, amlodipine, 1
weakness, although not statistically significant [urinary reten-
propanolol
tion maximum LL MRC score 2 (IQR 1–3); no retention score Amlodipine, Atenolol, Amiloride 1
3 (IQR 2–3); p=0.15].

At 6-months after the acute presentation 15 patients (56 %)
had normal muscle strength. Two patients who were continent
prior to diagnosis had ongoing incontinence (one had urinary
incontinence with nocturnal enuresis and daytime dribbling,
one patient had faecal incontinence), and both had muscle
weakness that was still recovering. All patients had stopped
anti-hypertensive treatment and had normal casual blood pres-
sure readings.
Discussion
Childhood GBS is an acute-onset, monophasic, immune-
mediated polyneuropathy that has a high tendency for
dysautonomic features. The aim of our study was to describe
the incidence of bladder dysfunction and hypertension in
childhood GBS using an 11-year cohort. Similar to findings
reported in other studies, we have demonstrated that this
condition has a male preponderance and in this paediatric
cohort manifested at around 5 years of age. Our cohort had
an unexpectedly large proportion of children of South Asian
origin (41 % of our cohort) when compared to the proportion
of South Asian individuals in the local population (6.5 %),
suggesting a possible influence of ethnicity on disease sus-
ceptibility, as previously suggested by others [8, 9]. The
plateau phase of maximum disability in our patient cohort
lasted for 7 days, in keeping with that described previously
[10], and we have shown that the plateau phase is when
patients are at highest risk of developing autonomic features.
We have demonstrated that bladder dysfunction is relative-
ly common in childhood GBS. Univariate analysis revealed
that the presence of urinary retention (seen in 15 % of the
cohort) was associated with paralysis ascending to involve all
four limbs and the degree of upper limb weakness. Bladder
dysfunction is well recognised in adult patients with GBS. In a
cohort of 38 adults, urodynamic abnormalities were shown to
be associated with worse overall disability scores [11], in
concordance with our findings in children and those reported
by others [4, 12].
Hypertension was commonly detected (44 %) in our co-
hort, and the majority of children required treatment. Univar-
iate statistical analysis revealed that hypertension was more
difficult to control in our patients with the worst muscle
weakness. Additionally, we found that the duration of hyper-
tension correlated with the overall length of hospital stay, a
finding also noted recently by other authors [4]. Our study is
the largest to date to report the specific management of hy-
pertension in this condition; the choice of anti-hypertensive
treatment used was variable, with most patients treated with
beta or calcium channel blockers as first-line therapy; these
agents were also used in a number of single case reports
published in the literature [4, 13–15]. Relatively few patients
in our cohort had investigations performed for hypertension.
Pediatr Nephrol
The published literature suggests that these are unlikely to be
helpful as increased catecholamine secretion is usually tem-
porary and reversible LVH is known to occur [16, 17]. Reas-
suringly, hypertension and LVH had completely resolved in
all of our patients at follow-up.
Despite the common finding of autonomic dysfunction in
GBS, there is no consensus regarding its management, includ-
ing that of hypertension. Interestingly, the Cochrane review of
the neurological features of GBS noted a statistically signifi-
cant reduction in the incidence of hypertension in patients
treated with corticosteroids, and this is an area that may
warrant further investigation [18].
Limitations of this study include its retrospective nature,
meaning that confounding factors, such as pain, may have
influenced our findings, together with its relatively small size.
Multivariate analysis using a larger sample size with prospec-
tive, standardised BP evaluation and formal bladder assess-
ment is required to assess any independent associations be-
tween bladder dysfunction, hypertension and disease activity
which may corroborate our findings. However, our study
delivers two clear messages. Firstly, that hypertension and
bladder involvement is common, easily managed and typical-
ly transient and secondly that extensive investigations are not
required unless patients have an atypical disease course. Our
findings provide the paediatric nephrologist with information
on the natural history for children with GBS and provide
preliminary evidence that patients with more severe muscle
weakness, especially disease ascending to involve the upper
limbs, are at the greatest risk of elevated blood pressure and
bladder dysfunction.
Conclusion
Bladder dysfunction and hypertension are commonly encoun-
tered in GBS at the time of maximal weakness. Patients with
more severe muscle weakness seem to be at the greatest risk of
developing these complications.
References
1. Hicks CW, Kay B, Worley SE, Moodley M (2010) A clinical picture
of Guillain-Barre syndrome in children in the United States. J Child
Neurol 25:1504–1510
2. Rantala H, Cherry JD, Shields WD, Uhari M (1994) Epidemiology of
Guillain-Barre syndrome in children: relationship of oral polio vac-
cine administration to occurrence. J Pediatr 124:220–223
3. Yu RK, Usuki S, Ariga T (2006) Ganglioside molecular mimicry and
its pathological roles in Guillain-Barre syndrome and related dis-
eases. Infect Immun 74:6517–6527
4. Dimario FJ Jr, Edwards C (2012) Autonomic dysfunction in child-
hood Guillain-Barre syndrome. J Child Neurol 27:581–586
Pediatr Nephrol
5. Sadovnick AD, Paty DW, Yannakoulias G (1989) Concurrence of
multiple sclerosis and inflammatory bowel disease. N Engl J Med
321:762–763
6. Compston A (2010) Aids to the investigation of peripheral nerve
injuries. Medical Research Council: Nerve Injuries Research
Committee. His Majesty’s Stationery Office: 1942; pp. 48 (iii) and
74 figures and 7 diagrams; with aids to the examination of the
peripheral nervous system. By Michael O’Brien for the Guarantors
of Brain. Saunders Elsevier: 2010; pp. [8] 64 and 94 Figures. Brain
133:2838–2844
7. National High Blood Pressure Education Program Working Group
on High Blood Pressure in Children and Adolescents (2004) The
fourth report on the diagnosis, evaluation, and treatment of high
blood pressure in children and adolescents. Pediatrics 114[2 Suppl
4th Report]:555–576
8. McKhann GM, Cornblath DR, Griffin JW, Ho TW, Li CY, Jiang Z,
Wu HS, Zhaori G, Liu Y, Jou LP, Liu TC, Gao CY, Mao JY, Blasser
MJ, Misu B, Asbury AK (1993) Acute motor axonal neurop-
athy: a frequent cause of acute flaccid paralysis in China. Ann
Neurol 44(4):333–342
9. Ogawara K, Kuwabara S, Mori M, Hattori T, Koga M, Yuki N (2000)
Axonal Guillain-Barre syndrome: relation to anti-ganglioside anti-
bodies and Campylobacter jejuni infection in Japan. Ann Neurol
48(4):624–631
10. Linden V, Da Paz JA, Casella EB, Marques-Dias MJ (2010) Guillain-
Barre syndrome in children: clinic, laboratorial and epidemiologic
study of 61 patients. Arq Neuropsiquiatr 68:12–17
11. Naphade PU, Verma R, Garg RK, Singh M, Malhotra HS, Shankwar
SN (2012) Prevalence of bladder dysfunction, urodynamic findings,
and their correlation with outcome in Guillain-Barre syndrome.
Neurourol Urodyn 31:1135–1140
12. Cooper WO, Daniels SR, Loggie JM (1998) Prevalence and corre-
lates of blood pressure elevation in children with Guillain-Barre
syndrome. Clin Pediatr (Phila) 37:621–624
13. Smith N, Grattan-Smith P, Andrews IP, Kainer G (2010) Acquired
facial palsy with hypertension secondary to Guillain-Barre syndrome.
J Paediatr Child Health 46:125–127
14. Labovitz AE, Mangurten HH (2004) Guillain-Barre syndrome pre-
senting with urinary retention and hypertension. Clin Pediatr (Phila)
43:659–661
15. Abend NS, Bonnemann CG, Licht DJ (2007) Status epilepticus
secondary to hypertensive encephalopathy as the presenting mani-
festation of Guillain-Barre syndrome. Pediatr Emerg Care 23:659–
661
16. Ahmad J, Kham AS, Siddiqui MA (1985) Estimation of plasma and
urinary catecholamines in Guillain-Barre syndrome. Jpn J Med 24:
24–29
17. Iga K, Himura Y, Izumi C, Miyamoto T, Kijima K, Gen H, Konishi T
(1995) Reversible left ventricular dysfunction associated with
Guillain-Barre syndrome—an expression of catecholamine
cardiotoxicity? Jpn Circ J 59:236–240
18. Hughes RA, Swan AV, van Doorn PA (2010) Corticosteroids
for Guillain–Barre syndrome. Cochrane Database Syst Rev 2:
CD001446