Clinical Short Term Outcome of GuillainBarré Syndrome in ...Document Transcript
Iran J Pediatr
Mar 2008; Vol 18 ( No 1), Pp:11-19
Clinical Short Term Outcome of GuillainBarré
Syndrome in Children
Mahmoud Reza Ashrafi1, MD, Pediatric Neurologist; Setareh Sagheb 1, MD; Pediatrician;
Mahmood Mohammadi1, MD, Pediatric Neurologist; Anoushiravan Vakili, MD, Geneal Physician;
Abolfazl Nasirian1, MD, Neurologist; Gholam Reza Zamani1, MD, Pediatric Neurologist
1. Department of Pediatrics, Medical Sciences/University of Tehran, Iran
Received: 14/08/07; Revised: 01/11/07; Accepted: 04/12/07
Objective: Several factors are useful in predicting the prognosis of Guillain‐Barre syndrome
(GBS). The objective of this study was to determine the role of clinical presentation scaling to
predict patient's short‐term outcome.
Material & Methods: Forty five patients with the confirmed diagnosis of GBS, according to
international diagnostic criteria, were enrolled in this study. All children who were not able to
walk unaided (i.e., ordinal disability score=ODS ≥3) were treated with intravenous
immunoglobulin (IVIg) alone or with corticosteroid. The primary outcome measures were the
degree of disability at discharge, length of hospital stay, need to intensive care setting and
Findings: Male to female ratio was 1.05: 1 with mean age of 5.9 years. The most common
manifestation was limb weakness (71.1%). Absent or decreased deep tendon reflexes were
seen in 44% and 53.3% patients, respectively. All children experienced some degree of pain,
with moderate to severe intensity (pain faces score ≥3) in 91.2% patients. Cranial nerve
involvement was found in 46.7% children, most commonly as bulbar weakness (40%). Ten
(22.2%) patients were admitted in PICU, and ventilation support was needed for 2 (4.4%) of
them. Clinical response was regain of unaided walking (ODS≤2) which was achieved in 62.2%
patients. After treatment all patients developed significant improvement of functional disability
which was assessed by ODS and arm function scores. A higher ODS at presentation was
associated significantly with a longer hospital stay (P=0.03) and higher arm function score
(P<0.001). Absent tendon reflexes and cranial nerve involvement were associated with higher
functional scores, longer hospital stay and admission in PICU. Also, higher arm function scores
were associated significantly with intensive care unit admission (P=0.01).
Conclusion: These results indicate that the ODS and arm function scores can be applied as
prognostic factor for clinical short‐term outcome among GBS patients.
Key Words: Guillain‐Barré syndrome; Childhood; ODS; Functional disability; Arm Function
score; Pain scale
* Correspondence author;
Address: Division of Pediatric Neurology, Children’s Medical Center, 62 Gharib St, 14194 Tehran, IR Iran
12 Outcome of GuillainBarre Syndrome in Children. MR Ashrafi, et al
Introduction ability of patients at presentation or during
the study and its comparison after treatment
Guillain‐Barré syndrome (GBS) is an acute has been investigated frequently to assess the
immune‐mediated polyradiculoneuropathy role of different treatments. These tests
characterized by symmetric ascending were rarely used as a prognostic factor to
weakness and spontaneous remission[1,2].It is predict the patient’s functional outcome, need
the most common cause of acute flaccid for ICU admission or length of hospital stay.
paralysis in children which often leads to Moreover, there are limited epidemiological
respiratory and bulbar compromise[3,4]. The data reported in Asian populations about
incidence of the disease has been previously GBS[13,16,17].
reported to be between 0.4 to 0.6 / 100,000 in In this study, we prospectively evaluated
western countries and 1.5 to 3.4 / 100,000 in the clinical outcome of children with different
Iran[5,6]. subtypes of GBS and their functional outcome
Based on clinical features and electro‐ based on Ordinal Disability Scale (ODS), Arm
diagnotic criteria GBS can be sub classified Function score and Pain Faces Scale (Smiley
into heterogeneous groups of syndromes such Scale) to identify prognostic indicators along
as acute inflammatory demyelinating with cerebro‐spinal fluid (CSF) findings and
polyradiculo‐neuropathy (AIDP), acute motor electrophysiological investigations.
axonal neuropathy (AMAN), acute motor‐
sensory axonal neuropathy (AMSAN) and
Miller‐Fisher syndrome (MFS). In European
and US studies the AIDP is the most prevalent Material & Methods
form with an incidence between 85% to 90%
of cases with GBS in spite of Asian studies After obtaining approval from the Institutional
which report it about 53%[6‐9]. In 70–80 % of Ethics Committee and written informed
cases an acute infection or vaccination is consent (conforming to the principles in the
reported to have occurred three to six weeks Helsinki Declaration), patients, admitted in
prior to the neurological symptoms. This is Pediatric Neurology ward or Pediatric
believed to give rise to an abnormal immune Intensive Care Unit (PICU) of Children’s
stimulation that attacks peripheral nerve Medical Center in Tehran, from October 2004
tissue. The optimal treatment of GBS in to November 2006 were recruited. Children
children based on its availability and similar from the age of independent walking to 16
results to plasma exchange is intravenous years were eligible. Inclusion and exclusion
immunoglobulin (IVIg) in patients who are not criteria were based on the published
able to walk. Overall, it is believed that international research diagnostic criteria of
childhood GBS has a more favorable course Asbury and Cornblath.
and prognosis[11,12]. Different studies have The GBS was clinically diagnosed by a
attempted to identify prognostic factors such consultant neurologist. The clinical and
as age, rate of progression and need for demographic characteristics, including age,
respiratory support with regard to a poor gender, preceding events, presentation at the
outcome. However, most of the studies had time of admission, cranial nerve palsy,
retrospective design and only few of them autonomic dysfunctions, muscle stretch reflex,
were performed prospectively[13,14]. duration of hospital stay, and need for PICU
Neuropathic pain is commonly found setting were recorded in a standardized chart.
among GBS patients. Back, buttock and leg All patients had at least one electro‐
pain have been reported in 32% to 67% of physiological study at the acute period of
cases[2,8]. Several studies have shown that disease and CSF analysis. Nerve conduction
faces pain scales are easily understood by the studies included motor nerve conduction
children and they are more useful compared velocity (MNCV), sensory nerve conduction
with other assessment tools. Functional velocity (SNCV), and F‐wave response studies
Iran J Pediatr. Vol 18 (No1); Mar 2008 13
performed. Each value of MNCV, SNCV, and F‐ Findings
wave latency was compared with age‐matched
normal values. Needle electromyography During a period of 26 months, 45 children
(EMG) was performed in all patients. The including 23 (51.1%) males and 22 (48.9%)
clinical classification of the patients was based females with the confirmed diagnosis of GBS
on the electrophysiological criteria of Asbury enrolled in this study. The mean age was 5.9
and Feasby.[11,12] [3.6] years (range, 1‐15.5 years). The most
In addition to the general supportive common preceding events of the GBS were
managements, specific therapy with IVIg (2 respiratory infections (28 cases, 62.2%),
g/kg body weight for 2‐5 days) alone or in followed by gastrointestinal infections (7
combination with corticosteroid (30 mg/kg/ cases, 15.6%) and non‐specific fever (4 cases,
day intravenous methylprednisolone for 3‐5 8.9%). In six other patients no triggering
days) were administered in case the patients factor was found. The interval between these
were not able to walk. events and onset of disabilities ranged from 0
In all children the functional ability of the to 30 days [mean 12.6 (7.2) days]. The most
patient during the course of the disease was common presenting symptoms were limb
scored with ODS, arm function and pain score weakness and pain, that was seen in 32 (71.1
(Fig 1). These scores were to be recorded %) and 20 (44.4%) of cases respectively. The
prospectively on a standardized form on a average interval from onset to nadir was 4.3
daily schedule during the hospital stay or until (2.4) days (range, 1‐14 days). Deep tendon
independent walking was regained and at reflexes (DTR) were reduced or could not be
each outpatient appointment thereafter. The detected in 24 (53.3%) and 20 (44%) patients,
scores of admission and discharge time were respectively.
recorded to compare functional ability. Cranial nerve involvement was found in 21
Results were reported as the mean (standard (46.7%) children, most commonly as bulbar
deviation) for quantitative variables and weakness (gag reflex abnormalities), followed
percentages for categorical variables. by facial palsy in 7 (15.6%) patients and
Univariate comparisons of nominal data were ophthalmoplegia in 3 (6.7%) others. Only one
performed with the χ2 and Fisher's exact tests, patient had sphincter dysfunction. Autonomic
and those of ordinal and numerical data were dysfunctions were manifested as tachycardia,
performed with the Student’s t test, Mann‐ orthostatic hypotension, pupil abnormality
Whitney U test and Wilcoxon and Sign. Also, and sweating disturbance in 8 (17.8%), 3
analysis of regression was applied to evaluate (6.7%), 1 (2.2%) and 2 (4.4%) cases,
consistency of Ordinal Disability and arm respectively.
function scores. All statistical analyses were Eight patients (17.8%) complained of other
performed by using program package SPSS, sensory symptoms. During admission period
version 13 (SPSS, Chicago, IL) and SAS version all children evaluated for pain and its intensity
9.1 for Windows. with pain faces scale. All children experienced
0 1 2 3 4 5
Fig 1 The Pain Faces Scale based on Smiley scale;
0= Very happy, no hurt, 1= Hurts just a little bit, 2= Hurts a little more, 3= Hurts even more, 4= Hurts
a whole lot, 5= Hurts as much as you can imagine
14 Outcome of GuillainBarre Syndrome in Children. MR Ashrafi, et al
some degree of pain which was severe (score 3‐6; median, 4), respectively (Table 1).
4, 5) in 19 (42%), moderate (score 3) in 22 A lumbar puncture was performed in all
(48.8%) and mild (score: 2) in 4 (8.8%) cases within two weeks of the onset of the
patients. With respect to the functional ability, illness. The CSF protein concentration was
average of arm function score and ODS was raised (>45 mg/dl) in 23 (51.1%) patients.
2.76 (range, 0‐6; median, 3) and 4.13 (range, CSF pleocytosis was not found. According to
Table 1‐ Ordinal Disability, Pain Faces and Arm function scores
Scoring System At presentation At discharged
Ordinal Disability Score
0 Normal 0 0
1 Able to run 0 2
2 Able to walk 5 m unaided 0 26
3 Able to walk with aids 12 15
4 Not able to walk, able to lift legs 16 1
5 Not able to walk, not able to lift legs 16 0
6 Intubated, with artificial ventilation 1 0
Median score 4 a,b 2 a,b
Arm function score
0 Normal 0 0
1 Able to raise arms vertically above 1 9
head with extended elbows
2 Able to raise arms vertically above 6 20
head with flexed elbows
3 Not able to raise hands above head 9 11
but able to raise glass of water to mouth
4 Not able to raise glass of water to 13 0
mouth but able to raise hands to mouth
5 Not able to raise hands to mouth but 10 0
able to grasp small object
6 No functional use of hands 1 0
7 Complete paralysis of arms and hands 1 0
Median score 3 a,b 1 a,b
Pain Faces Scale
0 Very happy, no hurt 0
1 Hurts just a little bit 0
2 Hurts a little more 4
3 Hurts even more 22
4 Hurts a whole lot
5 Hurts as much as you can imagine
a P<0.0001, Wilcoxon and Sign tests comparing the functional scores of each
patients before and after treatment
b P<0.0001, Regression correlation analysis of functional scores (correlation
coeffiecents were 0.607 and 0.526, respectively)
Iran J Pediatr. Vol 18 (No1); Mar 2008 15
Fig 2 Comparison of ordinal disability score before and after treatment
clinical and electrophysiological investigations score ≤2) achieved in 28 (62.2%) patients. The
38 (84.4%) of cases were classified as AIDP, 4 ODS was ranged from 1 to 4 points (mean
(2.2%) as MFS and 1(2.2%) unclassified. Ten 2.34, median 2) at discharge. Arm function
(22.2%) patients were admitted in PICU, and was monitored in 40 patients; its score was ≤2
ventilation support was needed for 2 (0.05%) points in all of them (range, 0‐2; median 1).
of them. All patients received IVIG and 8 of This score was impossible for assessment in
them received intravenous methyl‐ young children. After treatment, all patients
prednisolone, too. The length of hospital stay developed significant improvement of
ranged from 3 to 12 days [mean 6.81 (2.55) functional disability which was assessed by
days]. ODS and arm function scores (Table 1 and Fig
The primary clinical response was 2, 3). One patient died due to respiratory
regaining unaided walking (Ordinal Disability failure (death rate, 2.2%). At presentation, she
Fig 3 Comparison of arm function score before and after treatment
16 Outcome of GuillainBarre Syndrome in Children. MR Ashrafi, et al
had weakness, severe pain (Smiley score: 4), progression of GBS, clinical symptoms, GBS
tachycardia, cranial nerve palsy (II, VII, IX and subtype, and treatment options had no
X) and absent DTR. association with clinical outcome (functional
Data analysis showed that a higher ODS at ability, length of hospital stay and need for
presentation is associated significantly with a ventilation support).
longer hospital stay (regression coefficient:
0.339, P=0.03), higher arm function score
(regression coefficient: 0.407, P<0.001). In
addition, patients with more severe pain Discussion
(higher Smiley scale) had higher ODS at final
assessment (regression coefficient: 0.315, In this study we have investigated the initial
P=0.037). Higher functional arm score was symptoms and the clinical course of GBS
associated significantly with more weakness treated with IVIg. Although the incidence of
(P=0.2), cranial nerve palsy (P=0.01) and DTR Guillain‐Barré syndrome has been increased
decrement (P=0.004). In addition, these in Europe and North America during recent
functional ability scales had consistent results decades in adult group over 40 years of age,
(Table 1). Absent DTR and cranial nerve palsy GBS is a disease affecting mainly the younger
were associated with higher functional scores, age groups of children[18‐20]. However, this
longer hospital stay and admission in PICU high frequency in children was found only in
(Table 2). Also, arm function scores at AIDP form. In our series of 45 pediatric
presentation and discharge was found to be populations, 84.4% had clinical and
higher in patients who needed an intensive electrophysiological findings suggesting AIDP
care setting (medians 4 and 2 versus 3 and 1 which is concordant with previous studies.
for patients without need to intensive care MFS and axonal neuropathy were also
setting, P=0.01). Other characteristics such as diagnosed in 2.2% and 11.1% of patients,
age, gender, preceding events, time to respectively. Apparently, few cases of
Table 2 Association between patient’s characteristics and clinical outcome
Gag reflex Tendon Reflex
Yes No Decrease Absence decrease Normal Yes No
score at presentation 5 4 4 4.5 4 3 4.5a 4
score at discharge 3a 2 2 2 2 1 3a 2
Arm function score
at presentation 4a 2 3 4 2 1 4a 2
Arm function score
at discharge 2a 1 1 1a 1 1 2a 1
LOS (median) 5 10 7 6.5a 7 4 7a 5
PICU setting 4/4 6 8/20 2/24 10/21
0a 0 0
No(%) (100%) (4.9%) (40%)a (8.3%)a (47.6%)a
LOS: Length of hospital stay
a P<0.05, comparing outcome by clinical sings
Iran J Pediatr. Vol 18 (No1); Mar 2008 17
pediatric GBS present as MFS form of ataxia, therapy was applied on admission for all
ophthalmoplegia and arefleixa. Electro‐ patients being able to walk with aids.
physiological classifi‐cation of the GBS However, frequently the clinical course of
subtypes varied in different studies. A recent childhood GBS is less severe than that of GBS
study showed the AIDP, AMAN and among adults and usually recovery is
unclassified forms as 35%, 48% and 16%, complete.
respectively; while most other studies Outcome of GBS is quite good with an
reported the AIDP form as the mainly excellent functional recovery. Many factors
diagnosed one. Male to female ratio was associated with poor outcome are reported in
similar to previous reports[13,18]. In this the clinical studies. These factors are
population, clinical manifestations were advanced age, progressive course and severity
concordant to previous studies. of the illness, the presence of other serious
The majority of patients presented with medical disorders and primary axono‐
limb weakness, which developed in more than pathy[28,31]. In this study, abnormal gag reflex
90% of cases during follow‐up. Overall or other cranial nerve palsies and absent DTR
estimates of pain as an early symptom of GBS were associated significantly with longer
have been reported in 32% to 67% of hospital stay and PICU admission. Also,
cases[2,8]. In this study 42% of our patients patients with cranial nerve palsy, especially
experienced severe pain but some degree of gag reflex abnormality had significantly higher
pain reported in all of them evaluated with Ordinal Disability and arm function scores.
Pain Faces Scale[15,24]. This finding might be There were no significant relationship
due to use of more sensitive and accurate between age, gender, preceding illnesses,
method for measurement of pain in children. clinical symptoms, and duration of
During of the disease and follow up period, the progression,electrophysiological findings and
severity of pain associated significantly with therapeutic regimes and clinical
the severity of motor involvement, indicating a outcome(functional ability,length of hospital
shared involvement of motor and sensory stay and need to ventilation support).
nerve fibers. As a consequence, not only the In contrast to what has been reported
ascending pareses and imminent respiratory previously in adults, in this study no
insufficiency must be regarded as important significant relation between any neuro‐
aspects in the management of a child with physiologic findings and the severity of
GBS, the problem of pain must also be symptoms, or the later course and prognosis
anticipated and treated properly. were found.
Apart from clinical symptoms, the finding of Ventilation support is needed in about 10‐
CSF albumin protein dissociation is one of the 20% of the patients; but respiratory failure
most important diagnostic features in GBS. does not predict a persisting deficit. Mortality
In our group of patients, when patients is low in childhood GBS, the death rate varies
underwent lumbar puncture within two among different series, ranging up to
weeks after initiation of the first symptoms, 13%[14,33]. In this study it was estimated to be
half of the patients showed significantly 5% in an intensive care setting. Although not
elevated CSF protein. Other studies reported significant statistically the deaths seem to
that the protein elevation depends on the date occur more often in the older age group. About
of lumbar puncture from 100 to 60% of the 25% of deaths occur during the first week and
patients[26,27]. Although GBS is often a self‐ about 50% during the first month. Cardiac
limiting illness, it can be associated with arrest as a result of autonomic dysfunction is
severe morbidity and even mortality in few the commonest cause of death and accounts
cases. The results of retrospective studies for about 20–30% of deaths. Other causes of
revealed that IVIG shortened the time to first death include chest infection, pulmonary
improvement and to regain independent embolism, and respiratory failure[2,33‐35]. In
walking[3,4,29,31]. In our study, a standard IVIG our study, only 4.4% cases needed ventilation
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