Iranian Journal of Pediatrics Tehran University of Medical Sciences Press ISSN: 1018-4406 EISSN: 2008-2150 Vol. 18, Num. 1, 2008, pp. 11-19

Iranian Journal of Pediatrics, Vol. 18, No. 1, March, 2008, pp. 11-19

Clinical Short Term Outcome of Guillain-Barré 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

¹Department of Pediatrics, Medical Sciences/University of Tehran, Iran
* Correspondence author; Address: Division of Pediatric Neurology, Children’s Medical Center, 62 Gharib St, 14194 Tehran, IR Iran, E-mail: dr.ssagheb@yahoo.com

Received: 14/08/07; Revised: 01/11/07; Accepted: 04/12/07

Code Number: pe08002

Abstract

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 mortality.
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; ArmFunction score; Pain scale

Introduction

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy characterized by symmetric ascending weakness and spontaneous remission^[1,2].It is the most common cause of acute flaccid paralysis in children which often leads to respiratory and bulbar compromise^[3,4]. The incidence of the disease has been previously reported to be between 0.4 to 0.6 / 100,000 in western countries and 1.5 to 3.4 / 100,000 in Iran^[5,6].

Based on clinical features and electro­diagnotic criteria GBS can be sub classified into heterogeneous groups of syndromes such as acute inflammatory demyelinating polyradiculo-neuropathy (AIDP), acute motor 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 form with an incidence between 85% to 90% of cases with GBS in spite of Asian studies which report it about 53%^[6-9]. In 70–80 % of cases an acute infection or vaccination is reported to have occurred three to six weeks prior to the neurological symptoms. This is believed to give rise to an abnormal immune stimulation that attacks peripheral nerve tissue^[10]. The optimal treatment of GBS in children based on its availability and similar results to plasma exchange is intravenous immunoglobulin (IVIg) in patients who are not able to walk^[4]. Overall, it is believed that childhood GBS has a more favorable course and prognosis^[11,12]. Different studies have attempted to identify prognostic factors such as age, rate of progression and need for respiratory support with regard to a poor outcome. However, most of the studies had retrospective design and only few of them were performed prospectively^[13,14].

Neuropathic pain is commonly found among GBS patients. Back, buttock and leg pain have been reported in 32% to 67% of cases^[2,8]. Several studies have shown that faces pain scales are easily understood by the children and they are more useful compared with other assessment tools^[13]. Functional ability of patients at presentation or during the study and its comparison after treatment has been investigated frequently to assess the role of different treatments^[4]. These tests were rarely used as a prognostic factor to predict the patient’s functional outcome, need for ICU admission or length of hospital stay. Moreover, there are limited epidemiological data reported in Asian populations about GBS^[13,16,17].

In this study, we prospectively evaluated the clinical outcome of children with different subtypes of GBS and their functional outcome based on Ordinal Disability Scale (ODS), Arm Function score and Pain Faces Scale (Smiley Scale) to identify prognostic indicators along with cerebro-spinal fluid (CSF) findings and electrophysiological investigations.

Material & Methods

After obtaining approval from the Institutional Ethics Committee and written informed consent (conforming to the principles in the Helsinki Declaration), patients, admitted in Pediatric Neurology ward or Pediatric Intensive Care Unit (PICU) of Children’s Medical Center in Tehran, from October 2004 to November 2006 were recruited. Children from the age of independent walking to 16 years were eligible. Inclusion and exclusion criteria were based on the published international research diagnostic criteria of Asbury and Cornblath.^[12]

The GBS was clinically diagnosed by a consultant neurologist. The clinical and demographic characteristics, including age, gender, preceding events, presentation at the time of admission, cranial nerve palsy, autonomic dysfunctions, muscle stretch reflex, duration of hospital stay, and need for PICU setting were recorded in a standardized chart.

All patients had at least one electro­physiological study at the acute period of disease and CSF analysis. Nerve conduction studies included motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), and F-wave response studies performed. Each value of MNCV, SNCV, and F-wave latency was compared with age-matched normal values. Needle electromyography (EMG) was performed in all patients. The clinical classification of the patients was based on the electrophysiological criteria of Asbury and Feasby.^[11,12]

In addition to the general supportive managements, specific therapy with IVIg (2 g/kg body weight for 2-5 days) alone or in combination with corticosteroid (30 mg/kg/ day intravenous methylprednisolone for 3-5 days) were administered in case the patients were not able to walk.  

In all children the functional ability of the patient during the course of the disease was scored with ODS, arm function and pain score (Fig 1). These scores were to be recorded prospectively on a standardized form on a daily schedule during the hospital stay or until independent walking was regained and at each outpatient appointment thereafter. The scores of admission and discharge time were recorded to compare functional ability. Results were reported as the mean (standard deviation) for quantitative variables and percentages for categorical variables. Univariate comparisons of nominal data were performed with the χ² and Fisher's exact tests, and those of ordinal and numerical data were performed with the Student’s t test, Mann-Whitney U test and Wilcoxon and Sign. Also, analysis of regression was applied to evaluate consistency of Ordinal Disability and arm function scores. All statistical analyses were performed by using program package SPSS, version 13 (SPSS, Chicago, IL) and SAS version 9.1 for Windows.

Findings

During a period of 26 months, 45 children including 23 (51.1%) males and 22 (48.9%) females with the confirmed diagnosis of GBS enrolled in this study. The mean age was 5.9 [3.6] years (range, 1-15.5 years). The most common preceding events of the GBS were respiratory infections (28 cases, 62.2%), followed by gastrointestinal infections (7 cases, 15.6%) and non-specific fever (4 cases, 8.9%). In six other patients no triggering factor was found. The interval between these events and onset of disabilities ranged from 0 to 30 days [mean 12.6 (7.2) days]. The most common presenting symptoms were limb weakness and pain, that was seen in 32 (71.1 %) and 20 (44.4%) of cases respectively. The average interval from onset to nadir was 4.3 (2.4) days (range, 1-14 days). Deep tendon reflexes (DTR) were reduced or could not be detected in 24 (53.3%) and 20 (44%) patients, respectively.

Cranial nerve involve­ment was found in 21 (46.7%) children, most commonly as bulbar weakness (gag reflex abnormalities), followed by facial palsy in 7 (15.6%) patients and ophthalmo­plegia in 3 (6.7%) others. Only one patient had sphincter dysfunction. Autonomic dysfunctions were manifested as tachycardia, orthostatic hypotension, pupil abnormality and   sweating   disturbance   in  8  (17.8%),  3 (6.7%), 1 (2.2%) and 2 (4.4%) cases, respectively.

Eight patients (17.8%) complained of other sensory symptoms. During admission period all children evaluated for pain and its intensity with pain faces scale. All children experienced some degree of pain which was severe (score 4, 5) in 19 (42%), moderate (score 3) in 22 (48.8%) and mild (score: 2) in 4 (8.8%) patients. With respect to the functional ability, average of arm function score and ODS was 2.76 (range, 0-6; median, 3) and 4.13 (range, 3-6; median, 4), respectively (Table 1).   

A lumbar puncture was performed in all cases within two weeks of the onset of the illness.  The  CSF  protein  concentration was raised (>45 mg/dl) in 23 (51.1%) patients.  CSF pleocytosis was not found. According to

Table 1- Ordinal Disability, Pain Faces and Arm function scores

^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)

clinical and electrophysiological investigations 38 (84.4%) of cases were classified as AIDP, 4 (2.2%) as MFS and 1(2.2%) unclassified. Ten (22.2%) patients were admitted in PICU, and ventilation support was needed for 2 (0.05%) of them. All patients received IVIG and 8 of them received intravenous methyl­prednisolone, too. The length of hospital stay ranged from 3 to 12 days [mean 6.81 (2.55) days].

The primary clinical response was regaining unaided walking (Ordinal Disability score ≤2) achieved in 28 (62.2%) patients. The ODS was ranged from 1 to 4 points (mean 2.34, median 2) at discharge. Arm function was monitored in 40 patients; its score was ≤2 points in all of them (range, 0-2; median 1). This score was impossible for assessment in young children. After treatment, all patients developed significant improvement of functional disability which was assessed by ODS and arm function scores (Table 1 and Fig 2, 3).  One   patient  died  due  to   respiratory failure (death rate, 2.2%). At presentation, she had weakness, severe pain (Smiley score: 4), tachycardia, cranial nerve palsy (II, VII, IX and X) and absent DTR.

Data analysis showed that a higher ODS at presentation is associated significantly with a 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 (higher Smiley scale) had higher ODS at final assessment (regression coefficient: 0.315, P=0.037). Higher functional arm score was associated significantly with more weakness (P=0.2), cranial nerve palsy (P=0.01) and DTR decrement (P=0.004). In addition, these functional ability scales had consistent results (Table 1). Absent DTR and cranial nerve palsy were associated with higher functional scores, longer hospital stay and admission in PICU (Table 2). Also, arm function scores at presentation and discharge was found to be higher in patients who needed an intensive care setting (medians 4 and 2 versus 3 and 1 for patients without need to intensive care setting, P=0.01). Other characteristics such as age, gender, preceding events, time to progression of GBS, clinical symptoms, GBS subtype, and treatment options had no association with clinical outcome (functional ability, length of hospital stay and need for ventilation support).

Discussion

In this study we have investigated the initial symptoms and the clinical course of GBS treated with IVIg. Although the incidence of Guillain-Barré syndrome has been increased in Europe and North America during recent decades in adult group over 40 years of age, GBS is a disease affecting mainly the younger age groups of children^[18-20]. However, this high frequency in children was found only in AIDP form^[21]. In our series of 45 pediatric populations, 84.4% had clinical and electrophysiological findings suggesting AIDP which is concordant with previous studies.^[9] MFS and axonal neuropathy were also diagnosed in 2.2% and 11.1% of patients, respectively. Apparently, few cases of

Table 2- Association between patient’s characteristics and clinical outcome

OS: Length of hospital stay     
^a P<0.05, comparing outcome by clinical sings

pediatric GBS present as MFS form of ataxia, ophthalmoplegia and arefleixa^[2]. Electro­physiological classifi-cation of the GBS subtypes varied in different studies. A recent study showed the AIDP, AMAN and unclassified forms as 35%, 48% and 16%, respectively;^[22] while most other studies reported the AIDP form as the mainly diagnosed one^[23]. Male to female ratio was similar to previous reports^[13,18]. In this population, clinical manifestations were concordant to previous studies.

The majority of patients presented with limb weakness, which developed in more than 90% of cases during follow-up. Overall estimates of pain as an early symptom of GBS have been reported in 32% to 67% of cases^[2,8]. In this study 42% of our patients experienced severe pain but some degree of pain reported in all of them evaluated with Pain Faces Scale^[15,24]. This finding might be due to use of more sensitive and accurate method for measurement of pain in children. During of the disease and follow up period, the severity of pain associated significantly with the severity of motor involvement, indicating a shared involvement of motor and sensory nerve fibers. As a consequence, not only the ascending pareses and imminent respiratory insufficiency must be regarded as important aspects in the management of a child with GBS, the problem of pain must also be anticipated and treated properly^[25].

Apart from clinical symptoms, the finding of CSF albumin protein dissociation is one of the most important diagnostic features in GBS^[5]. In our group of patients, when patients underwent lumbar puncture within two weeks after initiation of the first symptoms, half of the patients showed significantly elevated CSF protein. Other studies reported that the protein elevation depends on the date of lumbar puncture from 100 to 60% of the patients^[26,27]. Although GBS is often a self-limiting illness, it can be associated with severe morbidity and even mortality in few cases^[28]. The results of retrospective studies revealed that IVIG shortened the time to first improvement and to regain independent walking^[3,4,29,31]. In our study, a standard IVIG therapy was applied on admission for all patients being able to walk with aids. However,    frequently   the clinical course of childhood GBS is less severe than that of GBS among adults and usually recovery is complete^[28].

Outcome of GBS is quite good with an excellent functional recovery. Many factors associated with poor outcome are reported in the clinical studies^[7]. These factors are advanced age, progressive course and severity of the illness, the presence of other serious medical disorders and primary axono­pathy^[28,31]. In this study, abnormal gag reflex or other cranial nerve palsies and absent DTR were associated significantly with longer hospital stay and PICU admission. Also, patients with cranial nerve palsy, especially gag reflex abnormality had significantly higher Ordinal Disability and arm function scores. There were no significant relationship between age, gender, preceding illnesses, clinical symptoms, and duration of progression,electrophysiological findings and therapeutic regimes and clinical outcome(functional ability,length of hospital stay and need to ventilation support).

In contrast to what has been reported previously in adults, in this study no significant relation between any neuro­physiologic findings and the severity of symptoms, or the later course and prognosis were found.

Ventilation support is needed in about 10-20% of the patients; but respiratory failure does not predict a persisting deficit. Mortality is low in childhood GBS, the death rate varies among different series, ranging up to 13%^[14,33]. In this study it was estimated to be 5% in an intensive care setting. Although not significant statistically the deaths seem to occur more often in the older age group. About 25% of deaths occur during the first week and about 50% during the first month. Cardiac arrest as a result of autonomic dysfunction is the commonest cause of death and accounts for about 20–30% of deaths. Other causes of death include chest infection, pulmonary embolism, and respiratory failure^[2,33-35]. In our study, only 4.4% cases needed ventilation support, one of these children died due to respiratory failure under ventilator (death rate, 2.2%).

Conclusion

Our study provides further information on the extent to which abnormal neurological features impact on the final disability and hospital care setting in comparison with other variables. The Ordinal Disability and arm function scores at the onset of the disease had significant prognostic value factor for clinical short-term outcome in our patients.

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