Guillain–Barre syndrome in North Indian children: Clinical and serial electrophysiological features
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.263191
Source of Support: None, Conflict of Interest: None
Keywords: Erasmus GBS outcome score, Guillain-Barre syndrome, reversible conduction failure, serial electrophysiological studies
Guillain-Barre syndrome (GBS) is an acute onset, immune-mediated polyneuropathy. It includes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and other regional forms. Electrophysiological studies help in confirming the clinical suspicion as well as assigning the electrophysiological subtype. Serial electrophysiological studies may help to ascertain the final correct diagnosis of the subtype., This study aimed to describe the clinical and serial electrophysiological features along with short-term outcomes of children with GBS in north India.
This prospective study was carried out in the Department of Pediatrics at a tertiary care, teaching pediatric hospital in north India from December 2013 to March 2015. Consecutive children, aged 2 to 18 years, with GBS, presenting within 4 weeks of onset of weakness, diagnosed on the basis of clinical , and/or electrophysiological grounds  were included. Children who had received intravenous immunoglobulins prior to presentation or those who refused to participate in the study were excluded. The study was approved by the ethics committee of the institute.
After an informed consent, the eligible children underwent a detailed clinical assessment as per a predesigned performa. Unilateral nerve conduction studies [Motor – median, ulnar, tibial, and common peroneal nerves; sensory – median and ulnar nerve (orthodromic) and sural nerve (antidromic)] were performed at admission (in case of asymmetric weakness clinically, bilateral studies were done). Minimum F-wave latencies were recorded in median, ulnar, tibial, and common peroneal nerves. The values were compared to the age matched values. The distal limb temperatures were routinely recorded and the limbs were warmed, if necessary, to maintain the temperature of >34°C. The technician was blinded to the clinical details of the patient.
The children were classified into AMAN, AMSAN, and AIDP, as per the Hadden criteria. They were classified as “inexcitable” if no compound muscle action potential or sensory nerve action potentials were obtained. Children with GBS were managed as per the standard guidelines., Intravenous immunoglobulins were administered in children who required aid to walk within 4 weeks of onset of symptoms.
Functional ability of the patients was tested by using GBS disability score  and the severity of motor weakness by MRC sum score. These scores were recorded on admission and on discharge. The clinical prognostic scoring system, Erasmus GBS Outcome Score (EGOS), was also computed to determine the risk of nonambulation (unassisted) in the future. It takes into account the GBS disability score at 2 weeks after admission, absence or presence of antecedent diarrhea, and age at onset.
Repeat nerve conduction studies (protocol described as above) were performed after 2 weeks of the first study (within 7 days) by the same technician. The patients were further classified into AMAN, AMAN with reversible conduction failure, AMAN with length dependent conduction failure, AMSAN, or AIDP.
After discharge, the children were followed up clinically after 1 week, 1 month, and 3 months. Functional ability [GBS disability score and MRC sum score] was again assessed at 3 months.
Descriptive statistics (mean/standard deviation (SD)/range/median/interquartile range/percentage) were used to describe the study characteristics. The continuous data were compared using t-test and Wilcoxon rank-sum test. The categorical data were analyzed using chi-square and Fischer-exact tests. STATA 9.0 (StataCorp, Texas, USA)was used for analysis.
During the study period, 37 children were diagnosed as GBS. One child was excluded as he had received intravenous immunoglobulin prior to enrolment. Hence, 36 children were studied. The salient characteristics of the study population are summarized in [Table 1].
Seventeen children (47%) were aged 2 to 10 years of age, and only 2 children were more than 10 years of age.
Cerebrospinal fluid (CSF) examination was performed in 21 patients, of which 16 (76.2%) showed albumin cytological dissociation. The mean protein concentration was 125.7 mg/dL (SD: 80.2). The median number of cells was 0 (range: 0–20).
The electrophysiological subtypes at presentation and repeat studies are shown in [Table 2]. Four children, initially diagnosed as AIDP, had AMAN with reversible conduction failure on the repeat study. The child with normal findings at presentation was diagnosed as AMAN on the repeat study. One child with AMAN initially showed inexcitable nerves on the repeat study. Hence, the final classification was AMAN in 25 (69.4%; 95% CI, 51.9–83.7%) and AIDP in 9 children (25%; 95% CI, 12.1–42.2%).
The children with AIDP were significantly younger than children with AMAN. Other variables were similar between the two groups [Table 3].
One child died during admission due to nosocomial pneumonia. Three children were lost to follow up. Thirty-two cases were available for study at the 3-month follow up.
The distribution of GBS disability score at discharge and at a 3-month follow up is shown in [Table 4]. The mean MRC sum score at a 3-month follow up was 46.7 (SD: 7.9).
The EGOS was 2 in 2 (5.6%), 3 in 5 (13.9%), 4 in 26 (72.2%), and 5 in 3 (8.3%) patients. Only 1 out of 32 patients was nonambulatory at the 3-month follow up; his EGOS was 5.
The present study explored the clinical characteristics, electrophysiological subtypes, and short-term outcomes in children with GBS.
AMAN was the predominant electrophysiological subtype, accounting for 69.4% of patients in this study. Axonal variants have been reported to be the most common subtypes in other studies from India,, China, and Japan. AIDP has been observed to be more common in developed countries.,,,, The reasons for such a distribution remain unclear. No patient was diagnosed as AMSAN in the present study.
The majority of patients had a favorable outcome at the 3-month follow up. The GBS disability score was 1 or 2 in 27 out of 32 (84.4%) children in our study. Similar favorable outcomes have been reported in childhood GBS from India. At a 1-year follow up visit, 87.5% children (n = 40) either recovered fully or had only minimal symptoms in another study from north India. All children (43/43) had a GBS disability score of 1 or 2 at a 6-month follow up visit in a study from south India. Similar favorable outcomes have been reported in 70–75% children from developed countries.,
It has been observed that the axonal variants may exhibit features such as conduction blocks or delayed distal latencies without abnormal temporal dispersion at an earlier electrophysiological study, which may closely mimic features of demyelination. However, these features are transient and rapidly reverse (over days to weeks), as evident on serial studies.,, This has been termed as reversible conduction failure, and may contribute to the over-diagnosis of AIDP if only a single study is performed early in the disease course. This phenomenon has been attributed to antibody-mediated functional or microstructural changes at nodal and paranodal regions.,, Unfortunately, anti-ganglioside antibodies could not be done in this study.
In our study, 4 out of 36 (11.1%) children, who were diagnosed as AIDP on the first study, demonstrated reversible conduction failure and were finally diagnosed as AMAN on the second study. In a study by Sekiguchi et al., 30% patients (n = 156) showed the AIDP pattern at the first examination with the diagnosis changing to AMAN on sequential studies.
Thus, the existing diagnostic criteria for GBS must be modified to incorporate results of serial electrophysiological studies. The timing and frequency of such studies are still unclear. A recent study showed that two serial studies performed within the first 2 weeks and between 3–8 weeks of disease onset are sufficient in elucidating the true electrodiagnosis of GBS. In our study, we performed the second electrophysiological evaluation within 2–3 weeks of the first evaluation.
However, recently, Rajabally et al., proposed a modified set of criteria for the diagnosis of GBS subtype taking into consideration the recently described characteristics of AMAN. They concluded that a single electrophysiological study may suffice to establish the ultimate electrodiagnosis of GBS subtype if these criteria were used.
The limitations of the study included a small sample size and nonavailability of anti-ganglioside antibodies. Despite these limitations, it would be prudent to conclude that AMAN is the most common subtype in this part of the world. Its proportion increases further with serial electrophysiological studies. Majority of children achieve a good outcome irrespective of the GBS subtype. Future research should be aimed at investigating the timing and frequency of serial electrophysiological studies, the role of temporal dispersion as a diagnostic marker, and the electrophysiological patterns in anti-ganglioside positive and negative patients. This would help to formulate more robust diagnostic criteria for the GBS subtypes.
The authors are grateful to the electrophysiological technician, Mr. Manas Guchait.
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Conflicts of interest
There are no conflicts of interest.
[Table 1], [Table 2], [Table 3], [Table 4]