Guillain–Barré Syndrome in India: Population-based validation of the Brighton criteria

Abstract

Objective

Case definitions of GBS were recently developed in response to the 2009 H1N1 vaccination programme but have undergone limited field testing. We validate the sensitivity of the Brighton Working Group case definitions for Guillain–Barré Syndrome (GBS) using a population-based cohort in India.

Methods

The National Polio Surveillance Unit of India actively collects all cases of acute flaccid paralysis (AFP) in children <15 years old, including cases of GBS. Cases of GBS with available cerebrospinal fluid (CSF) and nerve conduction studies (NCS) results, neurological examination, clinical history, and exclusion of related diagnoses were selected (2002–2003). Relevant data were abstracted and entered into a central database. Sensitivity of the Brighton GBS criteria for level 3 of diagnostic certainty which requires no clinical laboratory testing, level 2 which employs CSF or NCS, and level 1 which employs both, were calculated.

Results

79 cases of GBS (mean age 6.5 years, range 4.0–14.5; 39% female) met the case definition. GBS cases were ascending (79%), symmetrical (85%), and bilateral (100%); involving lower extremity hypotonia (86%) and weakness (100%), upper extremity hypotonia (62%) and weakness (80%), areflexia/hyporeflexia (88%), respiratory muscles (22%), bulbar muscles (22%), and cranial nerves (13%). Four limbs were involved in 80% of cases. Mean time to maximal weakness was 5.2 days (range 0.5–30 days) with nadir GBS disability scores of 3 (7%), 4 (67%), 5 (15%), 6 (10%), or unclear (1%). CSF (mean time to lumbar puncture 29 days) was normal in 29% with cytoalbuminologic dissociation in 65% (mean protein 105 mg/dL, range 10–1000; mean cell count 11/μL, range 0–220, n = 4 with >50 cells/μL). Significant improvement occurred in 73% whereas death (9%) occurred 6–29 days after sensorimotor symptom onset. The majority of cases (86%) fulfilled Brighton level 3, level 2 (84%), and level 1 (62%) of diagnostic certainty.

Conclusion

The diagnosis of GBS can be made using Brighton Working Group criteria in India with moderate to high sensitivity. Brighton Working Group case definitions are a plausible standard for capturing a majority of cases of GBS in field operations in low income settings during AFP surveillance.

Introduction

Guillain–Barré Syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy and an important cause of acute flaccid paralysis (AFP) worldwide [1]. The number of cases of GBS increased following vaccination with the A76NJ 1976 influenza vaccine [2], [3], leading to heightened awareness of GBS. There is a need for a valid, reliable, practical, and global consensus definition of GBS at various levels of certainty especially when new vaccines are developed and provided to large populations [4]. Several case definitions of GBS existed prior to the 2009 H1N1 vaccination campaign including the widely employed Asbury–Cornblath case definitions, which involve ancillary diagnostic tests [5], [6]. More recently, the Brighton Collaboration developed case definitions of GBS with differing levels of diagnostic certainty [7]. These case definitions have undergone limited field testing, particularly in resource-poor settings.

GBS may be especially difficult to diagnose in resource-poor settings. Since the Brighton criteria include purely clinical case definitions as well as categories requiring further specialized testing, the need for additional resources to achieve diagnostic certainty for GBS could be challenging for large resource-poor populations.

In India, there is limited information available on the relative burden of GBS, particularly at a population level. Small case series of patients with GBS in India suggest that it may be an important cause of non-poliomyelitis AFP, including fatal AFP [8], [9], [10]. It is unknown whether the axonal subgroups, mainly acute motor axonal neuropathy (AMAN), are more common than the acute inflammatory demyelinating polyneuropathy (AIDP) form, as has been seen in other developing countries [11], [12], [13]. Based on nation-wide active surveillance data of AFP established by the global polio eradication initiative in India since 1997, we present a population-based cohort study of GBS in Indian children. We answer the following questions: (1) what are the epidemiological, clinical, laboratory, and electrophysiologic features of a subset of Indian children with GBS; and (2) what is the sensitivity of Brighton diagnostic criteria for GBS in children in India?