Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 59, Num. 5, 2011, pp. 722-726

Neurology India, Vol. 59, No. 5, September-October, 2011, pp. 722-726

Topic of the Issue: Original Article

Utility of neurophysiological criteria in Guillain Barre΄ syndrome: Subtype spectrum from a tertiary referral hospital in India

M Alexander, AT Prabhakar, S Aaron, M Thomas, V Mathew, AK Patil

Department of Neurological Sciences, Neurology Division, Christian Medical College, Vellore, Tamil Nadu, India
Correspondence Address: M Alexander, Professor of Neurology, Department of Neurological Sciences, Christian Medical College, Vellore 632004, Tamil Nadu, India, mathewalex@cmcvellore.ac.in

Date of Submission: 09-Sep-2011
Date of Decision: 27-Sep-2011
Date of Acceptance: 01-Oct-2011

Code Number: ni11218

PMID: 22019658

DOI: 10.4103/0028-3886.86548

Abstract

Keywords: Acute axonal motor neuropathy, acute inflammatory demyelinating polyradiculoneuropathy, acute motor sensory axonal neuropathy, demyelination, electrophysiological criteria, Guillain Barre' syndrome

Introduction

The Guillain Barre' syndrome (GBS) is the most common cause of acute flaccid paralysis worldwide. ^[1] The classical presentation, progressive areflexic motor weakness and albuminocytological dissociation are the most reliable criteria for the diagnosis. ^[1],[2] Electrophysiological studies have a crucial role in confirming the diagnosis and distinguishing various subtypes: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor sensory axonal neuropathy (AMSAN). It is difficult to distinguish the various subtypes on clinical features alone; emphasizing the importance of electrophysiological studies. ^[3],[4] Most of the electrophysiological criteria are from Western studies where AIDP is more prevalent and hence, most criteria have addressed the diagnosis of AIDP. There are about eight criteria for identification of demyelination in peripheral nerves, however, there is a lack of consensus. ^{[5],[6],[7],[8],[9]} There is paucity of data from the Indian subcontinent and the available data suggests AIDP as the most common subtype. ^[10],[11] Our institute is a tertiary referral centre with referrals from different parts of the country. We aimed to study the spectrum of GBS in our patient population and look at the sensitivity of six published criteria in identifying demyelination and also in distinguishing the axonal forms of the disease.

Materials and Methods

The study included all patients referred to our EMG Laboratory within the four weeks of onset of illness. From a careful review of patient charts, the disability status at the time of the electrophysiological study was graded according to a seven-point scale of motor function. ^[12]

All the patients had nerve conduction studies done on at least six motor and six sensory nerves using conventional techniques. Parameters measured included: distal motor and sensory latencies, motor and sensory conduction velocities, compound action potentials (CMAP), F latencies, and sensory action potentials (SNAPs). The skin temperature was maintained over 32°C. The value of each variable was compared with the upper and lower limits of normal for our laboratory. The individual data was entered into a computer program and the various published criteria were then applied to the patient data [Table - 1]. We also used one criterion used for Chronic Inflammatory Polyradiculoneuropathy, but also used in the setting of GBS. ^[13] All measured segments of all nerves (including entrapment sites) were included for the purpose of applying the various criteria. Statistical tests were done by using Fisher exact test and chi-square tests.

Results

There were a total of 115 patients, 85 adults and 30 children; 84 males and 31 females. The mean age of the total cohort was 31.6 years (mean age for children: 10.1 years and for adults: 39.3 years). Only 7% of patients gave history of antecedent events: upper respiratory infection in 16, diarrhoea in 4, antirabies vaccination in 1, and oral polio vaccination in 1. Of the 115 patients, 27 were in Hughes Grade 1, 16 in Grade 2, 27 in Grade 3, 37 in Grade 4, and 8 in Grade 5 [Figure - 1]. The mean interval between the onsets of illness time to electrophysiological studies was 2.9 weeks. Various treatment modalities the patients received included: plasma exchange in 39%, intravenous Immunoglobulin in 31%, and no specific treatment in 30% of patients [Figure - 2].

A total of 920 nerves were studied: 230 each median, ulnar, peroneal, and sural nerves. Motor conductions were measured over two segments in the median nerves, over three segments in the ulnar nerves and over two segments in the peroneal nerves. Tibial nerve studies were not included as there was no normative data available in our laboratory. Motor distal latencies were abnormal in 43.9% of the nerves tested, CMAP abnormalities in 61.01%, reduced motor conduction velocities in 33.9%, F-wave abnormalities in 30.14% (absent F-waves in 12.2%), conduction block in at least two motor nerves in 17.4%, and abnormal SNAPs in 38.71%. The various published criteria sets were then applied to our patient set [Table - 1]. The criteria proposed by Ho et al., were then used for distinguishing axonal forms of GBS from the AIDP. ^[7] Of the 115 patients, 51 (44.3%) patients had axonal forms of the disease, 35 (30.4%) had AMAN and 16 (13.6%) had AMSAN. Forty-four (38.2%) patients had AIDP and 20 (17.4%) patients remained unclassified [Table - 2].

When Criteria A ^[5] was used, 41 (67.2%) of patients could be categorized to have AIDP. With Criteria B ^[6] 21 (32.8%) were identified to have AIDP. Criteria C ^[13] could identify 15 (23.4%) patients to have AIDP and Criteria D ^[7] identified 37 (57.8%) patients to have AIDP. The Dutch criteria, Criteria E ^[8] identified 40 (62.5%) patients to have AIDP (62.5%), while Criteria F ^[9] identified 32 (50%) patients to have AIDP [Table - 3] and [Figure - 3].

Adults vs. children

Out of the 31 children, 16 (53.3%) had AMAN, when compared to adults, where only 19 (22.4%) had AMAN (P=0.03 ). 8/31(26.3%) children had AIDP, whereas 36 (42.4%) adults had AIDP (P=0.05). Sixteen (16.5%) adults had AMSAN, whereas only two (6.7%) children had AMSAN [Table - 4] and [Table - 5].

Sensory conduction abnormalities

Clinical examination documented sensory changes in 16.5% of patients, while electrodiagnostic studies revealed sensory abnormalities in 46.5% of patients. The difference in sensory conduction abnormalities between AIDP and the axonal variant was significant (59.4% vs. 38.2%, P=0.002). Sensory involvement was more common in adults than children (P=0.019). Sensory involvement was more severe in the AMSAN subtype than AIDP (P=0.03). Abnormal median SNAPs with normal sural SNAPs were seen in 63% of patients.

Discussion

Categorization of GBS into various subtypes is of importance as the pathogenesis, severity of the disease, and prognosis may be different between the various subtypes. ^{[7],[14],[15],[16]} There seems to be a change in the taxonomy of GBS, with a paradigm shift in autoimmune target, from myelin-related epitopes to axolemma; how does the immune-targeting spare or involve the sensory fibres, the antecedent events, resulting in immunological targeting of the specific components of the peripheral nerve; and the retinue of infectious organisms like C. jejuni, the immunological recognition of lipo-oligosaccharide (LOS) on the bacterial cell wall with theproduction of cross reacting antibodies that cross react with the gangliosides present on the axolemmal surface in the peripheral and cranial nerves . There are also geographical differences in the incidence of various subtypes of GBS; while AIDP is more common in the Western population, axonal subtypes are more common in the Asian population. ^{[7],[15],[16],[17],[18]} Identification of AMAN and AMSAN depends on the accurate identification of AIDP. ^[14] Most of the studies are from Western countries and the most widely recognized subtype in these studies is AIDP and most electrodiagnostic criteria depended on the recognition of peripheral nerve demyelination. ^{[5],[6],[7],[8],[9]} However, there is lack of consensus among different investigators for the detection of acute demyelination in peripheral nerves.

In 1985, Albers and co-workers ^[5] modified Kelly's ^[19] criteria for identification of demyelination in peripheral nerves, incorporating lower and upper limits of normal. They reviewed the data of 70 patients and could categorize 71% of patients into AIDP by using this modified criterion. Using this criterion, we could identify 67.2% of patients to have AIDP, while. Alam et al.,^[18] identified 72% of their patients to have AIDP. Using the revised Albers and Kelly ^[6] criteria, only 32.8% of our patients were identified to have AIDP. Alam et al also had a low yield of 37%, using the same criterion., ^[18] Using the criteria proposed by Cornblath et al., ^[13] our study identified only 23.4% to have AIDP, which was similar to the yield in the study by Alam and colleagues. ^[5] Ho et al.,^[7] modified the criteria proposed by Albers et al., ^[6] to differentiate AMAN from AIDP, in their study of GBS patients in China. Using these criteria, our study found 57.8% of the patients to have AIDP. In 1995, the Dutch GBS group evaluated electrophysiological variables in a population of 147 patients with GBS for criteria for demyelination. ^[8] This group had laid emphasis on temporal dispersion and conduction block. ^[20] After testing other criteria, ^[5,6] this group identified 60% of patients to have AIDP on the first day, 66% at the end of the first week and 72% at four weeks. Using the Dutch criteria, 62.5% of our patients were diagnosed to have AIDP. In 1996, an Italian GBS group ^[9] modified criteria for CIDP and used them in their patients with GBS and identified 56% of their patients to have AIDP. By these criteria 50% of our patients were identified to have AIDP.

There had been considerable variation in the yield of AIDP when different sets of criteria were applied to our patients. In the two Chinese studies, ^[4],[7],[21] less than 50% of the patients had AIDP, whereas, the yield of AIDP in European and North America had been about 70%. ^{[5],[6],[7],[8],[9],[10]} Electrodiagnosis could underestimate AIDP, because distal and proximal conduction block, an early finding in AIDP, could be missed. ^[22] Conduction block might be the only finding in AIDP, where criteria requiring changes in parameters If conduction block is the only criterion used, the requirement of two or more parameters in a single nerve may not be fulfilled. Further, the electrophysiological parameters may change over a period of time, as the disease evolves, and thus patients not diagnosed to have AIDP and similarly axonal forms of the disease may be missed, stressing the importance of serial electrophysiological studies. Recently, Uncini et al., ^[23] did at least two serial conduction studies in 55 patients, with a mean duration of 28 days between the tests. They used the criteria proposed by Ho et al.,^[7] and Hadden et al. ^[24] In the first study, 65% and 67% of patients' could be classified to have AIDP, 18% of patients could be classified as to have axonal subtype; and in 14% and 16% of the patients, the results were equivocal . At the follow-up study, there was a change in the classification in 24% of patients': a decrease in AIDP to 58%, an increase in axonal subtype to 38% and a decrease in the equivocal group to 4%. The majority of the shifts were from AIDP and equivocal groups to the axonal subtype. The main reason was that serial recordings were able to recognize the reversible conduction failure and length-dependent CMAP amplitude reduction as an expression of axonal pathology.

In our study, the axonal subtype accounted for 44% of the cases (AMAN: 30.4 % and AMSAN: 13.6 %, while AIDP accounted for 38.2% of the cases. About 17.4% of patients remained unclassified. AMAN accounted for 53.3% of pediatric GBS, whereas only 22.4% of the adults had AMAN. In adults AIDP accounted for 42.4 % of the cases, whereas only 26.3% of the children had AIDP. The frequency of AMSAN in adults and children was 16.5% and 6.7% respectively. On applying the six criteria, the number of patients categorized under the AIDP subtype ranged between 24.2% and 72%. The criteria proposed by Albers et al.,^[5] and the Dutch group ^[8] were the most sensitive criteria in identifying AIDP. In the study by Alam et al., ^[18] the criteria proposed by Albers et al., ^[5] were found to be the most sensitive criteria. In the studies from India AIDP was found to be more common. ^[10],[11] In the north Indian study the distribution of GBS subtypes was: AIDP in 86.3%, AMAN in 7.8%, and AMSAN in 6.7%. ^[10] The distribution of GBS subtypes in the south Indian study was: AIDP in 85.2%, axonal variants in 10.6%, and 4.2% were unclassifiable. ^[11] This difference between our study and the other two Indian studies is most probably due to the fact that our study had more children and in children AMAN was more common than in adults (53.4% vs. 22.4%). The limitations of our study are that the electrophysiological studies were cross-sectional and we have not done serology for antecedent infections.

References

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