Guillain-Barré syndrome: subtypes and predictors of outcome from India

Journal of the Peripheral Nervous System 19:36 43 (2014) RESEARCH REPORT Guillain-Barré syndrome: subtypes and predictors of outcome from India Jayantee Kalita, Usha K. Misra, Gaurav Goyal, and Moromi Das Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India Abstract There is a paucity of large studies evaluating the subtypes of Guillain-Barré syndrome (GBS) and their outcome from Southeast Asia. We report cliniconeurophysiological subtypes of GBS and their correlation with triggering events and 3-month outcome from northern India. Three hundred and twenty eight consecutive patients with GBS were clinically evaluated, including their triggers, severity, autonomic involvement, cranial nerve palsy, and respiratory paralysis. Nerve conduction study (NCS) was repeated at 3 weeks if the initial study was normal. They were categorized into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), inexcitable motor nerve, and equivocal. Clinically, 204 (62.2%) patients had pure motor, 106 (32.3%) motor sensory, 16 (4.9%) Miller Fisher syndrome, and 2 (0.6%) pure sensory GBS. Based on NCS, 242 (73.8%) had AIDP, 44 (13.4%) AMAN, 15 (4.6%) AMSAN, 8 (2.4%) inexcitable motor nerves, and 27 (8.2%) equivocal GBS. AIDP patients were older, more common in summer, had lesser peak disability, and better outcome compared to those with AMAN. Eleven (3.4%) patients died and 48 (14.6%) had poor outcome at 3 months. The poor outcome was related to severity, dysautonomia, and inexcitable motor nerves. AIDP is the commonest variant of GBS in our study and has better outcome compared to AMAN. Key words: AIDP, AMAN, AMSAN, GBS, Miller Fisher syndrome, nerve conduction study, outcome, pure sensory Introduction Guillain-Barré syndrome (GBS) is an acute, immune-mediated disorder of peripheral nerves prevalent all over the world with an incidence of 1.2 2.3 per 100,000 persons per year (van Doorn et al., 2008). GBS has been categorized into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), Miller Fisher syndrome (MFS), and pure sensory and Address correspondence to: Prof. Jayantee Kalita, Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, India. Tel: +91 522 2494167; Fax: +91-522-2668811; E-mail: jayanteek@yahoo.com; jkalita@sgpgi.ac.in. pandysautonomic types. The frequency of different GBS subtypes has regional and ethnic variations. In Western Europe, North America, and Australia, AIDP constitutes 80% 90% of GBS in children and adults (Van Koningsveld et al., 2000; Nachamkin et al., 2007). In contrast, high frequency of AMAN has been reported in Japan, Pakistan, India, China, and Mexico ranging from 28% to 67% (McKhann et al., 1993; Gupta et al., 1994; Paradiso et al., 1999; Ogawara et al., 2000; Shafqat et al., 2006; Islam, 2010; Kannan et al., 2011). Moreover, there is seasonal clustering that may be a reflection of preceding infection during that season (Nachamkin et al., 2007; Islam et al., 2010; Kannan et al., 2011). Most of the reports from developing regions are based on relatively small sample size and the extent of clinical and electrodiagnostic 2014 Peripheral Nerve Society 36

evaluation is variable. A detailed evaluation of GBS patients from northern India is limited to a few reports based on smaller sample size (Bansal et al., 2001; Kalita et al., 2001; Sinha et al., 2007; Kalita et al., 2008; Sharma et al., 2011). In this study, we report the clinical and neurophysiological subtypes of GBS and their outcome predictors. We also compare the triggering events, seasonal clustering, clinical findings, and 3-month outcome in patients with AIDP and AMAN. Patients and Methods Consecutive patients with GBS registered prospectively between 2000 and 2012 have been analyzed. These patients were evaluated with a uniform clinical and diagnostic protocol because two of the authors (J. K. and U. K. M.) have been personally involved in the management of these patients. Some of these patients have also been included in our earlier reports (Bansal et al., 2001; Kalita et al., 2001; Das et al., 2004; Kalita et al., 2008). The diagnosis of GBS was based on National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria (Asbury and Cornblath, 1990). Although pure sensory and MFS/MFS-GBS overlap syndrome does not fit in NINCDS criteria of GBS, these subtypes were also included in this study. Exclusion Patients with hypo- or hyperkalemic paralysis, porphyria, viral myositis, poliomyelitis, botulism, diphtheritic neuropathy, and history of potential toxic exposure were excluded. Evaluation The patients were subjected to detailed clinical evaluation. History of preceding sore throat, fever, urinary tract infection, diarrhea, vomiting, vaccination, rash, insect bite, childbirth, and surgery were noted. Cranial nerve palsy was recorded. Muscle power was graded on a 0 5 Medical Research Council (MRC) scale and tendon reflexes were graded as absent, reduced, normal, or brisk. Autonomic dysfunctions such as resting tachycardia, hypertension, fluctuation in blood pressure, absence of sinus arrhythmia, sweating abnormality, and bowel and bladder dysfunction were noted in all and postural hypotension was assessed in patients who could stand or sit. The worst clinical disability was graded on a 0 10 scale as follows (Hahn et al., 1996): 0 = Normal 1 = No disability with motor sensory sign or areflexia 2 = Mild disability-ambulatory for >200 m, mild weakness in one or more limb and sensory impairment 3 = Moderate disability-ambulatory for >50 m without stick, moderate weakness MRC grade 4 and sensory impairment 4 = Severe disability-able to walk >10 m with support of study, motor weakness MRC grade 4 and sensory impairment 5 = Requires support to walk 5 m, marked motor and sensory signs 6 = Cannot walk 5 m, able to stand unsupported and able to transfer to wheelchair, able to feed independently 7 = Bed ridden, severe quadriparesis, maximum strength MRC grade 3 8 = Respiratory and/or severe quadriparesis, maximum strength MRC grade 2 9 = Mechanical ventilation and quadriplegia 10 = Dead Laboratory investigations Complete blood counts, urinalysis, hemoglobin, erythrocyte sedimentation rate in the first hour, fasting blood sugar, blood urea nitrogen, serum electrolytes, creatinine, bilirubin, transaminases and creatine kinase (CK-MM), HIV serology, urine for porphobilinogen, electrocardiogram, and radiograph of chest were carried out. Nerve conduction study was performed on the day of admission. If the initial nerve conduction study was normal, it was repeated in the third week of illness to categorize GBS subtypes. Motor nerve conduction studies of median, ulnar, peroneal, and F waves were recorded bilaterally. Sensory conduction study of median, ulnar, and sural nerves were also performed bilaterally. The abnormality in the nerve conduction study was defined on the basis of our laboratory normative data (Misra and Kalita, 2006). Cerebrospinal fluid (CSF) was examined for cells, protein, and sugar in all the patients to document albuminocytological dissociation. Types of GBS On the basis of clinical examination, the patients were classified into four types: Pure motor Motor sensory Pure sensory MFS/MFS-GBS overlap syndrome. Based on nerve conduction study (NCS), these patients were grouped into: AIDP: If two or more nerves showed demyelinating features (distal latency prolongation, slow nerve conduction velocity, conduction block, or prolonged F wave latency) on motor nerve conduction study (Hadden et al., 1998). 37

AMAN: Normal sensory conduction studies and unrecordable or reduced compound muscle action potential on motor nerve conduction study. There should not be more than one demyelinating feature in any nerve (Hadden et al., 1998). AMSAN: If both motor and sensory nerve conduction studies revealed features of axonal neuropathy such as reduced or absent CMAP and SNAP, marginal slowing or normal conduction velocity and absence of conduction block (Uncini et al., 2009). Inexcitable: Absent CMAP in all motor nerves (or present in only one nerve with CMAP <10% of lower limit of normal) (Hadden et al., 1998). Equivocal: GBS patients not fulfilling the above neurophysiologic criteria (Hadden et al., 1998). Treatment The patient presenting within 14 days of illness with significant weakness (unable to walk unaided) who could afford was prescribed intravenous immunoglobulin (IVIg) 400 mg/kg/day for 5 days. Symptomatic treatment and nursing care were given to all. Patients who were unable to maintain PO 2 > 60 mm Hg and developing hypercarbia (PCO 2 > 50 mm of Hg) or abnormal ph on arterial blood gas analysis were artificially ventilated. We have not intubated patients with bulbar weakness without respiratory paralysis. Patients with bulbar weakness were fed by nasogastric tube. Outcome Outcome at 3 months was categorized as complete (independent for activities of daily living), partial (needing help for activity of daily living), and poor (bedridden or wheelchair bound) (Kalita et al., 2008). Death during this period and the causes of death were noted. Death and lost to follow-up were also included in the poor outcome group for statistical analysis. Statistical analysis The demographic, preceding events (triggers), seasonal clustering, and peak disability in patients with AIDP and AMAN were compared using various parametric and nonparametric tests. The predictors of outcome at 3 months were evaluated by univariate followed by multivariate analysis. In the multivariate analysis, the independent variables having a p value of <0.1 were included. The variables having a two-tailed p value of <0.05 were considered significant. The statistical analysis was performed using SPSS 12 version software. Figure 1. Age-wise distribution of Guillain-Barré syndrome. Figure 2. Distribution of Guillain-Barré syndrome subtypes according to seasons. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) patients were more frequent in rainy season compared to AMAN (p = 0.04) and AMAN patients in the summer (p = 0.01). Results There were 328 patients with GBS whose median age was 30 (1 72) years and 247 were males. Eighty-five of them were below the age of 15 years and 22 were above 60 years with highest frequency during second and fourth decade (Fig. 1). The patients were admitted after a median duration of 8 (1 28) days. The commonest preceding event was fever without localization (22.3%) followed by sore throat (20.7%), diarrhea (19.4%), vaccination (1.2%), exanthematous illness (0.9%), preceding surgery (0.9%), and urinary tract infection (0.6%). Preceding insect bite (0.3%) and childbirth (0.3%) were rare. One patient each had received tetanus and Japanese encephalitis virus vaccine earlier. GBS patients were admitted throughout the year but were more frequent in rainy seasons. The records about seasonal occurrence were available in 324 patients and their seasonal distribution is shown in Fig. 2. AIDP patients were more frequent in rainy season compared to AMAN (25.7% vs. 11.1%; p = 0.04) and AMAN patients in the summer (22.5% vs. 42.2%; p = 0.01; Fig. 2). Bilateral facial weakness was present in 44.2%, bulbar weakness in 30.2%, 38

Table 1. Demographic and clinical characteristics of patients with Guillain-Barré syndrome. Variables Total number = 328 Age, years (median, range) 30 (1 72) Female 81 (24.7%) Extreme age category 15 years 85 (25.9%) 60 years 22 (6.7%) Hospital admission (day of illness) 10.6 ± 8.9 (median 8) Preceding illness 219 (66.8%) Respiratory tract infection 68 (20.7%) Diarrhea 64 (19.4%) Exanthematous illness 3 (0.9%) Fever without localization 73 (22.3%) Vaccination 4 (1.2%) Urinary tract infection 2 (0.6%) Preceding surgery 3 (0.9%) Insect bite 1 (0.3%) Preceding childbirth 1 (0.3%) Cranial nerve involvements 173 (52.7%) Facial palsy 145 (44.2%) Bulbar Palsy 99 (30.2%) Ophthalmoplegia 16 (4.9%) Hypoglossal palsy 6 (1.8%) Sensory symptoms 173 (52.7%) DTR Generalized areflexia 242 (73.8%) At least one retained DTR 65 (19.8%) Retained DTR 17 (5.2%) Brisk DTR 4 (1.2%) Upper limb power <3 Grade 89 (27.1%) 3 Grade 239 (72.9%) Lower limb power <3 Grade 148 (45.1%) 3 Grade 180 (54.9%) Dysautonomia 67 (20.4%) Bladder/bowel involvement 32 (9.8%) Labile hypertension 42 (12.8%) Respiratory involvement 100 (30.5%) Mechanical ventilation 43 (13.1%) CSF albuminocytological dissociation 223 (68%) IVIg treatment 110 (33.5%) Recovery at 3 months Complete 153 (46.6%) Partial 114 (34.8%) Wheelchair bound 48 (14.6%) Dead 11 (3.4%) Lost to F/U 2 (0.6%) DTR, deep tendon reflexes; F/U, follow-up; IVIg, intravenous immunoglobulin. ophthalmoplegia in 4.9%, and hypoglossal weakness in 1.8% of patients. Tendon reflexes were absent in 73.8% and brisk in 1.2%. Craniospinal MRI was done in three patients who had hyperreflexia and was normal. Autonomic dysfunction was present in 20.4% of patients. Forty-three (13.1%) patients had respiratory paralysis requiring artificial ventilation for a median duration of 18.5 (1 66) days. Demographic, clinical, and electrophysiological findings of the patients have been summarized in Table 1. IVIg was prescribed to 110 (33.5%) patients only. Fifty-four patients admitted after Table 2. Clinical and neurophysiological subtypes of GBS. Subtypes N (%) Clinical subtypes Pure motor 204 (62.2) Sensorimotor 106 (32.3) Pure sensory 2 (0.6) MFS/MFS-GBS variant 16 (4.9) GBS electrophysiological subtypes AIDP 242 (73.8) AMAN 44 (13.4) AMSAN 15 (4.6) Inexcitable 8 (2.4) Equivocal 19 (5.8) AIDP, acute inflammatory demyelinating polyradiculoneuropathy; AMAN, acute motor axonal neuropathy; AMSAN, acute motor sensory axonal neuropathy; GBS, Guillain-Barré syndrome; MFS, Miller Fisher syndrome. 15 days of illness and 15 had mild illness; therefore, IVIg treatment was not considered in them. Although IVIg was indicated in the remaining 151 patients, it could not be given because of cost. GBS subtypes On clinical evaluation, GBS was of pure motor type in 204 (62.2%), motor sensory in 106 (32.3%), MFS/MFS-GBS overlap variant in 16 (4.9%), and pure sensory in 2 (0.6%) patients. Both the patients with pure sensory GBS had normal power in limbs with impairment of pain, touch, temperature, vibration, and joint position sense. On walking, both the patients had sensory ataxia. Based on electrodiagnostic criteria, 242 (73.8%) patients had AIDP, 44 (13.4%) AMAN, 15 (4.6%) AMSAN, 8 (2.4%) inexcitable motor nerves, and 19 (5.8%) equivocal GBS (Table 2). Following electrodiagnostic studies, 138 (57%) patients with clinically pure motor GBS were diagnosed as AIDP. Both the patients with pure sensory GBS had demyelinating features in motor nerves. All sensory potentials were unrecordable in one patient and low SNAP with normal latency and velocity in two sensory nerves and unrecordable potentials in the rest of the sensory nerves in the other patient. Both these patients with clinically pure sensory GBS were therefore classified as AIDP after electro-diagnostic study. Outcome At 3 months, 11 (3.4%) patients died, 46.6% had complete recovery, 34.8% had partial outcome, and 14.6% had poor outcome. Causes of death were sudden cardiac arrest, pneumonia, and septicemia. Two patients could not be followed up. Comparison of subgroups The AIDP patients were significantly older (median age 33 vs. 22 years; p = 0.001) and had less frequent 39

Table 3. Comparison of demographic and clinical outcome of AIDP and AMAN. Variable AIDP (n = 242) AMAN (n = 44) p value Age, years (median, range) 33 (2 72) 22 (1 56) 0.001 Female 61 8 0.32 Day of illness at admission (median days) 10.7 ± 9.3 (8 days) 9.6 ± 6.6 (7.5 days) 0.45 Preceding illness Upper respiratory tract infection 55 6 0.25 Diarrhea 39 15 0.005 Exanthematous illness 2 1 0.39 Fever without localization 57 6 0.21 Vaccination 4 0 Urinary tract infection 2 0 Preceding surgery 3 0 Insect bite 1 0 Preceding childbirth 0 1 Cranial nerve palsy 127 23 0.98 Dysautonomia 47 8 0.85 Respiratory involvement 72 11 0.51 Peak disability grade 6.4 ± 1.7 6.7 ± 1.9 0.27 Upper limb power <3 Grade 51 19 3 Grade 191 25 0.003 Lower limb power <3 Grade 96 28 3 Grade 146 16 0.005 DTR Generalized areflexia 179 28 0.22 At least one retained DTR 49 12 0.39 Retained reflexes (all) 11 4 0.26 Brisk reflexes 3 0 Mechanical ventilation 25 7 0.28 Recovery at 3 months Complete 127 14 0.012 Partial 77 21 0.06 Wheelchair bound 32 7 0.63 Dead 6 1 0.94 Lost to F/U 0 1 AIDP, acute demyelinating polyradiculoneuropathy; AMAN, acute motor axonal neuropathy; DTR, deep tendon reflexes; F/U, follow-up. preceding diarrhea compared to AMAN (16.1% vs. 34.1%; p = 0.005). AIDP patients recovered completely for activities of daily living at 3 months in 127 (52.5%) patients compared to 14 (31.8%) only in AMAN. Gender, day of hospitalization, triggering events other than diarrhea, cranial nerve palsy, dysautonomia, peak disability grade, and ventilator requirement were not significantly different between the two groups. The comparison between AIDP and AMAN is presented in Table 3. Outcome predictors On univariate analysis, short interval between onset to hospital admission (p = 0.039), age >50 years (Odds ratio [OR] 1.96, 95% confidence interval [CI] 0.99 3.86, p = 0.035), cranial nerve palsy (OR 2.1, 95% CI 1.12 3.93, p = 0.012), dysautonomia (OR 3.07, 95% CI 1.59 5.9, p = 0.0002), ventilator requirement (OR 3.58, 95% CI 1.70 7.54, p = 0.0002), peak disability (p = <0.0001), inexcitable motor nerves (OR 14.45, 95% CI 2.55 106.62, p = <0.0001), and high white blood cell count on admission (p = 0.047) were significantly related to poor outcome at 3 months (Table 4). On multivariate analysis, only peak disability grade (OR 0.53, 95% CI 0.29 0.95, p = 0.03), dysautonomia (OR 0.86, 95% CI 0.14 0.84, p = 0.02), and inexcitable motor nerves (OR 0.1, 95% CI 0.01 0.96, p = 0.046) were independently related to poor outcome. IVIg was not related to 3-month outcome. IVIg, however, was given to the more disabled patients (p = 0.001) with bulbar weakness or respiratory compromise (p = 0.001). Discussion This study revealed AIDP as the commonest subtype of GBS occurring in 73.8% of patients followed by AMAN in 13.4%, AMSAN in 4.6%, and inexcitable motor nerves in 2.4%. In 5.8% of GBS patients, nerve conduction study was equivocal. The poor outcome at 3 months was related to peak disability grade, 40

Table 4. Outcome predictors of Guillain-Barré syndrome at 3 months on univariate analysis. Predictors Good outcome (n = 267) Poor outcome (n = 61) Odds ratio (95% CI) p value Age, years (median, range) 30 (1.5 72) 30 (1 70) 0.34 Age 50 years 47 18 1.96 (0.99 3.86) 0.03 Male gender 200 47 1.12 (0.56 2.29) 0.73 Interval between onset and admission 11.1 ± 9.4 8.4± 6.3 0.04 Preceding diarrheal illness 49 15 1.45 (0.71 2.94) 0.27 UL power <3 54 35 5.31 (2.83 9.99) <0.0001 LL power <3 98 50 7.84 (3.73 16.8) <0.0001 Cranial nerve involvement 132 41 2.10 (1.12 3.93) 0.012 Bulbar involvement 96 37 2.75 (1.5 5.06) 0.0004 Generalized areflexia 187 55 3.92 (1.54 10.57) 0.002 Preserved UL DTR 46 4 0.34 (0.1 1.03) 0.058 Dysautonomia 44 23 3.07 (1.59 5.9) 0.0002 Peak disability grade 6.2 ± 1.7 7.6 ± 1.0 <0.0001 Ventilatory requirement 26 17 3.58 (1.70 7.54) 0.0002 Blood leukocyte count/mm 3 10,042 ± 5.7 11,670 ± 5.0 0.047 Inexcitable motor nerves 2 6 14.45 (2.55 106.62) <0.0001 No use of IVIg 143 30 0.84 (0.46 1.52) 0.54 CI, confidence interval; DTR, deep tendon reflexes; LL, lower limb; UL,upper limb. dysautonomia, and inexcitable motor nerves. This is the largest single-center study reporting clinical and neurophysiological subtypes of GBS evaluating their correlation with triggers, seasonal clustering, disability, and outcome. AIDP is the commonest subtype of GBS and its reported frequency from Europe and USA ranges between 80% and 90% (Van Koningsveld et al., 2000; Nachamkin et al., 2007). A higher frequency of AMAN has been reported from the developing countries and Asian countries; from Mexico in 38%, Turkey in 27.8%, southern India in 44.2%, Bangladesh in 56%, Iran in 35%, and Japan in 47% (McKhann et al., 1993; Gupta et al., 1994; Ogawara et al., 2000; Barzegar et al., 2007; Akbayram et al., 2011; Sharma et al., 2011). Some studies from India, however, have reported high incidence of AIDP, which is similar to that of western countries; Kalita et al. (2008) from Uttar Pradesh, India reported incidence of AIDP in 80% and Gupta et al. (2008) from Kerala in 85% of patients with GBS. A patient with GBS may clinically present with pure weakness without sensory symptoms, but on electrodiagnostic study, abnormalities may be apparent in sensory nerves, and there may be features of demyelination in the motor NCS. In our earlier study on 51 patients with GBS, although 60.8% of patients presented clinically with pure weakness, on electro-diagnostic studies 83.9$ of them had AIDP (Kalita et al., 2008). In this study, also only one-third of patients with pure weakness had AMAN and the remaining had AIDP. These results highlight the importance of detailed and sequential nerve conduction study for appropriate subtyping of GBS (Kalita et al., 2008; Uncini and Yuki, 2009). The yield of NCS in the diagnosis of GBS varies depending on the time of illness and the criteria of neurophysiological features needed for AIDP. In a study, six sets of neurophysiological criteria for the diagnosis of GBS were used; in the first week, the yield was 32% 88%, which increased to 60% 100% in the third week (Kalita et al., 2008). Recently, classification of sensory GBS and related disorders has been proposed (Uncini and Yuki, 2012). This classification is based on small case series and its significance is uncertain. Sensory GBS is a rare entity and only 0.6% of patients had sensory GBS in this study. According to the proposed classification, both the patients with sensory GBS fit into AIDP subtype. The type of GBS may be related to the antecedent event. Campylobacter jejuni is commonly associated with AMAN and anti-gmi and anti-gdia IgG antibodies have been reported in 30% 40% of AMAN patients (McKhann et al., 1993; Ho et al., 1995; Uncini et al., 2009). In our study, 66.8% of patients had an antecedent illness and diarrheal illness was present in only 19.4% of patients. Diarrhea was more commonly associated with AMAN. In a study from Bangladesh, 36% of GBS patients had preceding diarrhea and 92% of patients had pure motor GBS. Neurophysiological examination was performed in 64% of patients and 67% of them had AMAN. AMAN was associated with C. jejuni infection. In this study, 21% of patients were lost to follow-up and in the remaining 11% died and 29% had poor outcome at 6 months (Islam et al., 2010). A large multicentric study also reported death in 11% and poor recovery in 16% after a mean 309 days of follow-up. Age, antecedent gastroenteritis, axonopathy, the latency to nadir, and duration of active disease adversely affected the clinical recovery (Italian Guillain-Barre Study Group, 1996). We have not evaluated C. jejuni infection and anti-ganglioside 41

antibodies. These tests were not performed because of cost and lack of impact on the diagnosis or management. In northern India, C. jejuni infection has been reported in 30% of patients with GBS and prevalence in volunteers is 8% (Sinha et al., 2007). There was a significant seasonal trend of GBS subtype in our study; AMAN was common in summer and AIDP in the rainy season. The seasonal clustering of AMAN and AIDP has been reported by other investigators as well (Paradiso et al., 1999; Ogawara et al., 2000; Chroni et al., 2004; Sharma et al., 2011). GBS has a bimodal distribution, commonest in young adults and in elderly (Hughes and Rees, 1997). Our results revealed the highest frequency of GBS in 20 40 years of age, which may be due to referral bias as ours is mainly an adult neurology center. AMAN is more common in children compared to adults (Paradiso et al., 1999; Ogawara et al., 2000; Sharma et al., 2011). In our study, 21.2% of children had AMAN compared to 10.7% in adults. Although lower frequency of cranial nerve palsy has been reported in AMAN, in our study both AMAN and AIDP had similar frequency of cranial nerve palsy (Visser et al., 1995; Paradiso et al., 1999). Limb weakness was more severe in AMAN compared to AIDP. Areflexia/hyporeflexia is the important component of established diagnostic clinical criteria of GBS (Asbury and Cornblath, 1990). There is an increasing number of reports of GBS patients with brisk or retained deep tendon reflexes (DTR) (Kuwabara et al., 2002; Baheti et al., 2010; Yuki et al., 2012). In our experience, 1.2% of patients with GBS had brisk DTR at the time of hospital admission. In our earlier study on motor-evoked potentials in 30 patients with GBS, central motor conduction time was markedly slowed in two patients, suggesting the possibility of coexistent central demyelination in some patients (Kalita et al., 2001). Autopsy study of GBS also revealed central demyelination (Maier et al., 1997). The reported predictors of poor prognosis of GBS are age above 40 years, lower MRC sum score at admission, higher GBS disability score at 2 weeks, preceding diarrheal illness, need of mechanical ventilation, facial and bulbar palsy, conduction block >44% at common peroneal nerve, inexcitable motor nerves, and low CMAP amplitude (20% of lower limit of normal) (Rajabally and Uncini, 2012). In our study, 3-month poor outcome was related to age (>50 years), short interval between onset and admission, limb power (< grade 3), cranial nerve palsy, generalized areflexia, dysautonomia, peak disability, ventilator requirement, and inexcitable motor nerves on univariate analysis. On multivariate analysis, peak disability, dysautonomia, and inexcitable motor nerves were independent predictors of poor recovery at 3 months. The limitations of this study are short follow-up and lack of anti-ganglioside antibodies and C. jejuni serology correlation. 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