Paraparetic Guillain-Barré syndrome

Paraparetic Guillain-Barré syndrome Bianca van den Berg, MD Christiaan Fokke, MD Judith Drenthen, MD Pieter A. van Doorn, MD, PhD Bart C. Jacobs, MD, PhD Correspondence to Dr. Jacobs: b.jacobs@erasmusmc.nl ABSTRACT Objective: To define the clinical and diagnostic characteristics of paraparetic Guillain-Barré syndrome (GBS) with weakness restricted to the legs, compared with the classic quadriparetic GBS. Methods: Prospectively collected data from a cohort of 490 patients with GBS, previously involved in therapeutic or clinical studies, were used to define the demography, clinical presentation, diagnostic investigations, and clinical course in patients with paraparesis during a 6-month follow-up. Results: Forty patients (8%) presented with a paraparesis without weakness of arms and hands. In 29 patients (73%), normal strength of upper extremities persisted during the follow-up period. Patients with paraparesis compared to patients with quadriparesis had a milder form of GBS, with less frequent cranial nerve involvement and less severe leg weakness, despite the fact that the majority of these patients were unable to walk unaided. Median time between onset of weakness and study entry was 6 days (interquartile range 4 11 days) for patients with paraparesis compared with 5 days (interquartile range 3 8 days) for patients with quadriparesis (p 5 0.031). Fifty percent of patients with paraparesis presented with arm sensory deficits and 73% had reduced or absent arm reflexes. Nerve conduction studies demonstrated arm nerve involvement in 89% of these patients. At 6 months of follow-up, 98% of patients with paraparesis were able to walk unaided compared with 81% of the patients with quadriparesis (p 5 0.008). There was no association between paraparesis and age, sex, or preceding infections. Conclusions: Paraparesis is an atypical clinical presentation or subform of GBS in which the diagnosis is usually supported by the presence of sensory deficits, reduced reflexes, or abnormal nerve conduction of the arms. Neurology 2014;82:1984 1989 GLOSSARY GBS 5 Guillain-Barré syndrome; Ig 5 immunoglobulin; MRC 5 Medical Research Council; NCS 5 nerve conduction study. Guillain-Barré syndrome (GBS) is a medical emergency requiring early diagnosis for accurate monitoring and treatment. 1,2 The diagnosis of GBS is largely based on a set of clinical characteristics, especially the presence of a rapidly progressive flaccid limb weakness and reduced reflexes, usually in combination with cranial or sensory nerve deficits. 3,4 In the majority of cases with classic quadriparesis, the diagnosis is straightforward. However, GBS is a clinically heterogeneous neuropathy and variant forms have been described that differ from the typical presentation. 5 10 Examples are the Miller Fisher syndrome, the pharyngeal-cervical-brachial variant, and the pure motor variant of GBS. 5 11 In patients with a variant or atypical form of GBS, the diagnosis can be difficult and delayed. Early diagnosis is important in these atypical cases, because patients with these variants may progress to full-blown GBS with respiratory failure and autonomic dysfunction. 5,8 Paraparetic forms of GBS have been described before, but only in smaller case series and without comparison with quadriparetic GBS. 12 14 Thereislittleawarenessof theexistenceofthisvariant,whichmaycauseaconsiderabledelayindiagnosis.theaimofthe current study was to identify the frequency of paraparetic GBS and to describe the clinical From the Departments of Neurology (B.v.d.B., C.F., J.D., P.A.v.D., B.C.J.), Immunology (C.F., B.C.J.), and Clinical Neurophysiology (J.D.), Erasmus MC, University Medical Centre Rotterdam; and Department of Neurology (C.F.), Gelre Hospitals Apeldoorn, the Netherlands. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. 1984 2014 American Academy of Neurology

presentation and course of these patients in detail. In addition, we aim to provide a strategy for early and accurate diagnosis in these patients. METHODS In this study, we reviewed prospectively collected data from 567 patients with GBS included in 4 studies performed by the Dutch GBS Study Group. These patients with GBS previously participated in 2 randomized controlled trials, 1 pilot study, and 1 observational study. 15 18 All patients fulfill the diagnostic criteria of GBS. 3 In the 2 randomized controlled trials and the pilot study, patients were included if onset of weakness was less than 2 weeks previous to enrollment and if the patient was unable to walk unaided. 15,17,18 In the observational study, patients with a relatively mild form of GBS, who were still able to walk unaided, were also included. 16 All patients had a routine diagnostic workup to exclude other diagnoses and to confirm GBS. The follow-up duration was at least 6 months. 19 Seventy-seven patients (13.6%) were excluded, including children (n 5 32), patients with Miller Fisher syndrome (n 5 18), acute onset chronic inflammatory demyelinating polyneuropathy (n 5 10), Bickerstaff encephalitis (n 5 2), missing data about distribution of weakness at entry (n 5 4), alternative diagnosis appearing during follow-up (myelitis transversa, Sjögren syndrome, spinal disk herniation, uncertain diagnosis, sacral tumor, vasculitis) (n 5 10), and a previous episode of GBS (n 5 1). For the remaining 490 patients included in the current study, data were collected about age, sex, preceding infections, severity and distribution of weakness, sensory disturbances and reflexes in arms and legs, cranial nerve deficits, and pain. The GBS disability score, ranging from 0 (healthy) to 6 (death), was documented, with a score of 3 indicating that a patient is not able to walk 10 m without help. 20 The Medical Research Council (MRC) sum score was used to register weakness and is a sum of 6 bilateral muscles, 3 bilateral muscles in arms and 3 bilateral muscles in legs, resulting in a score ranging from 0 (quadriplegic) to 60 (normal strength). 21 Results of laboratory investigations, including infection serology and immunoglobulin (Ig)M and IgG antibodies to the gangliosides GM1, GD1a, and GQ1b, and CSF studies, nerve physiology, and neuroimaging were also collected. Paraparetic GBS was defined as weakness of both legs in combination with a normal strength in the muscle groups of the upper extremities included in the MRC sum score (shoulder abduction, elbow flexion, wrist extension) at study entry. Normal strength in hand and other arm muscles (not included in the MRC sum score) was confirmed by reviewing the discharge letter and case record forms of the patients. Patients with paraparesis were compared to patients with quadriparesis regarding clinical features, symptoms of preceding infection, and results of additional investigations, disease severity, and outcome. Standard protocol approvals, registrations, and patient consents. The studies were approved by an ethical standards committee on human experimentation, and informed consent was obtained from all patients. Statistics. SPSS statistics 20.0 (IBM Corp., Armonk, NY) was used for data analysis. A 2-sided p value,0.05 was considered to be statistically significant. The x 2 or Fisher exact test was used to compare proportions. Continuous variables were presented as medians and interquartile ranges and compared using the Mann-Whitney U test. Kaplan-Meier analysis was used to compare the clinical course of patients with paraparesis vs quadriparesis. RESULTS Forty patients with GBS (8%) had a paraparesis of the legs with no weakness in the upper extremities. Compared to patients with quadriparesis, this subgroup had a relatively mild form of GBS (table 1). Patients with paraparesis had less severe leg weakness compared to patients with quadriparesis, as indicated by the higher MRC scores of the leg muscle groups in the MRC sum score. In addition, patients with paraparesis had less frequent cranial nerve involvement and respiratory failure compared to patients with quadriparesis. Patients with paraparesis in general also had a milder disability than patients with quadriparesis, as indicated by a larger proportion of patients with a lower GBS disability score, despite the fact that 36 patients (90%) with paraparesis were unable to walk independently at nadir and 1 patient (3%) died. Also, a lower proportion of patients with paraparesis vs patients with quadriparesis received treatment. Time between onset of weakness and study entry was longer in patients with paraparesis than in those with quadriparesis. There were no differences between patients with paraparesis vs quadriparesis in age, sex, type of antecedent infection, findings in CSF, and electrophysiologic subtype (table 1). More details of the specific diagnostic features of patients with paraparesis are provided in table 2. Most patients with paraparesis had a diffuse distribution of leg weakness, but in some patients, only the proximal or distal muscles were affected. Normal strength of the arms persisted during follow-up in 29 (73%) of these patients. Neurologic examination of the arms at entry demonstrated sensory deficits in 50% and reduced or absent reflexes in 73% of patients. A sensory level was not reported in any of the patients with paraparesis; 14% had symptoms of bladder dysfunction. Nerve conduction studies (NCS), performed at a median of 16 days (interquartile range 8 25 days) after onset of weakness, demonstrated abnormalities of arm nerves in 89% of patients with paraparesis. Decreased compound muscle action potential amplitudes in one of the arm nerves was the most common finding, together with abnormalities in needle EMG, followed by a prolonged distal motor latency and abnormalities in F-wave latency. However, 57% (20/35) showed fewer than 3 of these abnormalities in NCS of the arms. The cell count in CSF was 0 5 cells/ml in 79%, 5 10 cells/ml in 5%, and 10 50 cells/ml in 16% of patients with paraparesis. This distribution in cell count was not significantly different from the distribution in patients with quadriparesis. Data from imaging studies were available from 12 (30%) of the 40 patients with paraparesis, and in none were abnormalities found that could indicate a diagnosis other than GBS. One of the patients with paraparesis had anti-gm1 IgM antibodies, one other patient was Neurology 82 June 3, 2014 1985

Table 1 Clinical characteristics of patients with paraparetic vs quadriparetic GBS Patient characteristic Paraparetic (n 5 40) Quadriparetic (n 5 450) p Value Males 63 (25) 55 (248) 0.37 Age, y 51 (38 69) 53 (36 66) 0.90 Neurologic symptoms at entry Cranial nerve involvement 15 (6) 38 (171/449) 0.004 Sensory deficits upper or lower extremities 75 (27/36) 66 (292/441) 0.28 Pain 52 (229/441) 71 (27/38) 0.023 MRC score 6 arm muscles a 30 24 (18 25),0.001 MRC score 6 leg muscles b 24 (22 26) 20 (15 24),0.001 GBS disability score c 1 and 2 13 (5/39) 5 (23/450) 0.062 3 56 (22/39) 21 (94/450),0.001 4 31 (12/39) 64 (286/450),0.001 5 0 (0/39) 10 (47/450) 0.024 Decreased reflexes in arms 73 (24/33) 89 (322/361) 0.01 Decreased reflexes in legs 100 (33/33) 97 (366/376) 1.0 Neurologic symptoms at nadir MRC sum score 54 (48 56) 38 (22 46),0.001 GBS disability score c 1 and 2 8 (3/40) 4 (17/450) 0.22 3 45 (18/40) 14 (62/450),0.001 4 43 (17/40) 52 (232/450) 0.27 5 3 (1/40) 28 (125/450),0.001 6 3 (1/40) 3 (14/450) 1.0 Cranial nerve involvement 32 (12/38) 54 (243/448) 0.007 Additional investigations Elevated CSF protein, >0.58 g/l 73 (29/40) 64 (276/431) 0.28 Nerve conduction studies 0.65 Demyelinating 44 (15/34) 49 (197/403) Axonal 6 (2/34) 6 (25/403) Equivocal 50 (17/34) 40 (162/403) Inexitable 0 (0/34) 4 (15/403) Normal 0 (0/34) 1 (4/403) Clinical course Days from onset of weakness to study entry 6(4 11) 5 (3 8) 0.031 Duration of progressive phase d 10 (5 13) 8 (5 14) 0.93 Specific treatment, IVIg or PE 88 (35/40) 97 (436/450) 0.014 Walking unaided at 6 mo 98 (39/40) 81 (360/446) 0.008 Abbreviations: GBS 5 Guillain-Barré syndrome; IVIg 5 IV immunoglobulin; MRC 5 Medical Research Council; PE 5 plasma exchange. Data are shown as medians (interquartile ranges) or percentages (number of patients). a MRC sum score of 3 bilateral arm muscle groups: upper arm abductors, elbow flexors, and wrist extensors on both sides. b MRC sum score of 3 bilateral leg muscles: hip flexors, knee extensors, and foot dorsal flexors on both sides. c GBS disability score: 0 5 healthy; 1 5 minor symptoms and capable of running; 2 5 able to walk 10 m or more without assistance but unable to run; 3 5 able to walk 10 m across an open space with help; 4 5 bedridden or wheelchair-bound; 5 5 requiring assisted ventilation for at least part of the day; and 6 5 death. d Number of days between onset of weakness and nadir. 1986 Neurology 82 June 3, 2014

Table 2 Clinical features and additional investigations of patients with paraparetic GBS Patient characteristic Paraparetic (n 5 40) Neurologic symptoms at entry Distribution of weakness Hip flexion 4(4 4) Knee extension 4(4 5) Foot dorsiflexion 4(4 5) Reflexes arms Areflexia 39 (13/33) Hyporeflexia 33 (11/33) Normoreflexia 27 (9/33) Sensory deficits arms a 50 (19/38) Bladder dysfunction 14 (2/12) Sensory level 0 (0/28) Neurologic symptoms during follow-up Weakness arms 28 (11/40) Additional investigations Nerve conduction study abnormalities in arms 89 (31/35) Decreased CMAP amplitude 61 (20/33) Prolonged DML 54 (19/35) Prolonged MCV 26 (9/35) Decreased SNAP 46 (13/28) Abnormalities in F-wave latency 53 (10/19) Abnormalities in myogram 61 (11/18) Abbreviations: CMAP 5 compound muscle action potential (mv); DML 5 distal motor latency (ms); GBS 5 Guillain-Barré syndrome; MCV 5 motor conduction velocity (m/s); SNAP 5 sensory nerve action potential (mv). Data are shown as medians (interquartile ranges) or percentages (number of patients). a Sensory deficits arms at neurologic examination. anti-gm1 IgG positive, and one other patient was anti-gd1a IgM positive and anti-gq1b IgM positive. During follow-up, no alternative diagnosis was made despite routine diagnostic workup. Only one patient (3%) in the current cohort had a paraparesis without involvement of the cranial nerves or weakness, sensory deficits, reduced reflexes, or abnormal NCS of the arms. This patient was admitted after 3 weeks of slowly progressive weakness of both legs. Neurologic examination revealed a mild symmetrical weakness of the proximal and distal muscles and areflexia of both legs. CSF showed no cell count and a protein level of 0.80 g/l. MRI of the lumbar spine showed a relative spinal stenosis at L4-5, which could not explain the more extensive weakness in the legs. NCS was compatible with a mild demyelinating neuropathy of the legs. The patient had difficulty walking and was treated with one course of IVIg,afterwhichhefullyrecovered. Patients with paraparesis in general had a better outcome than patients with quadriparesis. After a follow-up of 6 months, 98% of patients with paraparesis were able to walk unaided, compared with 81% of patients with quadriparesis (p 5 0.008). The clinical course of patients with paraparetic vs quadriparetic GBS is shown in the figure. Five patients with paraparesis did not receive specific treatment, but they all reached the level of independent walking. One patient with paraparesis died unexpectedly at 90 days after onset of weakness at a rehabilitation center, probably of a cardiovascular complication. This patient had no arm weakness or respiratory failure and regained the ability to walk. DISCUSSION In the current study, 8% of patients with GBS presented with a paraparesis in absence of weakness of the arms. These patients had symmetrical weakness and reduced reflexes of the legs, and as such fulfilled the current diagnostic criteria for GBS. 3 In a proportion of patients, the diagnosis of GBS was further supported by the presence at study entry of cranial nerve involvement (15%), sensory deficits of the arms (50%), or areflexia of the arms (39%). During the progressive phase, only 28% of patients with paraparesis developed additional weakness of the arms. All patients with paraparesis showed a typical monophasic clinical course with improvement in the following weeks. The diagnosis of GBS was further supported by the findings in CSF, and all patients with paraparesis had an abnormal NCS. Routine diagnostic workup in these patients revealed no other cause for the paraparesis, even after a follow-up of 6 months. The findings in these patients therefore demonstrate that paraparesis can be a first clinical presentation or persistent subform in a proportion of patients with GBS. Compared with patients with typical quadriparetic GBS, the patients with paraparetic GBS were relatively mildly affected, although the majority of patients with paraparesis were unable to walk independently at nadir. Patients with paraparetic vs quadriparetic GBS had less frequent cranial nerve deficits and respiratory failure and less severe weakness of the legs. In our cohort, 88% of patients with paraparesis were treated with IVIg or plasma exchange, usually because they were unable to walk independently. After treatment, these patients showed a faster and more complete recovery than the patients with quadriparesis. The relatively good outcome of patients with paraparesis is probably influenced by the mild severity, which is one of the determinants for good recovery. 22 Together, these findings indicate that paraparetic GBS is a mild or regional form of GBS in which the motor nerves of Neurology 82 June 3, 2014 1987

Figure Time to reach the ability to walk unaided in patients with paraparetic vs quadriparetic GBS Kaplan-Meier analysis was conducted in a total of 440 patients with GBS who had detailed information available on clinical course during a follow-up of 6 months. GBS 5 Guillain-Barré syndrome. the legs are most severely affected, but the disease rarely progresses to respiratory failure and quadriparesis. A similar situation occurs in the Miller Fisher syndrome, which in some patients may progress to full-blown Miller Fisher syndrome GBS overlap syndrome with quadriparesis orrespiratoryfailure. At present, it is unknown which microbial or host factors determine the progression and extent of peripheral nerve damage. Genetic host factors may influence the disease severity, as was indicated by the functional polymorphisms in the mannose binding lectin 2 gene, which influences the level and activity of complement in blood and is related to the extent of weakness. 23 There are several limitations of our study. First, the investigated patient cohort may be biased toward typical quadriparetic cases of GBS to certify the inclusion criteria of the therapeutic studies, resulting in an underestimation of the actual frequency of paraparetic GBS. Second, not all patients with paraparetic GBS had imaging to exclude other disorders, especially in patients from the older trials when MRI was not routinely available in the clinic. However, 98% of the patients with paraparesis had either sensory disturbances of the arms or either hypo- or areflexia of the arms, or abnormalities at NCS of the upper extremity that confirmed the diagnosis of GBS, which made additional imaging unnecessary. Only one patient had a paraparesis without involvement of the upper extremities and a lumbar MRI was performed to exclude other diagnoses. None of these patients received another diagnosis during the follow-up and all showed a monophasic course with good recovery. Early recognition of GBS in clinical practice is crucial for accurate monitoring and treatment in the initial progressive phase of disease. Previous studies indicate that the diagnosis may be delayed in atypical clinical presentations, such as in young children. 24 The clinical relevance of the current study is that GBS should be among the differential diagnoses of patients with rapidly progressive symmetrical paraparesis with reduced reflexes. Rapidly progressive flaccid symmetrical paraparesis of the legs may be caused by a spectrum of other causes, including transverse myelitis, spinal cord compression, leptomeningeal malignancy, lymphoma, and infectious or autoimmune caudal equina neuritis. 2 The atypical presentation and differential diagnosis may have caused a delay in diagnosis as indicated by the longer duration between onset of weakness and study entry in patients with paraparesis compared to those with quadriparesis, although paraparetic GBS may also have had a less rapid initial disease progression. Our study indicates that there are important diagnostic clues in the early phase of paraparetic GBS. First, most patients had additional symptoms in neurologic examination indicating GBS, being cranial nerve involvement or sensory deficits or hypoor areflexia of the arms. In addition, involvement of the nerves in the upper extremities was further substantiated by the findings in the NCS. Examination of CSF is important, more to exclude infectious causes related to pleocytosis than to confirm the high protein level that is frequently absent in GBS, especially when examined early in the onset of GBS. 19 If there is a sensory level at neurologic examination or prominent or persistent urinary bladder dysfunction, this should cast doubt on the diagnosis of GBS, and additional imaging studies may be required to exclude the presence of spinal cord or cauda equina compression. In addition, in 95% of cases of GBS, MRI with gadolinium may show enhancement of the cauda equina nerve roots, and in the acute phase has a sensitivity of 83% for the diagnosis of GBS. 25 In conclusion, paraparesis is an infrequent clinical presentation or subform of GBS, but involvement of cranial and arm nerves should raise the suspicion of the accurate diagnosis. AUTHOR CONTRIBUTIONS B. van den Berg contributed to the conceptualization of the study, performed the analysis and interpretation of the data, and drafting and revising of the manuscript. C. Fokke contributed to the conduct and the analysis of the study, interpretation of the data, and revisions of the manuscript. J. Drenthen contributed to the conduct of the study, interpretation of the data, and revisions of the manuscript. Prof. P.A. van Doorn contributed to organizing the clinical studies that provided the data for the study, interpretation of the data, and revising the manuscript. Dr. B.C. Jacobs developed the study design, contributed to the conceptualization of the study, performed the analysis and interpretation of the data, and drafting and revising of the manuscript. 1988 Neurology 82 June 3, 2014

STUDY FUNDING No targeted funding reported. DISCLOSURE B. van den Berg, C. Fokke, and J. Drenthen report no disclosures relevant to the manuscript. P. van Doorn receives research support from the Prinses Beatrix Spierfonds, the GBS-CIDP Foundation International, Baxter Biopharmaceutics, Grifols, and Sanquin Plasma Products. B. Jacobs receives research support from the Netherlands Organization for Health Research and Development, Erasmus MC, Prinses Beatrix Spierfonds, and GBS-CIDP Foundation International, and travel support from Baxter Biopharmaceutics. Go to Neurology.org for full disclosures. Received December 2, 2013. Accepted in final form February 28, 2014. REFERENCES 1. Hughes RA, Wijdicks EF, Benson E, et al. Supportive care for patients with Guillain-Barré syndrome. Arch Neurol 2005;62:1194 1198. 2. van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol 2008;7:939 950. 3. Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barré syndrome. Ann Neurol 1990;27(suppl):S21 S24. 4. Sejvar JJ, Kohl KS, Gidudu J, et al. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 2011;29:599 612. 5. Mori M, Kuwabara S, Yuki N. Fisher syndrome: clinical features, immunopathogenesis and management. Expert Rev Neurother 2012;12:39 51. 6. Van der Meche FG, Van Doorn PA, Meulstee J, Jennekens FG; GBS-Consensus Group of the Dutch Neuromuscular Research Support Centre. Diagnostic and classification criteria for the Guillain-Barré syndrome. Eur Neurol 2001;45:133 139. 7. Visser LH, Van der Meche FG, Van Doorn PA, et al. Guillain-Barré syndrome without sensory loss (acute motor neuropathy): a subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barré Study Group. Brain 1995;118:841 847. 8. Wakerley BR, Yuki N. Pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 2014;85:339 344. 9. Winer JB. Guillain-Barré syndrome: clinical variants and their pathogenesis. J Neuroimmunol 2011;231:70 72. 10. Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med 2012;366:2294 2304. 11. Kuwabara S, Yuki N. Axonal Guillain-Barré syndrome: concepts and controversies. Lancet Neurol 2013;12: 1180 1188. 12. Ropper AH. Miller Fisher syndrome and other acute variants of Guillain-Barré syndrome. Baillieres Clin Neurol 1994;3:95 106. 13. Carpo M, Pedotti R, Allaria S, et al. Clinical presentation and outcome of Guillain-Barré and related syndromes in relation to anti-ganglioside antibodies. J Neurol Sci 1999; 168:78 84. 14. Ropper AH. The Guillain-Barré syndrome. N Engl J Med 1992;326:1130 1136. 15. Treatment of Guillain-Barré syndrome with high-dose immune globulins combined with methylprednisolone: a pilot study. The Dutch Guillain-Barré Study Group. Ann Neurol 1994;35:749 752. 16. Ruts L, Drenthen J, Jacobs BC, van Doorn PA; Dutch GBS Study Group. Distinguishing acute-onset CIDP from fluctuating Guillain-Barré syndrome: a prospective study. Neurology 2010;74:1680 1686. 17. van der Meche FG, Schmitz PI. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. Dutch Guillain-Barré Study Group. N Engl J Med 1992;326:1123 1129. 18. van Koningsveld R, Schmitz PI, Meche FG, et al. Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome: randomised trial. Lancet 2004;363:192 196. 19. Fokke C, van den Berg B, Drenthen J, Walgaard C, van Doorn PA, Jacobs BC. Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria. Brain 2014;137:33 43. 20. Hughes RA, Newsom-Davis JM, Perkin GD, Pierce JM. Controlled trial prednisolone in acute polyneuropathy. Lancet 1978;2:750 753. 21. Kleyweg RP, van der Meche FG, Schmitz PI. Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome. Muscle Nerve 1991;14:1103 1109. 22. Walgaard C, Lingsma HF, Ruts L, van Doorn PA, Steyerberg EW, Jacobs BC. Early recognition of poor prognosis in Guillain-Barré syndrome. Neurology 2011; 76:968 975. 23. Geleijns K, Roos A, Houwing-Duistermaat JJ, et al. Mannosebinding lectin contributes to the severity of Guillain-Barré syndrome. J Immunol 2006;177:4211 4217. 24. Roodbol J, de Wit MC, Walgaard C, de Hoog M, Catsman-Berrevoets CE, Jacobs BC. Recognizing Guillain-Barré syndrome in preschool children. Neurology 2011;76:807 810. 25. Gorson KC, Ropper AH, Muriello MA, Blair R. Prospective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain-Barré syndrome. Neurology 1996;47: 813 817. Neurology 82 June 3, 2014 1989