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Young Ninja Group (ages 3-5)

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Frank Titskey
Frank Titskey

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The Zika virus outbreaks brought to light the lack of globally applicable guidelines for the diagnosis and management of GBS. Such guidelines are necessary because the diagnosis of GBS can be challenging owing to heterogeneity in clinical presentation, an extensive differential diagnosis, and the lack of highly sensitive and specific diagnostic tools or biomarkers. Guidance for the treatment and care of patients with GBS is also needed because disease progression can vary greatly between patients, which complicates an entirely prescriptive approach to management. In addition, treatment options are limited and costly, and many patients experience residual disability and complaints that can be difficult to manage.

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Availability of globally applicable clinical guidelines for GBS is especially important as new outbreaks of pathogens that trigger GBS are likely to occur in the future. To generate this globally applicable clinical guideline for GBS, the ten most important steps in the management of GBS, covering diagnosis, treatment, monitoring, prognosis and long-term management, were identified by a group of international experts on GBS (Fig. 1). For each step, recommendations were provided on the basis of evidence from the literature and/or expert opinion, and consensus was sought for each recommendation to finalize the guideline. These recommendations are intended to assist providers in clinical decision-making; however, the use of the information in this article is voluntary. The authors assume no responsibility for any injury or damage to persons or property arising out of or related to any use of this information, or for any errors or omissions.

Following the outbreak of Zika virus and its association with an increase in the incidence of GBS, the European Union-funded Zika Preparedness Latin American Network (ZikaPLAN) was established22. Our new guideline was initially prepared by participants of the ZikaPLAN network, comprising experts on GBS from the Netherlands (S.E.L., M.R.M. and B.C.J.), Brazil (F.d.A.A.G. and M.E.D.) and the United Kingdom (H.J.W.). These members brought specific clinical and research expertise to the guideline from their leading roles in large international projects on GBS (such as the International GBS Outcome Study (IGOS)), along with direct experience in managing the large increases in GBS cases in Zika virus-affected regions of Latin America23. To develop the preliminary guidelines, a series of in-person meetings were held between lead authors on the writing committee (S.E.L., M.R.M., B.C.J. and H.J.W.), along with smaller individual meetings with colleagues in Latin America (S.E.L., F.d.A.A.G. and M.E.D.) and continuous e-mail correspondence to review drafts and receive input. On the basis of their expert opinion and through consensus, this group identified ten of the most important steps in the diagnosis and management of GBS.

In consideration of the global variation in healthcare context and variants of GBS, this first draft was subsequently reviewed by an international group of experts on GBS from Argentina (R.R.), Australia (E.M.Y.), Bangladesh (B.I.), Brazil (M.L.B.F. and C.S.), China (Y.W.), Colombia (C.A.P.), Japan (S.K.), Malaysia (N.S.), the Netherlands (P.A.v.D.), Singapore (T.U.), South Africa (K.B.), the United States (D.R.C. and J.J.S.) and the United Kingdom (R.A.C.H). In total, seven rounds of review were held to reach a consensus. To consider the perspective of patients with GBS on the management of the disease, the GBS/CIDP Foundation International, a non-profit organization that provides support, education, research funding and advocacy to patients with GBS or chronic inflammatory demyelinating polyneuropathy (CIDP) and their families, reviewed the manuscript and provided comment during the development of the guideline.

In the absence of sufficiently sensitive and specific disease biomarkers, the diagnosis of GBS is based on clinical history and examination, and is supported by ancillary investigations such as CSF examination and electrodiagnostic studies. The two most commonly used sets of diagnostic criteria for GBS were developed by the National Institute of Neurological Disorders and Stroke (NINDS) in 1978 (revised in 1990)2,3 (Box 1) and the Brighton Collaboration in 2011 (ref4) (Supplementary Table 1). Both sets of criteria were designed to investigate the epidemiological association between GBS and vaccinations but have since been used in other clinical studies and trials. We consider the NINDS criteria to be more suited to the clinician as they present the clinical features of typical and atypical forms of GBS, although the criteria from the Brighton Collaboration are also important, widely used, and can help the clinician to classify cases with (typical) GBS or MFS according to diagnostic certainty. Various differential diagnoses must also be kept in mind when GBS is suspected, and some symptoms should raise suspicion of alternative diagnoses (Boxes 1 and 2). The role of ancillary investigations in confirming a GBS diagnosis is described in more detail in the following section.

Laboratory testing is guided by the differential diagnosis in individual patients, but in general all patients with suspected GBS will have complete blood counts and blood tests for glucose, electrolytes, kidney function and liver enzymes. Results of these tests can be used to exclude other causes of acute flaccid paralysis, such as infections or metabolic or electrolyte dysfunctions (Box 2). Further specific tests may be carried out with the aim of excluding other diseases that can mimic GBS (Box 2). Testing for preceding infections does not usually contribute to the diagnosis of GBS, but can provide important epidemiological information during outbreaks of infectious diseases, as was seen in previous outbreaks of Zika virus and C. jejuni infection19,52. The diagnostic value of measuring serum levels of anti-ganglioside antibodies is limited and assay-dependent. A positive test result can be helpful, especially when the diagnosis is in doubt, but a negative test result does not rule out GBS53. Anti-GQ1b antibodies are found in up to 90% of patients with MFS17,54 and therefore have greater diagnostic value in patients with suspected MFS than in patients with classic GBS or other variants. When GBS is suspected, we advise not to wait for antibody test results before starting treatment.

MRI is not part of the routine diagnostic evaluation of GBS, but can be helpful, particularly for excluding differential diagnoses such as brainstem infection, stroke, spinal cord or anterior horn cell inflammation, nerve root compression or leptomeningeal malignancy (Box 2). The presence of nerve root enhancement on gadolinium-enhanced MRI is a nonspecific but sensitive feature of GBS65 and can support a GBS diagnosis, especially in young children, in whom both clinical and electrophysiological assessment can be challenging66. In light of recent outbreaks of acute flaccid myelitis in young children, the clinical presentation of which can mimic GBS, the potential use of MRI to distinguish between these two diagnoses should be given special attention67,68. However, clinicians should be mindful that nerve root enhancement can be found in a minority of individuals with acute flaccid myelitis69.

A new potential diagnostic tool in GBS is ultrasound imaging of the peripheral nerves, which has revealed enlarged cervical nerve roots early in the disease course, indicating the importance of spinal root inflammation as an early pathological mechanism70,71. This technique might, therefore, help establish a diagnosis of GBS early in the disease course, although further validation is required.

Complications in GBS can cause severe morbidity and death95. Some of these complications, including pressure ulcers, hospital-acquired infections (for example, pneumonia or urinary tract infections) and deep vein thrombosis, can occur in any hospitalized bed-bound patient, and standard-practice preventive measures and treatment are recommended. Other complications are more specific to GBS, for example, the inability to swallow safely in patients with bulbar palsy; corneal ulceration in patients with facial palsy; and limb contractures, ossification and pressure palsies in patients with limb weakness (Table 2). Pain, hallucinations, anxiety and depression are also frequent in patients with GBS, and caregivers should specifically ask patients whether they are experiencing these symptoms, especially if patients have limited communication abilities and/or are in the ICU. Recognition and adequate treatment of psychological symptoms and pain at an early stage is important because these symptoms can have a major impact on the wellbeing of patients. Caregivers should also be aware that patients with GBS, even those with complete paralysis, usually have intact consciousness, vision and hearing. It is important, therefore, to be mindful of what is said at the bedside, and to explain the nature of procedures to patients to reduce anxiety. Adequate management of complications is best undertaken by a multidisciplinary team, which might include nurses, physiotherapists, rehabilitation specialists, occupational therapists, speech therapists and dietitians.

GBS can be a complex disorder to diagnose and manage as the clinical presentation is heterogeneous and the prognosis varies widely between patients. Managing GBS can be especially challenging during outbreaks triggered by infectious disease, as was most recently seen during the Zika virus epidemic. In the absence of an international clinical guideline for GBS, we have developed this consensus guideline for the diagnosis and management of GBS. This guideline was developed by a team of clinical neurologists from around the world and is designed for general applicability in all clinical environments, irrespective of specialist capabilities or availability of resources. The step-by-step design was used to focus attention on the most important issues in GBS and to make the guideline easy to use in clinical practice. 041b061a72


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