Guillain-Barré syndrome in adults: Treatment and prognosis

INTRODUCTION — The acute immune-mediated polyneuropathies are classified under the eponym Guillain-Barré syndrome (GBS), after the authors of early descriptions of the disease. GBS is an acute monophasic paralyzing illness usually provoked by a preceding infection.

The treatment and prognosis of GBS in adults will be discussed here. Other aspects of GBS are discussed separately:

●(See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis".)

●(See "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis".)

●(See "Guillain-Barré syndrome in children: Treatment and prognosis".)

TRIAGE — Patients with GBS should be admitted to an inpatient setting for serial hemodynamic and neurologic monitoring and to guide therapy.

Initial clinical assessments — Baseline neurologic, respiratory, and hemodynamic evaluations should be performed at admission. In addition, patients should be assessed and monitored for bowel and bladder dysfunction.

●Neurologic monitoring – Performance on baseline neurologic examination is used to assess for disease progression and can also be incorporated into clinical scales used to predict disease severity and the risk for clinical deterioration. (See 'Neurologic status' below and 'Indications for ICU level care' below.)

The neurologic examination tailored to patients with acute GBS includes:

•Muscle strength testing in all four limbs – This includes shoulder abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and foot dorsiflexors to help calculate the Medical Research Council (MRC) sum score range 0 (quadriplegic) to 60 (normal) (table 1) [1]. (See 'Indications for ICU level care' below.)

•Facial/bulbar/neck strength assessment in the facial muscles and the neck flexors and extensors – Progressive weakness in these muscle groups indicates a worse prognosis and a greater possibility of the need for mechanical ventilation. (See 'Indications for ICU level care' below.)

•Formal speech and swallowing assessment – A speech therapy consultation can help to assess swallowing function and to determine what dietary modifications or restrictions may be necessary. This should also include an assessment of the ability to cough to provide insight into bulbar weakness and the potential for aspiration and respiratory complications. Weakness in these muscle groups indicates a higher likelihood of the need for mechanical ventilation and a worse prognosis. (See 'Indications for ICU level care' below.)

●Ventilation status – Respiratory rate, oxygen saturation, forced vital capacity (FVC), maximal inspiratory pressure (also known as negative inspiratory force), and maximal expiratory pressure should be instituted in all patients [2]. Serial monitoring is indicated to assess for progressive worsening and the need for mechanical ventilation. (See 'Indications for ICU level care' below and 'Ventilatory status' below.)

●Hemodynamic monitoring – Close monitoring of heart rate and rhythm, blood pressure, and fluid status is essential to the management of patients with GBS [3]. (See 'Indications for ICU level care' below and 'Cardiovascular and autonomic status' below.)

Indications for ICU level care — An early determination should be made to identify which patients warrant admission to an intensive care unit (ICU). Such patients include those with impending respiratory failure, severe or rapidly progressive weakness, or autonomic instability [4-8].

●Impending respiratory failure – Patients with signs of imminent respiratory failure require ICU admission and urgent ventilatory support. ICU admission is also warranted for other patients with a rapid decline in respiratory function (>30 percent in 24 hours) who do not have overt signs of imminent respiratory failure. This setting provides monitoring to allow for an elective intubation if necessary and can decrease the need for emergent intubation [8].

Clinical signs of respiratory failure include obvious shortness of breath while speaking or at rest, use of accessory muscles of breathing, inability to count to 15 in one breath, increased respiratory rate with tachycardia or abnormal arterial blood gases, and FVC <15 to 20 mL/kg or <1L.

Performance on pulmonary function tests can help identify patients with an indication for intubation due to respiratory failure. (See 'Ventilatory status' below.)

●Severe weakness – We admit (or transfer) patients to an ICU setting who present with weakness that is severe or rapidly progressive and are at high risk for respiratory failure. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) scale is used to predict the risk of respiratory failure within the first week of admission [5]. The EGRIS scale is scored from 0 to 7 and incorporates the time interval from onset of weakness to hospital admission, the presence of bulbar or facial weakness, and the MRC sum score (table 1). Patients who achieve a score 0 to 2 are at low risk for respiratory failure (4 percent), those with a score 3 to 4 are at intermediate risk (24 percent), and those with a score 5 to 7 are at high risk (65 percent).

●Autonomic instability – Patients with cardiac arrhythmias or labile blood pressure indicative of autonomic dysfunction also warrant ICU admission [9]. (See 'Cardiovascular and autonomic status' below.)

Less severely affected patients can be managed in intermediate care units, and mildly affected patients who are not in the acute (progressive) phase can be managed on the general ward unit. However, continued monitoring of neurologic, respiratory, and hemodynamic status is necessary until patients are in the plateau phase (symptoms stable for >72 hours) since patients with GBS can deteriorate quickly.

SUPPORTIVE MANAGEMENT AND MONITORING — All patients with GBS should be monitored for deterioration with supportive care to address symptoms or their progression (algorithm 1).

Expected timeframe of disease progression — GBS is an acute monophasic polyneuropathy that evolves to a nadir typically within four weeks before improving. The timeframe of GBS was illustrated by a retrospective series of 162 patients who were evaluated in the era before the advent of disease-modifying treatment [10]. Nearly 75 percent showed continued progression for up to two weeks, followed by a plateau phase of two to four weeks, and then recovery of function. Most patients (67 percent) were recovering by four weeks after onset.

For patients who worsen beyond two to four weeks, diagnostic reevaluation is indicated. (See 'Approach to patients who relapse or worsen' below.)

Up to 30 percent of patients develop neuromuscular respiratory failure requiring mechanical ventilation [2]. Autonomic dysfunction may occur in 70 percent of patients and typically requires continuous monitoring and frequent medical interventions typically performed in an intensive care unit (ICU) setting [11]. Severe autonomic dysfunction occurs in approximately 20 percent of patients, mostly (but not always) in patients who develop severe weakness and respiratory failure.

Continued monitoring is warranted if the disease is still evolving. Progression of the disease or the lack of it in the preceding 72 hours can be useful in predicting the chance of further worsening, although there are exceptions. Patients who reach the nadir rapidly may have a more severe course and warrant more aggressive treatment.

Neurologic status — Serial neurologic examinations should be performed at least daily during the acute phase for patients admitted with GBS. Progressive neurologic weakness may help identify patients at risk for respiratory failure.

More frequent neurologic evaluations (eg, every four to eight hours) are performed for those at high risk for deterioration and for those who may be rapidly worsening. (See 'Indications for ICU level care' above.)

Ventilatory status — Neuromuscular weakness leading to respiratory failure in GBS may occur rapidly. Serial assessments of respiratory status during the acute phase can help identify patients at risk for respiratory failure.

●Parameters to monitor – Monitoring of respiratory rate, oxygen saturation, forced vital capacity (FVC), maximal inspiratory pressure (also known as negative inspiratory force [NIF]), and maximal expiratory pressure (MEP) should be instituted in all patients [2].

●Monitoring frequency – Oxygen saturation and pulmonary function measurements should be monitored every two to four hours for all patients. The frequency can be reduced to every six to eight hours for patients with mild weakness who remain clinically stable for at least two to three days.

●Indication for intubation – Specific clinical features and thresholds on pulmonary function tests allow for the detection of those who may warrant intubation due to high risk for respiratory failure [7,9,12]. These include patients with shortness of breath while speaking or at rest, those using accessory respiratory muscles, those unable to count to 15 in one breath, or those with the following parameters:

•Respiratory rate sustained at >30 breaths/minute

•Oxygen saturation <92 percent

•FVC <20 mL/kg or reduction >30 percent from prior measurement

•NIF reduction below -30 cm H₂0 (eg, -25 cm H₂0)

•MEP <40 cm H₂0

•Acute hypercapnia with a PaCO₂ >50 mmHg

Bulbar dysfunction with swallowing impairment, inability to clear secretions, and other signs of muscle weakness may also indicate the need for ventilatory support [7].

In a French prospective study of 722 patients with GBS not ventilated at admission, mechanical ventilation was needed in 313 (43 percent) [13]. Predictors of respiratory failure included the inability to cough, stand, lift the head, or lift the elbows. Other predictors of mechanical ventilation included the time from symptom onset to hospital admission of <7 days and elevated of liver enzymes. For patients with at least four of these six predictors, mechanical ventilation was required in >85 percent.

●Intubation and ventilatory management – Patients with signs of impending respiratory failure should be intubated without delay. Emergency intubation can be complicated with severe and even life-threatening autonomic problems [14]. Noninvasive ventilation is not a safe option for GBS [15].

When invasive airway management becomes necessary, succinylcholine should be avoided to avoid the risk of inducing hyperkalemia [16]. The techniques and medications for rapid sequence intubation in adults are discussed separately. (See "Rapid sequence intubation in adults for emergency medicine and critical care".)

Weaning from mechanical ventilation should be guided by improvement in strength and serial pulmonary function tests (PFTs) [2]. Tracheostomy is typically performed after two weeks if PFTs do not show any significant improvement from baseline but can be deferred for another week if PFTs do show improvement [2]. Issues related to the respiratory management of patients with neuromuscular weakness are also discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation".)

Cardiovascular and autonomic status — Autonomic dysfunction is a well-recognized feature of GBS and a significant source of mortality [3,17]. Cardiovascular symptoms include paroxysmal fluctuations in blood pressure and tachy- and bradyarrhythmias as well as less frequent manifestations such as myocarditis or heart failure [18]. Sustained sinus tachycardia is the most common cardiac arrhythmia, affecting 25 to 38 percent of patients with GBS [18-21]. Additional arrhythmias and electrocardiogram (ECG) changes reported with GBS include atrial fibrillation, atrial flutter, paroxysmal tachycardia, ventricular tachycardia, elevated or depressed ST segments, flat or inverted T waves, QT interval prolongation, axis deviation, and various conduction blocks [11].

Other autonomic symptoms reported in patients with GBS include urinary retention, ileus, or loss of sweating. Paroxysmal hypertension and orthostatic hypotension may also be frequent, occurring in 24 and 19 percent of patients, respectively, while sustained hypertension occurred in 3 percent, as described in a series of 169 patients [22].

●Monitoring – Continuous telemetry monitoring and blood pressure measurements at least every four hours should be continued until patients stabilize or improve [2,23]. We repeat an ECG for cardiac symptoms or indication of an arrhythmia on telemetry. In addition, we include daily abdominal auscultation for all patients and obtain an abdominal radiograph for those who develop abdominal distention or absent bowel sounds suggesting the development of adynamic ileus.

●Management – Intraarterial monitoring should be instituted for patients with significant blood pressure fluctuations.

Hypotension is treated initially with intravenous fluids; low-dose phenylephrine 0.1 to 1.5 mcg/kg/minute may be useful if intravenous fluids alone are not effective [24]. For patients with persistent hypotension, other vasopressors may be warranted (table 2). In addition, other conditions must be excluded, such as pulmonary thromboembolism, hypoxemia, sepsis, gastrointestinal bleeding, and fluid and electrolyte disturbances [11]. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock".)

Severe hypertension (mean arterial pressure >125 mmHg) may be treated with labetalol, nicardipine, clevidipine, or nitroprusside [19,22]. Short-acting vasoactive agents may be used for treatment of hypotension and hypertension. Dosage should be carefully titrated because of the potential to overshoot the target blood pressure in the setting of possible denervation hypersensitivity [19]. (See "Drugs used for the treatment of hypertensive emergencies".)

Serious or life-threatening cardiac arrhythmias, including atrioventricular block and asystole, can occur with GBS and may require intervention with administration of atropine or cardiac pacing [18]. Other causes of cardiovascular disease should also be investigated. As an example, some drugs can provoke abnormalities of cardiac electrical conduction, including sinus arrest (eg, metoclopramide) [25]. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".)

For treating ileus, neostigmine may be effective [2]. However, neostigmine must be used cautiously because it can worsen bradycardia. Methylnaltrexone may be effective when opiates are contributing to the ileus. Severe ileus may require therapeutic colonoscopy.

Additional measures for the management of autonomic dysfunction for patients with GBS include [22]:

•Quadriplegic patients should not be left unattended in the sitting position due to the risk of orthostatic hypotension.

•Intravascular volume should be maintained.

•Drugs with hypotensive adverse effects should be avoided if possible.

•Drugs that may cause or worsen ileus or urinary retention should be minimized.

•Oral and pharyngeal suctioning should be performed with telemetry monitoring due to the risk of arrhythmia.

DVT prophylaxis — We use low molecular weight heparin and intermittent pneumatic compression or compressive stockings until patients are able to walk independently, unless a contraindication exists [2]. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)

Pain control — Pain occurs in approximately two-thirds of patients with acute GBS and those in the recovery phase. Pain in GBS may be both somatic, related to inflammation of nerves, and neuropathic, secondary to axonal degeneration. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Clinical features'.)

For short-term pain management, we use pain severity and individual patient factors to select among options. Acute medications for patients with GBS include:

●Medications to treat neuropathic pain such as gabapentin or carbamazepine [2,26]

●Simple analgesics or nonsteroidal antiinflammatory drugs (NSAIDs)

●Opioid analgesics (careful monitoring for adverse effects in the setting of autonomic denervation, particularly ileus, is required)

●Epidural morphine for severe or refractory pain [19]

For the long-term management of neuropathic pain, tricyclic antidepressants, gabapentin, carbamazepine, or pregabalin may be useful. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Pharmacologic therapy for neuropathic pain, or nociplastic or centralized pain'.)

Pregnant patients — GBS does not appear to occur with increased frequency during pregnancy, nor has uncomplicated disease been shown to affect pregnancy, labor, or delivery [27,28]. GBS is not an indication for cesarean delivery, which should be reserved for the usual obstetric indications only. Consultation with the anesthesia service is important, as these patients have some additional anesthetic issues (eg, need to avoid succinylcholine, concerns about exacerbation of neurologic deficit, autonomic instability) [27]. (See "Neuraxial analgesia for labor and delivery (including instrumental delivery)".)

IMMUNOMODULATORY THERAPY — Immunotherapy with either intravenous immune globulin (IVIG) or plasma exchange (PLEX) is effective for disease-modifying treatment in GBS (algorithm 1) [29-31].

The time to onset of recovery may be shortened by approximately 40 to 50 percent by treatment with PLEX or IVIG. In one trial of 245 patients, functional improvement among those treated with PLEX was quicker than those assigned placebo (19 versus 40 days) [32]. The median time to walking unaided in the PLEX and control groups was 53 and 85 days, respectively.

Indications for immunomodulatory therapy — For nonambulatory adult patients with GBS who are within four weeks of symptom onset, we recommend treatment with PLEX or IVIG. We suggest treating ambulatory adult patients with IVIG or PLEX if they are within four weeks of neuropathic symptom onset and not yet recovering [29]. (See 'Immunomodulatory therapy' above.)

Nevertheless, not all patients benefit from treatment, and the eventual functional outcome in some cases may not be influenced by immunotherapy [33]. We use symptom severity, duration, and examination findings to select patients who may benefit.

●Severity of symptoms – Immunotherapy should be instituted in patients who are unable to walk a distance of 10 meters independently [30,31]. Even though there is no definite evidence of efficacy, we also use immunotherapy for patients with rapidly progressive weakness (eg, loss of grip or antigravity arm strength over preceding 24 hours) and/or respiratory, bulbar, or autonomic involvement even if they do not meet this threshold [34-36].

●Duration since symptom onset – In most cases, immunotherapy should be started within four weeks of onset of symptoms. Evidence from a systemic review of clinical trial data suggests IVIG or PLEX improves outcome when started within two or four weeks of symptom onset [30,31]. In addition, we offer immunotherapy to selected patients with severe GBS symptoms that are progressing beyond four (and within eight) weeks from onset, although evidence of efficacy beyond this time frame is uncertain.

●Patients with variant forms – For most patients with variant forms of GBS for which the efficacy of immunotherapy has not been firmly established, we use symptom severity to make empiric decisions regarding acute treatment.

For patients with the Miller Fisher variant syndrome (MFS) of GBS, we reserve immunotherapy for those who have severe impairments including respiratory involvement and those whose symptoms evolve to include bulbar or limb weakness. For other stable patients with isolated ophthalmoplegia, areflexia, and ataxia of MFS, we avoid treatment because there is no evidence that immunotherapy changes outcomes. Most patients with MFS recover completely within six months with no treatment [37]. Nevertheless, clinical surveillance for all MFS patients should continue during the acute period because some of these patients can evolve over time and develop limb weakness, facial palsy, or respiratory involvement, perhaps necessitating treatment [35,38].

For patients with Bickerstaff brainstem encephalitis, we offer immunotherapy because of the severity of symptoms, despite lack of evidence of the efficacy [39,40].

Selection of agent — When both therapies are equally available and there are no contraindications for either, we prefer treating with IVIG because it is generally better tolerated and easier to administer than PLEX [31].

The choice between PLEX and IVIG is dependent on local availability and on patient preference, risk factors, and contraindications [34-36,40]. The design of clinical trials that provide evidence of efficacy of immunotherapy administered PLEX within four weeks of symptom onset and IVIG within two weeks of symptom onset [30,31,35]. Nevertheless, we also offer IVIG for patients beyond two weeks from symptom onset, based on evidence of efficacy in the earlier time window.

Neither PLEX nor IVIG has been studied specifically in pregnant patients with GBS. Aggressive fluid loading prior to plasma exchange may help to avoid hypotension.

Immune globulin — IVIG is the preferred immunomodulatory treatment in most centers. Available evidence suggests that the efficacy of IVIG is similar to PLEX [31,41]. However, IVIG is easier to administer and the treatment can be implemented more quickly. Additionally, IVIG may be less likely than PLEX to be discontinued due to adverse effects [31,42].

●Administration – IVIG is given at 0.4 g/kg per day for five days to patients within four weeks of onset of GBS. We pretreat patients with 500 mL of normal saline and give acetaminophen 650 mg and diphenhydramine 25 mg, both 30 minutes before the infusion. The infusion is typically started slowly (0.3 to 0.5 mL/kg/hour depending on formulation) to monitor for adverse effects and increased every 15 to 30 minutes as tolerated up to 6 to 8 mL/kg/hour depending on formulation). The infusion is held or the rate reduced to address adverse effects. (See "Overview of intravenous immune globulin (IVIG) therapy".)

●Adverse effects – Adverse effects include hypotension, nausea, headache with or without aseptic meningitis, rash, acute kidney failure (mostly related to sucrose-containing products), and transfusion reactions. Rarely, patients may develop hyperviscosity leading to stroke or myocardial infarction. IgA deficiency can lead to anaphylaxis [43]; however, patients without IgA deficiency can also develop hypersensitivity reactions to IVIG, especially when exposed to different formulations.

●Efficacy – There are no trials comparing IVIG with placebo for the treatment of GBS; rather, the trials have compared IVIG with PLEX; IVIG and PLEX appear to have similar efficacy [44-46].

In a 2014 systematic review of clinical trials, functional disability at four weeks in 536 patients with GBS who received IVIG was similar to those who received PLEX (weighted mean difference -0.02, 95% CI -0.25 to 0.20) [31]. Patients assigned to IVIG were significantly less likely to discontinue treatment than those assigned to PLEX (relative risk 0.14, 95% CI 0.05-0.36) [31]. IVIG is regarded as effective as PLEX for the treatment of GBS according to a 2012 American Academy of Neurology guideline on IVIG for the treatment of neuromuscular disorders [41].

Plasma exchange — PLEX is an effective treatment for GBS. Because IVIG appears similarly effective and is easier to give, PLEX is less often used than IVIG. In addition, PLEX may be more likely than IVIG to be discontinued due to adverse effects [31,42].

●Administration – PLEX is usually given in four to six treatments over 8 to 10 days to patients within four weeks of onset of GBS. Two large-bore intravenous lines (or a single central line with a dual-lumen catheter) are needed to perform the plasma volume exchanges. The implementation of therapeutic PLEX, including techniques and regimens, is discussed in detail separately. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)

●Adverse effects – The main complications are hypotension, sepsis, transfusion reactions, and problems with intravenous access.

●Overall efficacy, timing, and number of exchanges – Large trials have established the effectiveness of PLEX to improve muscle strength, reduce the need for mechanical ventilation, and hasten recovery for patients with severe GBS [32,34,47,48]. A 2017 meta-analysis of six randomized controlled trials and 649 patients with GBS, treatment with PLEX was superior to supportive care [30]. Among 623 patients with GBS, those treated with PLEX were less likely than those receiving supportive care to require mechanical ventilation (14 versus 27 percent) and were likelier to achieve functional improvement by four weeks (57 versus 35 percent).

PLEX was most effective when started within seven days of symptom onset. However, in the North American study of 245 patients, those assigned to PLEX within 30 days after symptom onset had better short-term improvements and 6-month outcomes compared with those assigned placebo [32].

In one trial of 304 patients with moderately severe GBS, those who received four exchanges showed quicker improvement than those who received two, including a shorter time to ambulation (20 versus 24 days) and reduced time on mechanical ventilation (15 versus 37 days) [34]. However, six exchanges were not clearly superior to four. For patients with severe disease requiring mechanical ventilation who received six exchanges, there was a nonsignificant trend toward reduced time on mechanical ventilation compared with those who received four (median days 34 versus 43); however, the mean time to ambulation was not reduced after six exchanges (60 versus 56 days) and the rate of full strength at one year was not improved (53 versus 57 percent).

Other therapies not recommended — We recommend not giving glucocorticoids to patients with GBS. While the pathophysiology of GBS involves an inflammatory response against either the myelin or the axon of peripheral nerves, multiple trials have failed to show benefit with glucocorticoids [49].

The role of eculizumab in GBS remains unclear at this point and no recommendations for its routine use can be made. Activation of complement and formation of the membrane attack complex is the mechanism of peripheral nerve injury in both the demyelinating and axonal forms of GBS. Accordingly, the role of eculizumab in GBS has been investigated in Japan, and even though the study did not reach primary endpoint, outcomes at six months were improved with eculizumab [50,51].

APPROACH TO PATIENTS WHO RELAPSE OR WORSEN — Some patients diagnosed with GBS may continue to deteriorate after initial treatment with immunomodulatory therapy, either intravenous immune globulin (IVIG) or plasma exchange (PLEX). This may reflect the natural history of the disease or an error in diagnosis (algorithm 1) [52,53].

Approximately 40 percent of patients treated with IVIG or PLEX do not improve within the first four weeks after treatment [35,54]. Relapses with increased weakness occur in up to 10 percent of patients with GBS [55,56]. All patients who worsen should be reevaluated clinically to verify the accuracy of the diagnosis of GBS.

Retreatment may be offered for selected patients with GBS who have severe symptoms based on the lack of alternative options. However, there are no trial data to support the efficacy of this approach. (See 'The role for retreatment for some patients' below.)

Reevaluate the diagnosis — The diagnosis of GBS should be reevaluated for all patients whose neurologic and respiratory symptoms worsen during and after treatment with immunomodulatory therapy to assess for alternatives or to confirm the accuracy of fluctuating or severe GBS. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Diagnostic evaluation'.)

●Other acute polyneuropathies – The differential diagnosis of GBS includes other polyneuropathies and diseases of the spinal cord, neuromuscular junction, and muscle (table 3). Patients diagnosed with GBS whose symptoms fail to improve or worsen longer than four weeks after onset should undergo reevaluation including a full neurologic examination to assess for alternative diagnoses. As examples, patients with spinal cord pathology may present with acute flaccid paralysis and subsequently develop spasticity; those with myositis may report muscle tenderness or develop rhabdomyolysis. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Differential diagnosis'.)

●Treatment-related fluctuation or relapse – Some patients with GBS will have initial improvement after treatment with IVIG or PLEX followed by a secondary deterioration; these relapses are termed a "treatment-related fluctuation" (TRF) [57,58].

In one report of 147 patients with GBS who received immunotherapy, TRFs occurred in 10 percent of patients at a median of 21 days (range 10 to 60 days) after the start of treatment [57]. These relapses were typically not as severe as the initial progressive phase of GBS prior to treatment. Similar findings were noted in a prospective study of 170 patients with GBS, which reported that TRFs occurred in 9 percent of patients [58]. No patient with GBS had more than two TRFs.

●Chronic inflammatory demyelinating polyradiculoneuropathy – Approximately 2 to 5 percent of patients initially diagnosed with GBS will develop the chronic relapsing weakness of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) [21,58-60].

Distinguishing between GBS with TRFs and acute-onset CIDP can be difficult, but several clinical patterns may point to the diagnosis of CIDP rather than GBS [58]:

•Deterioration beyond eight weeks from onset of weakness

•Deterioration (relapse) occurs ≥3 times

•No loss of unaided ambulation

•Absence of cranial nerve involvement

CIDP is reviewed in detail separately. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Chronic inflammatory demyelinating polyneuropathy' and "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis".)

●Severe GBS – Some patients with severe GBS may fail to improve after immunotherapy due to severe axonal injury. Clinical features, severe initial deficits, and electrodiagnostic studies can help identify these patients. (See 'Risk factors for poor outcomes' below.)

The role for retreatment for some patients — Additional immunomodulatory treatment is occasionally considered for patients with severe symptoms who do not initially improve or whose improvement is transitory. Retreatment is somewhat controversial; it is typically offered due to the lack of alternative options as there is no trial evidence to support this approach. Other experts avoid retreatment for all patients with GBS owing to lack of demonstrated benefit and to avoid exposure to adverse effects [35,61].

We do not switch between immunotherapies due to lack of efficacy. In addition, switching to PLEX may reduce the effectiveness of initial IVIG therapy.

●When symptoms fail to improve – For patients with severe GBS treated initially with PLEX who show no improvement or further deterioration, retreating (no more than one time) with PLEX may be attempted at two weeks after initial treatment was begun, under close observation for side effects.

For those patients with severe GBS treated initially with IVIG, we suggest against retreating with IVIG because it exposes patients to adverse risks without additional benefit.

In a trial of 93 patients with acute GBS who were treated with an initial course of IVIG, patients with a predicted poor outcome were randomized to a second round of IVIG or placebo beginning within 9 days of the start of the first treatment [61]. At four-week follow up, those assigned to a second round of IVIG treatment had similar disability scores and more adverse effects (17 versus 7) compared with those who received placebo. A small observational study likewise found no improvement in outcomes for patients treated with a second course of IVIG started either two or four weeks after the initial course [62].

●When symptoms worsen after initial improvement – For patients with TRF within the first eight weeks after symptom onset, we suggest retreatment with the immunomodulatory therapy given initially, but its effectiveness is unclear [35].

RECOVERY AND LONG-TERM MANAGEMENT

Rehabilitation — Acute-phase rehabilitation should include an individualized program of gentle strengthening involving isometric, isotonic, isokinetic, and manual-resistive and progressive-resistive exercises [2]. Rehabilitation should emphasize proper limb positioning, posture, and orthotics as well as nutrition. A device to help with communication may be necessary for patients with bulbar weakness.

After the acute phase, disabled patients should be treated by a multidisciplinary rehabilitation team [63].

Fatigue — Fatigue is an underrecognized but common symptom in patients with GBS [64]. It can persist for years and lead to significant disability. Fatigue may be worse in patients with axonal forms of the disease [65]. Contributory factors such as deconditioning and depression need to be considered. A graded supervised exercise program can be beneficial [66].

Subsequent immunizations — For most patients with a history of GBS, we suggest giving routine vaccinations (figure 1 and figure 2), but the benefits of any vaccination should be balanced with the risks from the infection at an individual level. Data on vaccination in this setting are limited to observational studies and expert opinion [2,67,68]. However, the risk of GBS triggered by vaccine administration is very low (one to two excess cases of GBS per million people vaccinated) and is substantially less than the overall health risk posed by an illness from infection. In addition, vaccination may reduce the risk of GBS that may be triggered by infection. This issue is discussed separately. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Vaccinations'.)

For most patients with a history of GBS who have risk factors for severe influenza complications (table 4), the established benefits of influenza vaccination justify yearly vaccination. The utility of influenza vaccination in adults is discussed separately. (See "Seasonal influenza vaccination in adults".)

Because of the possible increased risk of GBS associated with the Janssen/Johnson & Johnson (Ad26.COV2.S) COVID-19 vaccine, for patients with a history of GBS, we suggest using other available COVID-19 vaccines. (See "COVID-19: Vaccines", section on 'Guillain-Barré syndrome'.)

The utilities of vaccination for other diseases (eg, pneumococcal pneumonia, hepatitis) are discussed in separate topic reviews. (See "Standard immunizations for nonpregnant adults".)

Circumstances when vaccinations may be delayed or withheld include the following:

●Delayed routine vaccination is suggested for patients who are within three months to one year after the onset of GBS.

●Future avoidance is suggested when GBS occurs within six weeks following any specific immunization (ie, vaccination-related GBS).

We do not give vaccinations to patients who are in the acute phase of GBS due to concerns that immunotherapies for GBS may reduce the immune response to vaccination. (See "Overview of intravenous immune globulin (IVIG) therapy", section on 'Vaccination of patients receiving IVIG'.)

PROGNOSIS — Functional recovery after GBS occurs over several weeks and the extent of improvement is variable, depending on individual risk factors.

Long-term outcome — The long-term prognosis is favorable for most patients with GBS. Approximately 80 percent of patients are able to walk independently and more than half recover completely by one year [69]. However, severe motor impairments persist in more than 10 percent. Approximately 5 to 10 percent of patients with GBS have a prolonged course with several months of ventilator dependency and very delayed and incomplete recovery [70].

Mortality risk appears highest during recovery. In one study of 527 patients with GBS, the median time from symptom onset to death was 76 days, most frequently from respiratory or cardiovascular complications [71]. Approximately 3 to 7 percent of patients with GBS die despite intensive care [69,71,72]. Among patients who become ventilator dependent, mortality is approximately 20 percent. Causes of death include acute respiratory distress syndrome, sepsis, pulmonary emboli, and unexplained cardiac arrest [73].

Risk factors for poor outcomes — Factors associated with a poor prognosis for recovery from GBS include [1,69,71,74,75]:

●Age >60 years

●Rapid onset of weakness (less than seven days from symptom onset to hospital admission)

●Severe muscle weakness on admission

●Need for ventilatory support

●Preceding diarrheal illness

●Severe electrodiagnostic testing abnormalities

Electrodiagnostic studies can aid with prognosis by identifying electrodiagnostic features associated with a poor prognosis. The prognosis for improvement is typically good when the disease is demyelinating since remyelination is an efficient repair mechanism [76,77]. The prognosis for recovery is worse for patients with secondary axonal degeneration or when the primary attack is against the axon as in the acute motor axonal neuropathy (AMAN) variant.

Axonal degeneration and poor prognosis (ie, slower recovery and/or severe residual disability) are suggested by markedly reduced distal CMAP amplitude (<20 percent of normal) and profuse fibrillation potentials on needle examination, starting at two to four weeks after disease onset [78,79]. By contrast, demyelination and a good prognosis are associated with a pattern characterized by CMAP amplitude above 20 percent of normal, predominantly demyelinating findings such as conduction block, and temporal dispersion.

Clinical prognostic scores — The Erasmus GBS outcome score (EGOS) and modified Erasmus global outcome score (mEGOS) systems can be used to estimate the risk of being unable to walk at six months [1,80].

●The EGOS is assessed two weeks after admission and scored 0 to 7, incorporating patient age, the presence or absence of diarrhea, and the GBS disability score [80].

●The mEGOS may be calculated one week after admission and is scored 0 to 12. It also incorporates patient age, the presence or absence of preceding diarrhea, and the MRC sum score (table 1) [1].

In the initial EGOS derivation and validation data sets including 762 patients, the rate of being unable to walk at 6 months was 27 percent for patients with a score of 5 compared with 52 percent for patients with a score of 7, the highest score [80]. By contrast, for a patient evaluated at one week with the mEGOS highest score of 12, the estimated risk of being unable to walk at six months was 66 percent [1]. The limitation of these scoring systems is that the data are derived from a White Dutch population and may not be applicable to other populations [76-79].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Guillain-Barré syndrome".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Guillain-Barré syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Triage – Patients with Guillain-Barré syndrome (GBS) should be admitted to an inpatient setting for serial hemodynamic and neurologic monitoring and to guide therapy (algorithm 1). (See 'Triage' above.)

•Baseline neurologic, respiratory, and hemodynamic evaluations should be performed at admission.

•We admit (or transfer) patients to an intensive care unit (ICU) setting who present with weakness that is severe or rapidly progressive and are at high risk for respiratory failure, those with signs of imminent respiratory failure, and those with autonomic dysfunction. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) scale is used to predict the risk of respiratory failure within the first week of admission.

●Supportive care for all patients – All patients with GBS should be monitored for deterioration of neurologic, respiratory, cardiovascular, and autonomic status with supportive care to address symptoms or their progression (algorithm 1). (See 'Supportive management and monitoring' above.)

●Immunomodulatory therapy – Immunotherapy with either intravenous immune globulin (IVIG) or plasma exchange (PLEX) is effective for disease-modifying treatment in GBS. The choice between PLEX and IVIG is dependent on local availability and on patient preference, risk factors, and contraindications. (See 'Immunomodulatory therapy' above.)

•For nonambulatory adult patients with GBS who are within four weeks of symptom onset, we recommend treatment with PLEX or IVIG (Grade 1A).

•For ambulatory adult patients with GBS who are not yet recovering within four weeks of neuropathic symptom onset, we suggest treatment with PLEX or IVIG (Grade 2B).

•For adult patients with GBS, we recommend not treating with glucocorticoids due to lack of benefit and possible delay in recovery (Grade 1B). (See 'Other therapies not recommended' above.)

●Approach to patients who relapse or worsen – The diagnosis of GBS should be reevaluated for all patients whose symptoms worsen or fluctuate with initial immunomodulatory therapy. Some experts offer retreatment for selected patients with GBS who have severe symptoms based on the lack of alternative options. However, there are no trial data to support the efficacy of this approach (algorithm 1). (See 'Approach to patients who relapse or worsen' above.)

•We do not switch between IVIG or PLEX due to lack of efficacy.

•For patients with severe GBS who show no improvement or further deterioration after initial treatment with PLEX, we suggest retreating (no more than one time) with PLEX at two weeks, under close observation for side effects (Grade 2C).

For patients with severe GBS treated initially with IVIG, we suggest against retreating with IVIG because it exposes patients to adverse risks without additional benefit (Grade 2C).

•For patients with treatment-related fluctuation after initial immunomodulatory treatment who are within the first eight weeks after symptom onset, we suggest retreatment with the immunomodulatory therapy given initially, under close observation for side effects (Grade 2C).

●Subsequent immunizations – For most patients, a history of GBS does not pose a contraindication to routine vaccination; patients should proceed with vaccinations that are recommended for their age group and comorbidities (figure 1 and figure 2). We do delay vaccine administration until they have recovered from GBS. (See 'Subsequent immunizations' above.)

●Prognosis – Approximately 80 percent of patients are able to walk independently and more than half recover completely by one year. However, severe motor impairments persist in more than 10 percent. (See 'Long-term outcome' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Francine J Vriesendorp, MD, who contributed to earlier versions of this topic review.