Guillain-Barré syndrome in children: Treatment and prognosis

INTRODUCTION — The acute immune-mediated polyneuropathies are classified under the eponym Guillain-Barré syndrome (GBS) after some of the authors of early descriptions of the disease. GBS is one of the most common causes of acute, acquired weakness and is often provoked by a preceding infection. GBS may be complicated in some cases by respiratory failure and autonomic dysfunction.

The management and prognosis of GBS in children will be reviewed here.

Other aspects of GBS in children are discussed separately. (See "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis".)

GBS in adults is presented elsewhere. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis" and "Guillain-Barré syndrome in adults: Treatment and prognosis".)

MONITORING AND SUPPORTIVE CARE — During the initial phase of GBS, all patients require close monitoring of motor, autonomic (ie, blood pressure, heart rate, and sphincter function), and respiratory function. Serial pulmonary function testing should be performed routinely. In most cases, pulmonary function monitoring (ie, vital capacity and maximum inspiratory pressure) should be performed every four hours at the bedside. All children, particularly those who are too young to cooperate with pulmonary testing, should be closely monitored and observed for fatigue and other clinical signs of impending respiratory muscle failure, as discussed below.

Patients should be electively intubated if clinical evaluation or pulmonary function tests suggest impending respiratory failure. Vigilance is essential since respiratory deterioration can occur rapidly. (See 'Ventilatory status' below.)

Mortality is often due to complications such as nosocomial infection, acute respiratory arrest, deep venous thrombosis with pulmonary embolism, and pneumothorax. Outcomes can be optimized with meticulous care in the intensive care unit to identify patients progressing to respiratory failure early and to prevent hospital-acquired complications.

Indication for ICU level of care — Children with any of the following problems should be admitted urgently to a pediatric intensive care unit (ICU) [1,2]:

●Flaccid quadriparesis

●Rapidly progressive weakness

●Reduced vital capacity (≤20 mL/kg)

●Bulbar palsy

●Significant autonomic instability

Less severely affected patients can be managed in intermediate care units if available, and mildly affected patients whose trajectory is stable can be managed on the general ward, preferably with cardiac telemetry, along with monitoring of blood pressure and vital capacity every four hours. Hospitalization is continued until the child's condition has clearly stabilized.

Ventilatory status — Up to 20 percent of children with GBS require mechanical ventilation for respiratory failure [3-5]. The need for tracheal intubation should be anticipated so that it can be performed as an elective procedure [6].

Risk factors for respiratory failure include [5,7,8]:

●Shorter time from onset of neurologic symptoms to admission

●Cranial nerve involvement

●Autonomic dysfunction

●Higher GBS disability score at admission

●Higher CSF protein level

●Axonal forms of GBS

●Older age

The Erasmus GBS Respiratory Insufficiency Scale for children (EGRIS-Kids) is a prognostic model designed to predict risk of respiratory failure in children with GBS [5]. The scale assigns points for age (0 for ≤5 years, 1 for 6 to 10 years, 2 for >10 years), GBS disability scale score at admission (1 to 4 for nonintubated scores in scale), and cranial nerve involvement (0 for absence, 3 for presence). The scale is scored from 1 to 9; results correlate with the risk of respiratory failure ranging from 4 to 50 percent.

Children with a vital capacity approximately one-half the normal value for age or ≤20 mL/kg of body weight generally progress to require ventilatory support. In one study of patients with GBS that included some children, serial measurements of pulmonary function were most helpful for detecting the risk of developing respiratory failure [9].

The following parameters warn of impending respiratory arrest and are an indication for urgent intubation [9]:

●Vital capacity ≤20 mL/kg

●Maximum inspiratory pressure less negative than -30 centimeters of water (cmH₂O; ie, between -30 and 0 cmH₂O)

●Maximum expiratory pressure ≤40 cmH₂O

●Tidal volume <5 mL/kg

Pulmonary function testing is difficult in children who cannot cooperate, typically those younger than six years of age. These patients should be closely monitored and observed for fatigue and other clinical signs of impending respiratory muscle failure. These signs include the following:

●A sustained increase in partial pressure of carbon dioxide (pCO₂) to ≥50 mmHg (normally 35 to 40 mmHg)

●An increasing respiratory rate

●Increasing oxygen requirement and increasing alveolar to arterial oxygen difference (normally 5 to 10 mmHg)

●An increased use of accessory muscles (eg, sternocleidomastoid use, flaring of the alae nasi, intercostal retractions) and decreased or paradoxical diaphragm movements; these reflect decreased chest wall movement and low lung volumes

●Sweating about the head and neck, wide pulse pressure, and bounding pulses; these portend respiratory failure with carbon dioxide (CO₂) retention

Children have less metabolic and muscle reserve than adults. They can deteriorate quite rapidly and suddenly become apneic or develop alveolar hypoventilation. Generally, it is wise to have a pediatric critical care specialist involved early in the clinical course.

Sedation and neuromuscular blockade should be avoided where possible in ventilated patients because they obscure the course of the illness. Scrupulous airway care and chest physiotherapy reduce the risk of pneumonia. Tracheostomy may be needed if prolonged ventilation is required.

Autonomic status — Autonomic dysfunction is a well-recognized feature of GBS and is a significant source of mortality [6,10]. Consequently, close monitoring of blood pressure, fluid status, and cardiac rhythm are essential to the management of these patients. Care must also be taken when vasoactive or sedative drugs are used, because GBS-related dysautonomia may exaggerate the hypotensive responses to these drugs.

Other supportive measures — Nutritional needs should be addressed early in the disease course. Orogastric tube feeding, gastrostomy, or parenteral nutrition is often necessary.

The patient's position should be changed frequently for comfort and to avoid skin breakdown. Intermittent-pressure leg boots are used in the intensive care setting to prevent deep vein thrombosis.

Pain is prominent and distressing for many children with GBS and their families. Early recognition and treatment of neuropathic pain is important to facilitate comfort and participation in physical therapy [11]. (See "Pain in children: Approach to pain assessment and overview of management principles".)

Physical therapy, occupational therapy, and social services should be involved early. Providing the patient with a method of communication is important if normal speech is not possible. Pencil and paper or a communication board can be given to those old enough to write.

IMMUNOTHERAPIES — The main modalities of therapy for GBS are intravenous immune globulin (IVIG) and plasma exchange (also called plasmapheresis). While acknowledging the limitations of data for children, we suggest treatment with IVIG or plasma exchange for children with severe GBS, in general agreement with guidelines from the American Academy of Neurology (AAN) and other consensus statements [2,11-13].

Glucocorticoids are not beneficial for GBS and have no role in its treatment [14-16].

Indications for treatment — IVIG and plasma exchange for children with GBS should be reserved for those with any of the following indications [2]:

●Progressing weakness

●Worsening respiratory status or need for mechanical ventilation

●Significant bulbar weakness

●Inability to walk unaided

IVIG and plasma exchange are not recommended for children with mild symptoms who are unlikely to benefit from these therapies, including those who are ambulatory, who have mild, nonprogressive disease, or for children whose mild symptoms have stabilized. Children who have rapid progression followed by stabilization of symptoms within the first or second week of GBS onset may still be considered candidates for treatment by some child neurologists.

Time to treatment onset may be important in children although data are lacking. In general, IVIG is recommended for patients who are unable to walk unaided if treatment is started within two or possibly four weeks of onset. Similarly, plasma exchange is recommended for patients who are unable to walk unaided if treatment is started within four weeks of symptom onset [12,17,18].

Selection of agent — IVIG is preferred to plasma exchange in children because of the relative safety and ease of administration, although there are no high-quality data to suggest that one is superior to the other. In a randomized trial from Egypt that enrolled 41 children with very severe GBS necessitating ventilatory support, there was no significant difference between treatment with plasma exchange versus IVIG for length of stay in the pediatric intensive care unit or for ability to walk unaided at four weeks after discharge [19]. However, the duration of mechanical ventilation was significantly shorter for the group treated with plasma exchange (median 11 days, versus 13 days for IVIG). This finding requires confirmation in larger, more rigorous trials. In adults, IVIG and plasma exchange are equally effective [17]. (See "Guillain-Barré syndrome in adults: Treatment and prognosis", section on 'Selection of agent'.)

Intravenous immune globulin — Reports of the use of IVIG in children with GBS are limited, and no large randomized controlled trials exist. Nevertheless, data from the available small open-label randomized trials in children suggest that IVIG shortens the time to recovery compared with supportive care alone [17,20,21]. Similarly, most observational studies show that IVIG hastens recovery in children [22-26]. While these trials and studies in children have not proven that IVIG leads to improvement in overall prognosis, their results are consistent with the larger randomized trials showing a beneficial effect of IVIG treatment for GBS in adults. (See "Guillain-Barré syndrome in adults: Treatment and prognosis".)

The mechanism of improvement with IVIG is uncertain, but it is thought to involve suppression of inflammatory and immune-mediated processes. This is discussed separately. (See "Overview of intravenous immune globulin (IVIG) therapy", section on 'Suppression of inflammatory/autoimmune processes'.)

Methodologic differences between reports make it difficult to generalize about when children with GBS begin to improve after IVIG treatment. Nevertheless, muscle strength generally begins to improve in most children within 14 days after initiation of IVIG therapy and most are walking within three months [24-26]. Early transient relapse (or "treatment-related fluctuations") after IVIG treatment has been reported [21,27-29].

●Dosing – The total dose of IVIG for the treatment of GBS in children is 2 g/kg, given as 1 g/kg for two days or 400 mg/kg for five days. This dose is empiric and is based upon treatment of patients with immune deficiency disorders. The dosage schedule is also empiric as little is known of the pharmacokinetics of serum immunoglobulin G (IgG) [30]. Many centers give a total of 2 g/kg of IVIG over two days, however one small trial suggested a slightly greater risk of treatment-related fluctuations with this regimen as opposed to a five-day course [21].

Typically, patients are given only a single course of IVIG treatment. There is very little evidence to support an additional course of IVIG in severe cases of GBS or in patients showing no recovery within two weeks of presentation. A randomized, placebo-controlled trial in adults with GBS who had a predicted poor prognosis not only failed to show benefit from a second course of IVIG, but also showed increased rates of serious adverse events with repeat treatment [31].

Patients with a treatment-related fluctuation (defined as disease progression occurring within two months following an initial treatment-induced clinical improvement or stabilization) however, may respond to a second course of IVIG, although evidence for this is limited [2,18,32].

●Adverse effects – Complications and side effects of IVIG treatment are those related to transfusion reactions and are discussed elsewhere. (See "Immunologic transfusion reactions".)

Plasma exchange — Large multicenter trials have established the effectiveness of plasma exchange in adult patients with severe GBS. The mechanism is thought to be removal of antibodies directed against nerves from the circulation. Increased muscle strength, earlier neurologic improvement, and a less frequent need for mechanical ventilation have been demonstrated, as discussed separately.

In an meta-analysis of six trials and 649 patients with GBS that included a small number of children who were all ≥10 years of age, treatment with plasma exchange was superior to supportive care [18]. Plasma exchange was most effective when started within seven days of symptom onset but may still be beneficial if started within four weeks of initial symptoms. Compared with supportive care, patients treated with plasma exchange had a slightly higher risk of relapse in the first year after treatment but nevertheless were more likely at one year to have full recovery of muscle strength.

In general, results of plasma exchange in pediatric patients appear to be similar to those in adults, with a shortened disease course and reduced incidence of respiratory failure. The main benefit seems to be a decrease in the interval from maximum weakness to recovery of independent walking [33].

As a result of the cost, risk, and discomfort to the patient, plasma exchange generally is not used in very young children, for ambulatory patients with mild disease, or for patients whose symptoms have stabilized.

●Procedure – Plasma exchange requires special equipment and trained personnel and can be performed only at centers with expertise in the treatment of children. Because of technical considerations, this procedure is more challenging in children younger than two years of age. The procedure usually consists of four to six double-volume exchanges performed on alternate days over one week. Immunoglobulin levels may be decreased by 30 to 40 percent after plasma exchange.

●Complications – The frequency and types of complications from therapeutic apheresis depend on the overall condition of the patient, the number of plasma exchanges, the replacement fluid, and the venous access device. For all therapeutic apheresis, patients may be at risk for citrate-induced hypocalcemia, metabolic alkalosis, or complications related to the vascular catheter. Potential early symptoms of hypocalcemia include perioral and distal extremity paresthesias or numbness; severe reactions can include tetany, prolongation of the QT interval, arrhythmias, or hypotension. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Complications".)

Younger children most often require placement of a central venous catheter. Potential complications of central venous catheters include infection, pain, nerve damage, thrombosis, perforation, dissecting hematomas, air embolism, or arteriovenous fistulas. Many of these complications can also occur if peripheral veins are used.

PROGNOSIS — In general, the prognosis of GBS in children is better than in adults [7,34-37]. In various reports, the following observations were noted:

●Mortality is generally less than 2 to 3 percent in most pediatric GBS cohorts [5,38-40]. However mortality rates are higher in resource-limited settings [41].

●Approximately 90 percent of children were ambulatory within six months after onset, and nearly all (96 percent) walk within one year [39].

●An excellent long-term recovery (eg, symptom-free or no disability despite residual symptoms) was observed in 85 to 92 percent of children [15,42,43].

●In a study of 52 children with a median follow-up of 11 years, sequelae of GBS were reported by 65 percent of patients; the most common residual complaints were paresthesia, unsteady gait in the dark, painful hands or feet, and severe fatigue. Long-term neurologic deficits included sensory loss, limb weakness, and areflexia in 14, 8, and 5 percent, respectively [43].

●Treatment-related fluctuations occur in up to 7 percent of cases of childhood GBS and are generally responsive to immunomodulatory treatment [34]. Approximately 2 percent of children go on to have recurrent weakness and are ultimately diagnosed with chronic inflammatory demyelinating polyneuropathy [34]. (See "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis".)

●Recurrence of GBS was reported in 2 to 5 percent [34,43], which can occur months to years after the initial episode.

Although most children with GBS experience excellent recovery, outcomes may be less favorable in the following groups [7,39,40,44-48]:

●Very young age (<2 years)

●Severe weakness at presentation

●Rapid progression of weakness

●Cranial nerve involvement

●Require ventilator support

●Have inexcitable motor nerves on nerve conduction studies

The long-term outcome of GBS does not appear to differ substantially among the GBS subtypes [43,47,49,50] (see "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis", section on 'Variant forms of Guillain-Barré syndrome'). In an observational study of Japanese children with GBS, outcomes were generally favorable in both acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) subtypes, although delayed recovery was more frequent with AMAN [49]. All 11 children with AIDP and 12 of 15 (80 percent) with AMAN regained the ability to walk independently at six months; 14 of 15 children (93 percent) with AMAN walked independently at two years. Differences in clinical recovery between children with AIDP and AMAN were not statistically significant.

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".)

SUMMARY AND RECOMMENDATIONS

●Supportive care – All patients with Guillain-Barré syndrome (GBS) require close monitoring of motor, autonomic (ie, blood pressure, heart rate, and sphincter function), and respiratory function during the acute phase of the illness. (See 'Monitoring and supportive care' above.)

•Indication for ICU level of care – Children with GBS who have flaccid quadriparesis, rapidly progressive weakness, reduced vital capacity (≤20 mL/kg), bulbar palsy, or autonomic instability should be admitted emergently to a pediatric intensive care unit. (See 'Indication for ICU level of care' above.)

•Ventilatory status – Vital capacity and maximum inspiratory pressure should be assessed every four hours at the bedside. All children, particularly those too young to cooperate with pulmonary testing, should be closely monitored and observed for fatigue and other clinical signs of impending respiratory muscle failure. (See 'Ventilatory status' above.)

Clinical signs of impending respiratory muscle failure include a sustained increase of partial pressure of carbon dioxide (_pCO₂) to ≥50 mmHg, increasing respiratory rate, an increased use of accessory muscles and decreased or paradoxical diaphragm movements, sweating about the head and neck, wide pulse pressure, and bounding pulses.

Parameters that warn of impending respiratory arrest and are an indication for elective intubation include:

-Vital capacity ≤20 mL/kg

-Maximum inspiratory pressure less negative than -30 centimeters of water (cmH₂O; ie, between -30 and 0 cmH₂O)

-Maximum expiratory pressure ≤40 cmH₂O

-Tidal volume <5 mL/kg

•Autonomic dysfunction – Autonomic dysfunction is a well-recognized feature of GBS and is a significant source of mortality. Therefore, management requires close monitoring of blood pressure, fluid status, and cardiac rhythm. (See 'Autonomic status' above.)

●Immunotherapies – We suggest treatment with intravenous immune globulin (IVIG) or plasma exchange for children with severe GBS (Grade 1B), as defined by the presence of one or more of the following characteristics (see 'Immunotherapies' above):

•Progressing weakness

•Worsening respiratory status or need for mechanical ventilation

•Significant bulbar weakness

•Inability to walk unaided

We prefer IVIG to plasma exchange for the treatment of children because of its relative safety and ease of administration, although it has not been shown to have better results. Neither treatment is recommended for ambulatory children with GBS who have mild disease or for children whose symptoms have stabilized. However, children who have rapid progression followed by stabilization of symptoms within the first or second week of GBS onset may still be considered candidates for treatment. (See 'Immunotherapies' above.)

●Prognosis – Data regarding the prognosis of GBS in children suggest a mortality rate of up to 2 to 3 percent and an excellent long-term recovery (eg, symptom-free or no disability despite residual symptoms) in 90 percent or more of children. (See 'Prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Robert P Cruse, DO, who contributed to an earlier version of this topic review.