AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Guillain-Barré syndrome (GBS) may be described as a collection of clinical syndromes manifested by an acute inflammatory polyradiculoneuropathy with resultant weakness and diminished reflexes. With poliomyelitis under control in developed countries, GBS is now the most important cause of acute flaccid paralysis. GBS remains a diagnosis made primarily by clinical history and findings. While the classic description is that GBS is as a demyelinating neuropathy with ascending weakness, many clinical variants have been well documented in the medical literature. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is the most widely recognized form in Western countries, but the recently described variants of acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) also are well recognized. Many believe that strictly defined subgroups of GBS are not distinguished easily but that the subgroups exist, based on a clinical spectrum of symptoms and findings.

Pathophysiology

GBS is a postinfectious immune-mediated disease. Both cellular and humoral immune mechanisms probably play a role in its development. Most patients report an infectious illness in the weeks prior to the onset of GBS. Many of the identified infectious agents are thought to induce antibody production against specific gangliosides and glycolipids, such as GM1 and GD1b, distributed throughout the myelin in the peripheral nervous system.

The pathophysiologic mechanism of an antecedent illness and GBS can be typified by Campylobacter jejuni infections. The virulence of C jejuni is thought to be based on the presence of specific antigens in its capsule that are shared with nerves. Immune responses directed against the capsular components produce antibodies that cross-react with myelin to cause demyelination. Ganglioside GM1 appears to cross-react with C jejuni lipopolysaccharide antigens, resulting in the immunologic damage to the peripheral nervous system. This process has been termed molecular mimicry.

Pathological findings in GBS include lymphocytic infiltration of spinal roots and peripheral nerves, followed by macrophage-mediated multifocal stripping of myelin. This phenomenon results in defects in the propagation of electrical nerve impulses with eventual conduction block and flaccid paralysis. In some patients with severe disease, a secondary consequence of the severe inflammation is axonal disruption and loss. A subgroup of patients may have a primary immune attack directly against nerve axons, resulting in a similar clinical presentation.

Variants

Several variants of GBS are recognized. These disorders share similar patterns of evolution, recovery, symptom overlap, and probable immune-mediated pathogenesis.

• The Miller-Fisher syndrome is a common variant of GBS and is observed in about 5% of all GBS cases. The syndrome consists of ataxia, ophthalmoplegia, and areflexia. Ataxia primarily is noted during gait and in the trunk with lesser involvement of the limbs. Motor strength characteristically is spared. The usual course is one of gradual and complete recovery over weeks to months. A close association exists between antiganglioside antibodies and the Fisher variant. Anti-GQ1b antibodies, triggered by certain C jejuni strains, have a relatively high specificity and sensitivity for the disease. Dense concentrations of GQ1b ganglioside are found in the oculomotor, trochlear, and abducens nerves, which may explain the relationship between anti-GQ1b antibodies and ophthalmoplegia.
• The AMAN variant is associated closely with enteric C jejuni infections and high titers of antibodies to gangliosides (ie, GM1, GD1a, GD1b). Patients with AMAN have pure motor symptoms and appear clinically very similar to patients with the demyelinating form of GBS with ascending symmetric paralysis. AMAN is distinguished by electrodiagnostic study results that are consistent with a pure motor axonopathy. Biopsies show wallerianlike degeneration without significant lymphocytic inflammation. Many cases have been reported in rural areas of China, especially in children and young adults during the summer months. Pure axonal cases may occur more frequently in other parts of the world outside Europe and North America. AMAN cases also may be different from cases of axonal GBS described in the West. Prognosis is often quite favorable. Although recovery for many is rapid, severely disabled patients with AMAN may still show improvement over a period of years.
• The axonal form of GBS, also referred to as acute motor-sensory axonal neuropathy (AMSAN), often presents with rapid and severe paralysis with delayed and poorer recovery compared to the electrophysiologically similar AMAN cases. Like AMAN, axonal GBS also is associated with preceding C jejuni diarrhea. Pathologic findings show severe axonal degeneration of motor and sensory nerve fibers with little demyelination.
• A pure sensory variant of GBS has been described in the medical literature, typified by rapid onset of sensory loss and areflexia in a symmetric and widespread pattern. Lumbar puncture studies show albuminocytologic dissociation in the cerebral spinal fluid (CSF) and electromyography (EMG) results show characteristic signs of a demyelinating process in the peripheral nerves. Prognosis is generally good, but immunotherapies, such as plasma exchange and intravenous immunoglobulins (IVIG), can be tried in patients with severe disease or slow recovery.
• Acute pandysautonomia without significant motor or sensory involvement is a rare presentation of GBS. Dysfunction of the sympathetic and parasympathetic systems results in severe postural hypotension, bowel and bladder retention, anhidrosis, decreased salivation and lacrimation, and pupillary abnormalities.
• The pharyngeal-cervical-brachial variant is distinguished by isolated facial, oropharyngeal, cervical, and upper limb weakness without lower limb involvement. Other unusual clinical variants with restricted patterns of weakness are observed only in rare cases.

Frequency

United States

In a recent epidemiological survey in the United States, the average annual incidence was 3.0 cases per 100,000 population. In comparing age groups, the annual mean rate of hospitalizations related to GBS increased with age with a rate of 1.5 cases per 100,000 population in persons aged less than 15 years to a peak of 8.6 cases per 100,000 in persons aged 70-79 years.

International

GBS is widespread and has been reported throughout the world. Most studies show similar figures for annual incidence as in the United States without geographical clustering.

Mortality/Morbidity

In epidemiologic surveys, the overall death rates range from 2-12% of patients. GBS-associated mortality rates increase markedly with age. In the United States, the case-fatality ratio ranges from 0.7% among persons younger than 15 years to 8.6% among persons older than 65 years. In surveying patients aged 60 years or older, the risk of death increases 6-fold compared with persons aged 40-59 years and increased 157-fold compared with persons younger than 15 years. Although the death rate increases with age in both males and females, males have a death rate 1.3 times greater than females after age 40 years.

GBS-related deaths usually occur in ventilator-dependent patients due to complications such as pneumonia, sepsis, adult respiratory distress syndrome, or, less frequently, autonomic dysfunction. Underlying pulmonary disease and the need for mechanical ventilation increase the risk of death, especially in elderly patients. Length of hospital stays also increases with advancing age, due to disease severity and associated medical complications.

Race

GBS has been reported throughout the international community. In North America, Western Europe, and Australia, most patients with GBS meet electrophysiologic criteria for demyelinating polyneuropathy. In northern China, up to 65% of patients with GBS have axonal pathology.

Sex

A slight male preponderance is seen in most studies, especially in older patients.

Age

GBS cases have been reported in all age ranges from infancy through old age. In the United States, the age distribution appears to be bimodal, with the largest peak in the elderly population, followed by young adults. Infants appear to be at the lowest risk for developing GBS.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Antecedent illness
• • Up to two thirds of patients with GBS report an antecedent illness or event 1-3 weeks prior to the onset of weakness. Upper respiratory and gastrointestinal illnesses are the most commonly reported conditions. Symptoms generally have resolved by the time of medical presentation for the neurologic condition.
  • C jejuni is the major organism identified in most studies and is responsible for both AIDP and AMAN cases. In one major study, previous diarrheal illness had occurred in 60% of patients with axonal GBS by neurophysiologic testing.
  • Vaccinations, surgical procedures, and trauma have been reported as triggers for GBS. Much of this information is anecdotal, although vaccination with the 1976 swine flu vaccine was shown to carry a small, but definable, increased risk of contracting GBS. Other studies of vaccinations have not shown a significant relationship with GBS.
• Weakness
• • The classic clinical picture of weakness is ascending and symmetrical in nature. The lower limbs usually are involved before the upper limbs. Proximal muscles may be involved earlier than the more distal ones. Trunk, bulbar, and respiratory muscles can be affected as well.
  • Weakness develops acutely and progresses over days to weeks. Severity may range from mild weakness to complete tetraplegia with ventilatory failure. Peak deficits are reached by 4 weeks after initial development of symptoms. Progression of symptoms beyond that point brings the diagnosis under question. Recovery usually begins 2-4 weeks after progression ceases.
• Sensory changes
• • Most patients complain of paresthesias, numbness, or similar sensory changes. Sensory symptoms often precede the weakness. Sensory symptoms frequently are ascending in nature and are more pronounced in a distal distribution.
  • Sensory symptoms are usually mild. Objective findings of sensory loss tend to be minimal and variable in most cases.
  • On nerve conduction studies (NCS), 58-76% of patients exhibit sensory abnormalities.
• Cranial nerve involvement
• • Cranial nerve involvement is observed in 45-75% of patients with GBS. Common complaints may include the following:
    • Facial droop
    • Diplopias
    • Dysarthria
    • Dysphagia
  • Facial and oropharyngeal weakness usually appears after the trunk and limbs are affected.
• Pain
• • In a prospective, longitudinal study of pain in patients with GBS, 89% of patients reported pain attributable to GBS at some time during their illness. On initial presentation, almost 50% of patients described the pain as severe and distressing.
  • The mechanism of pain is uncertain and may be a product of several factors. Pain can be due to direct nerve injury or the paralysis and prolonged immobilization.
  • Most patients complain of back and leg pain, often described as aching or throbbing in nature. The mechanism of pain is thought to be inflamed nerve roots. Dysesthetic symptoms are observed in approximately 50% of patients during the course of their illness. Dysesthesias frequently are described as burning, tingling, or shocklike sensations and are often more prevalent in the lower extremities than in the upper extremities. Dysesthesias may persist indefinitely in 5-10% of patients. Other pain syndromes in GBS can include myalgic complaints with cramping and local muscle tenderness, visceral pain, and pain associated with conditions of immobility (eg, pressure nerve palsies, decubitus ulcers).
  • Intensity of pain on admission correlates poorly with neurologic disability on admission and end outcome.
• Autonomic changes
• • Autonomic nervous system involvement with dysfunction in the sympathetic and parasympathetic systems can be observed in patients with GBS.
  • Autonomic changes can include the following:
    • Tachycardia
    • Bradycardia
    • Facial flushing
    • Paroxysmal hypertension
    • Orthostatic hypotension
    • Anhidrosis and/or diaphoresis
  • Urinary retention and paralytic ileus also can be observed. Bowel and bladder dysfunction rarely presents as an early symptom or persists for a significant period of time.
  • Dysautonomia is more frequent in patients with severe weakness and respiratory failure.
  • Autonomic changes rarely persist in the patient with GBS.
• Respiratory involvement
• • Upon presentation, 40% of patients have respiratory or oropharyngeal weakness.
  • Typical complaints may include the following:
    • Dyspnea on exertion
    • Shortness of breath
    • Difficulty swallowing
    • Slurred speech
    • Ventilatory failure with required respiratory support is observed in up to one third of patients at some time during the course of their disease.

Physical

• Vital signs
• • Cardiac arrhythmias, including tachycardias and bradycardias, can be observed due to autonomic nervous system involvement.
• Tachypnea may be a sign of ongoing dyspnea and progressive respiratory failure.
• Blood pressure lability is also a common feature with alterations between hypertension and hypotension.
• Cranial nerves
• • Facial weakness (cranial nerve VII) is observed most frequently, followed by symptoms associated with cranial nerves VI, III, XII, V, IX, and X. Involvement of facial, oropharyngeal, and ocular muscles results in facial droop, dysphagia, dysarthria, and findings associated with disorders of the eye.
  • Ophthalmoparesis may be observed in up to 25% of patients with GBS. The most common limitation of eye movement is from a symmetric palsy associated with cranial nerve VI. Ptosis from cranial nerve III (oculomotor) palsy often is associated with limited eye movements. Pupillary abnormalities also are relatively common, especially accompanying ophthalmoparesis.
• Motor examination
• • Lower extremity weakness usually begins first and ascends symmetrically and progressively over the first several days.
  • Upper extremity, trunk, facial, and oropharyngeal weakness is observed to a variable extent.
  • Marked asymmetric weakness calls the diagnosis of GBS into question.
• Sensory examination
• • Despite frequent complaints of paresthesias, objective sensory changes are minimal.
  • A well-demarcated sensory level should not be observed in patients with GBS, and such a finding calls the diagnosis of GBS into question.
• Reflex changes
• • Reflexes are absent or hyporeflexic early in the disease course and represent a major clinical finding on examination of the patient with GBS.
  • Pathologic reflexes, such as Babinski, are absent.
  • Hypotonia can be observed with significant weakness.

Causes

GBS is considered to be a postinfectious immune-mediated disease targeting peripheral nerves. Up to two thirds of patients report an antecedent illness prior to the onset of neurologic symptoms. Respiratory infections are reported most frequently, followed by gastrointestinal infections.

Campylobacter jejuni is the most common pathogen isolated in several studies. Serology studies in the Dutch Guillain-Barré trial identified 32% of patients as having had a recent C jejuni infection, while studies in northern China documented infection rates as high as 60%. Both gastrointestinal and upper respiratory tract symptoms can be observed with C jejuni infections. C jejuni infections also can have a subclinical course, resulting in patients with no reported infectious symptoms prior to development of GBS. Patients with GBS following an antecedent C jejuni infection often have a more severe course with rapid progression and prolonged incomplete recovery. A strong clinical association has been noted between C jejuni infections, pure motor forms of GBS, and axonal forms of GBS.

The virulence of C jejuni is thought to be based on the presence of specific antigens in its capsule that are shared with nerves. Immune responses directed against capsular lipopolysaccharides produce antibodies that cross-react with myelin to cause demyelination. C jejuni infections demonstrate significant association with antibodies against gangliosides GM1 and GD1b. Although GM1 antibodies can be found with demyelinating GBS, GM1 antibodies are more common in the axonal and inexcitable groups. Even in the subgroup of patients with GM1 antibodies, however, the clinical manifestations vary. Host susceptibility is probably one determinant in the development of GBS after infectious illness.

Cytomegalovirus (CMV) infections are the second most commonly found infections preceding GBS; they account for the most common viral triggers of GBS. The Dutch Guillain-Barré study found CMV to be present in 13% of patients. CMV infections present as upper respiratory tract infections, pneumonias, and nonspecific flulike illnesses. GBS patients with preceding CMV infections often have prominent involvement of the sensory and cranial nerves. CMV infections are associated significantly with antibodies against the ganglioside GM2.

Other significant, although less frequently identified, infectious agents in GBS patients include Epstein-Barr virus (EBV), Mycoplasma pneumoniae, and varicella zoster virus. The association of GBS and human immunodeficiency virus (HIV) also is well recognized. Infections with Haemophilus influenzae, parainfluenza 1 virus, influenza A virus, influenza B virus, adenovirus, and herpes simplex virus all have been demonstrated in patients with GBS, although not more frequently than in controls.

Events such as surgery, trauma, and pregnancy have been reported as possible triggers of GBS, but this association remains mostly anecdotal in the medical literature. Vaccinations also have been linked to GBS by temporal association, but no definite causal relation has been established in most cases, with the exception of the rabies vaccine prepared from infected brain tissues and the swine flu influenza vaccine administered in 1976-1977. Subsequent surveys have found no significantly increased incidence of GBS after vaccination programs.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Poliomyelitis
Nutritional neuropathies
Toxic neuropathies (eg, arsenic, thallium, organophosphates, lead)
Multifocal motor neuropathy
Mononeuritis multiplex
Critical illness polyneuropathy
Botulism
Vasculitic neuropathies
Diphtheritic polyneuritis
Acute myasthenia gravis
Tick paralysis
Lyme disease
Paralytic shellfish poisoning
Porphyria polyneuropathy
Chronic inflammatory demyelinating polyneuropathy
Acute myelopathy (eg, from compression, transverse myelitis, vascular injury)
Basilar artery thrombosis or embolism (locked-in syndrome)
Periodic paralysis
Hypophosphatemia
Metabolic myopathies
Polymyositis
Paraneoplastic neuropathy
Relapsing inflammatory polyneuropathy
Neoplastic meningitis
Leptomeningeal carcinomatosis
Conversion disorder/hysterical paralysis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CSF studies
• • During the acute phase of GBS, the characteristic findings include albuminocytologic dissociation, which is an elevation in CSF protein (>0.55 g/L) without an elevation of white blood cells ( <10 lymphocytes/µL).
  • The increase in CSF protein is thought to reflect the widespread inflammatory disease of the nerve roots.
• Basic laboratory studies, such as complete blood counts and metabolic panels, are of limited value in the diagnosis of GBS. They often are ordered, although, to exclude other infectious or metabolic causes of the weakness.
• Basic peripheral neuropathy workup is recommended in cases in which the diagnosis is uncertain. These studies may include thyroid panel, rheumatology profiles, vitamin B-12, folic acid, hemoglobin A1C, erythrocyte sedimentation rate (ESR), rapid protein reagent, immunoelectrophoresis of serum protein, and tests for heavy metals. Ordering of specific tests should be guided by the patient's history and presentation.
• Serologic studies are of limited value in the diagnosis of GBS.
• • An increase in titers for infectious agents such as CMV, EBV, or Mycoplasma may help in establishing etiology for epidemiologic purposes.
  • HIV has been reported to precede GBS, and serology should be tested in high-risk patients to establish possible infection with this agent.
• Serum autoantibodies are not measured routinely in the workup of GBS, but results may be helpful in patients with a questionable diagnosis or a variant of GBS.
• • Antibodies to glycolipids are observed in the sera of 60-70% of patients with GBS during the acute phase, with gangliosides being the major target antigens.
  • Antibodies to GM1 frequently are found in the sera of patients with GBS, both motor axonal neuropathy and AIDP variants. Antecedent C jejuni infections are associated closely with elevated titers of anti-GM1 antibodies.
  • Anti-GQ1b antibodies are found in patients with GBS with ophthalmoplegia, including patients with the Miller-Fisher variant.
  • Other antibodies to different major and minor gangliosides also have been found in GBS patients.

Imaging Studies

• MRI
• • Although nonspecific, MRI can reveal nerve root enhancement.
  • Imaging studies such as MRI or computed tomography (CT) scan of the spine may be more helpful in excluding other diagnoses, such as mechanical causes of myelopathy, than in assisting in the diagnosis of GBS.

Other Tests

• Electromyography
• • Electromyography (EMG) studies can be very helpful in the diagnostic workup of patients with suspected GBS. Abnormalities in the NCS consistent with demyelination are sensitive and represent specific findings for classic GBS.
  • Although NCS results classically show a picture of demyelinating neuropathy in most patients, other electrophysiologic subgroups include axonal and inexcitable groups. The inexcitable studies may represent either axonopathy or severe demyelination with distal conduction block.
  • Although most patients exhibit sensory abnormalities on NCS, these findings are much less marked than in motor nerves.
  • On NCS, demyelination is characterized by nerve conduction slowing, prolongation of the distal latencies, prolongation of the F-waves, conduction block, and/or temporal dispersion. Changes on NCS should be present in at least 2 nerves in regions not typical for compressive mononeuropathies, preferentially in anatomically distinct areas (eg, an arm and a leg, a limb and the face).
  • The needle examination is of limited value in GBS. Reduced motor unit recruitment and absent denervation help support suggestion of a demyelinating mechanism, although the same changes can be observed in early axonal damage with pending Wallerian degeneration. Denervation changes may be observed later in the disease course with severe cases.
  • In the axonal variant of the disease, absent or markedly reduced distal compound muscle action potentials (CMAP) are observed on NCS. On needle examination, profuse and early denervation potentials also support the conclusion that there has been axonal injury.
• Pulmonary function tests
• • Maximal inspiratory pressures and vital capacities are measurements of neuromuscular respiratory function and predict diaphragmatic strength. Maximal expiratory pressures also reflect abdominal muscle strength. Frequent evaluations of these parameters should be performed at bedside to monitor respiratory status and the need for ventilatory assistance.
  • Respiratory assistance should be considered when the expiratory vital capacity decreases to <18 mL/kg or there is a decrease in oxygen saturation (arterial PO₂ <70 mm Hg).

Procedures

• Lumbar puncture for CSF studies is recommended.

Histologic Findings

Lymphocyte and macrophage infiltration is observed on microscopic examination of peripheral nerves. Macrophage influx is believed to be responsible for the multifocal demyelination seen in GBS. A variable degree of Wallerian degeneration also can be observed with severe inflammatory changes. Cellular infiltrates are scattered throughout the cranial nerves, nerve roots, dorsal root ganglions, and peripheral nerves.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Rehabilitation Program

Physical Therapy

Estimates suggest that approximately 40% of patients hospitalized with GBS require inpatient rehabilitation. Unfortunately, no long-term rehabilitation outcome studies have been conducted, and treatment often is based on experiences with other neurologic conditions. The goals of the therapy programs are reducing the functional deficits and targeting the impairments and disabilities resulting from GBS.

Early in the acute phase of the disease course, patients may not be able to participate fully in an active therapy program. At that stage, patients benefit from daily range of motion (ROM) exercises and proper positioning to prevent muscle shortening and joint contractures. Addressing upright tolerance and endurance also may be a significant issue during the early part of rehabilitation. Active muscle strengthening then can be introduced slowly and may include isometric, isotonic, isokinetic, or progressive resistive exercises. Mobility skills, such as bed mobility, transfers, and ambulation, are targeted functions. Patients should be monitored for hemodynamic instability and cardiac arrhythmias, especially upon initiation of the rehabilitation program. The intensity of the exercise program also should be monitored, as overworking the muscles, paradoxically, may lead to worsening weakness.

Occupational Therapy

Occupational therapy professionals should be involved early in the rehabilitation program to promote upper body strengthening, ROM, and activities to promote functional self-care. Both restorative and compensatory strategies can be used to promote functional improvements. Energy conservation techniques and work simplification also may be helpful, especially if the patient demonstrates poor strength and endurance.

Speech Therapy

Speech therapy is involved to work on safe swallowing and speech skills for patients with significant oropharyngeal weakness, with resultant dysphagia and dysarthria. In ventilator-dependent patients, alternative communication strategies also may need to be implemented. Once weaned from the ventilator, patients with tracheostomies can learn voicing strategies and eventually can be weaned from the tracheostomy tube. Cognitive screening also can be performed conjointly with neuropsychology to assess for deficits, as cognitive problems have been reported in some patients with GBS, especially patients after an extended stay in the intensive care unit (ICU).

Recreational Therapy

Participation in recreational therapy assists in the patient's adjustment to disability and improves integration into the community. Recreational activities, either new or adapted, can be used to promote growth, development, and independence of the often long-term hospitalized patient.

Medical Issues/Complications

Good supportive care is critical in the treatment of patients with GBS. As most deaths related to GBS are associated with complications of ventilatory failure and autonomic dysfunction, many patients with GBS need to be monitored closely in ICUs by physicians experienced in acute neuromuscular paralysis and accompanying complications. Competent intensive care includes such things as respiratory therapy, cardiac monitoring, safe nutritional supplementation, and monitoring for infectious complications such as pneumonia, urinary tract infections, and septicemia.

Approximately one third of patients with GBS require ventilatory support. Monitoring for respiratory failure, bulbar weakness, and difficulties with swallowing help to anticipate complications. Proper positioning of the patient to optimize lung expansion and secretion management for airway clearance is required to minimize respiratory complications. Serial assessment of ventilatory status is needed, including measurements of vital capacity and pulse oximetric monitoring. Respiratory assistance should be considered when the expiratory vital capacity decreases to <18 mL/kg or a decrease in oxygen saturation is noted (arterial PO₂ < 70 mm Hg).

Close monitoring of heart rate, blood pressure, and cardiac arrhythmias allows early detection of life-threatening situations. Critically ill patients require continuous telemetry and close medical supervision in an ICU setting. Antihypertensives and vasoactive drugs should be used with caution in patients with autonomic instability.

Enteric or parental feedings are required for patients on mechanical ventilation to ensure that adequate caloric needs are met when the metabolic demand is high. Even patients off the ventilator may require nutritional support if dysphagia is severe. Precautions against dysphagia and dietary manipulations should be used to prevent aspiration and subsequent pneumonias in patients at risk.

Prevention of secondary complications of immobility, such as deep venous thrombosis (DVT), pressure sores, and development of contractures, also is required. This preventative action entails careful positioning, frequent postural changes, and daily ROM to prevent the latter 2 complications. Subcutaneous heparin and thromboguards often are used in the treatment of immobile patients to prevent lower extremity DVTs and secondary pulmonary embolisms (PE). Pain management with analgesics and adjunct medications also may be needed. Modalities such as transcutaneous electrical nerve stimulation (TENS) and heat may be of benefit in the management of complaints of myalgia. Desensitization techniques can be used to improve the patient's tolerance for activities.

Although bowel and bladder dysfunction is generally transitory, management of these functions is needed to prevent other complications. Initial management should be directed toward safe evacuation and prevention of overdistension. Monitoring for secondary infections, such as a urinary tract infection, is also an area of concern.

Hospitalized patients with GBS may experience mental status changes, including hallucinations, delusions, vivid dreams, and sleep abnormalities. These occurrences are thought to be associated with autonomic dysfunction and are more frequent in patients with severe symptoms. The issue resolves as the patient recovers.

Surgical Intervention

Tracheotomy may be required in the patient with prolonged respiratory failure, especially if mechanical ventilation is required for more than 2 weeks. Percutaneous feeding tubes also may be required to meet the nutritional needs of patients with severe and prolonged dysphagia. A central venous line needs to be placed for patients undergoing plasmapheresis.

Consultations

• Consultation with a neurologist can be helpful in the initial diagnosis, workup, and treatment of patients admitted to the medical floor with GBS.
• Critical care specialists may be required for patients in the ICU to help manage respiratory failure and multiple medical complications.
• Consultation with a pulmonologist may be needed to perform workup and manage respiratory issues such as acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure.
• Consultation with a cardiologist may be required if significant cardiovascular complications, such as labile blood pressure and cardiac arrhythmias, arise from the associated autonomic dysfunction.
• Consultation with a surgeon may be required for placement of tracheostomies, enteral feeding tubes, and central lines.
• Physical medicine and rehabilitation specialists should evaluate patients for impairments and disabilities arising from the disease and help determine the most appropriate setting and intensity of rehabilitation care.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Immunomodulatory therapy, such as plasmapheresis or intravenous immunoglobulin (IVIG), is frequently used in GBS patients. The efficacy of plasmapheresis and IVIG appears about equal in shortening the average duration of disease. Combined treatment has not shown further statistically significant reduction of disability. The decision to use immunomodulatory therapy is based on the severity of the disease, rate of progression, and length of time between the first symptom and presentation. Risks such as thrombotic events associated with IVIG should be taken into consideration. Patients with rapidly progressive severe disease are most likely to benefit from treatment, with improvements in the rate of functional recovery.

Drug Category: Immunomodulatory agents

To improve clinical and immunologic aspects of the disease. May decrease autoantibody production and increase solubilization and removal of immune complexes.

Drug Name	Plasma exchange or plasmapheresis
Description	The mechanism of plasmapheresis is the removal of immunoglobulins and antibodies from the serum by removing the blood from the body, separating cells from the plasma, and replacing the cells in fresh frozen plasma, albumin, or saline.
Adult Dose	3-5 exchanges of 50 mL/kg of plasma IV over 1-2 wk via central venous catheter suggested
Pediatric Dose	Administer as in adults
Contraindications	Septicemia, active bleeding, and severe cardiovascular instability
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Plasma exchange requires skilled personnel and specialized equipment that may not be available in all hospitals; in theory, plasma exchange may increase the risk of infection and hemorrhage due to the removal of immunoglobulins and clotting factors; complications and side effects from plasma exchange include hypotension, septicemia, pneumonia, cardiac arrhythmias, malaise, hypoprothrombinemia with bleeding/abnormal clotting, and hypocalcemia

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• GBS treatment requires careful and intensive care to monitor for complications such as respiratory difficulties and autonomic dysfunction. Approximately one third of patients require admission to the ICU, primarily due to respiratory failure. After medical stabilization, patients can be treated on a general medical/neurologic floor, but continued vigilance remains important in preventing respiratory, cardiovascular, and other medical complications. Continued care also is needed to minimize problems related to immobility, neurogenic bowel and bladder, and pain. Early involvement of allied health staff is recommended.

Further Outpatient Care

• Although follow-up studies generally have assessed patients 6-12 months after onset, some studies have reported continued improvements in strength even beyond 2 years. With prolonged recovery possible, GBS patients with continued neurologic deficits may benefit from ongoing physical therapy and conditioning programs.
• Numerous papers have addressed the issue of persistent fatigue after recovering from GBS. Studies have suggested that a large percentage of patients continue to have problems related to fatigue, subsequently limiting their function at home, work, and during leisure activities. Treatment suggestions range from gentle exercise to prescribing medications traditionally used to stimulate initiation. Effectiveness of various interventions continues to be studied.
• GBS can produce long-lasting changes in the psychosocial status of patients and families. Changes in work and leisure activities can be observed in just over one third of these patients, and psychosocial functional health status can be impaired even years after the GBS event. Interestingly, psychosocial performance does not seem to correlate with the severity of residual physical function. Poor conditioning and easy fatigability may be contributory factors. Therefore, providing long-term attention and support for this population group is important.

In/Out Patient Meds

• Immunomodulatory medications have been used to hasten recovery. The efficacy of IVIG in GBS patients has been shown to equal that of plasma exchange in well-controlled clinical trials. IVIG is easier to implement and potentially safer, and use of IVIG versus plasma exchange may be a choice of availability and convenience. Oral and intravenous steroids have been tried in GBS without any clinical benefit and are not used currently in the treatment of GBS.
• Hemodynamic changes related to autonomic dysfunction usually are transitory, and patients rarely require long-term medications to treat blood pressure or cardiac problems.
• Pain medications may be required in both the inpatient and outpatient settings. A tiered pharmacologic approach starting with nonsteroidal anti-inflammatory drugs or acetaminophen and then adding narcotic agents as needed usually is recommended. Most patients do not required narcotic analgesics after the first couple of months of illness. Adjunct medications for pain, such as tricyclic antidepressants and certain anticonvulsants, also may be beneficial for dysesthetic-type pains.
• Anticoagulants, such as heparin or low molecular weight heparin, are recommended to prevent thromboembolic disease in the sedentary patient.

Transfer

• Patients may require transfer to the ICU if serious respiratory or cardiac problems occur. Upon medical and neurologic stabilization, patients may require transfer to an inpatient rehabilitation unit if functional impairments persist.

Deterrence

• C jejuni is the most common cause of bacterial gastroenteritis in developed countries and also is the organism most frequently identified in association with GBS. Preventive measures to control C jejuni infections, such as vaccinations, may be the best means to prevent GBS.

Complications

• A small percentage (~10%) of patients have an acute relapse after initial improvement or stabilization after treatment. Some patients also demonstrate treatment fluctuations during their clinical course. Though both procedures are controversial, there is no convincing evidence that either IVIG or plasma exchange has a significant effect on the rate of treatment failure or acute relapses. The risk of relapse does appear to be higher in patients with a later onset of treatment, a more protracted disease course, and more associated medical conditions. Additional treatments of plasma exchange or IVIG often result in further improvement.

Prognosis

• Although most patients with GBS make good recovery, 2-12% die from complications related to GBS, and a significant percentage of survivors have persistent motor sequelae. Estimates indicate that 75-85% of patients experience good recovery, 15-20% have moderate residual deficits, and 1-10% are left severely disabled. Although the exact prevalence is uncertain, up to 25,000-50,000 persons in the United States may have long-term functional deficits from GBS.
• Older age, poor upper extremity (UE) muscle strength, the need for mechanical ventilation, Medical Research Council (MRC) scores of less than 40, and preceding gastrointestinal infections all have been found to have an adverse effect on outcomes associated with GBS. A rapidly progressive onset of weakness also has been associated with less favorable outcomes in many studies, though delayed time to peak disability has been shown to be an independent predictor of poor outcome at 1 year in other studies. Low mean CMAP amplitudes of less than 20% of the lower limit of normal or the presence of inexcitable nerves on initial electrophysiologic studies are other predictors of poorer functional outcomes. Persistence of a low mean CMAP on later testing (>1 mo after onset) results in an even higher sensitivity and specificity of testing than the initial test after onset. The sex of the patient, the presence of underlying pulmonary disease, or manifestation of dysautonomia has no prognostic significance.
• The speed of recovery varies. Recovery often takes place within a few weeks or months; however, if axonal degeneration has occurred, recovery can be expected to progress slowly over many months as regeneration may require 6-18 months. In general, slower and less complete recovery is observed in older patients.

Patient Education

• Patients with GBS and their families should be educated on the illness, disease process, and anticipated course. GBS is a life event with a potentially long-lasting influence on patients' physical and psychosocial well-being. Family education and training also is recommended to prevent complications during the early stages of the disease and to assist in the recovery of function during the rehabilitation stages.
• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Guillain-Barré Syndrome.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Patients diagnosed with GBS should be admitted into the hospital for close monitoring until it has been determined that the course of the disease has reached a plateau or even undergone reversal. Though the weakness initially may be mild and nondisabling, symptoms can progress rapidly over just a few days. Continued progression may result in a neuromuscular emergency with profound paralysis, respiratory insufficiency, and/or autonomic dysfunction with cardiovascular complications. Early recognition and treatment of GBS also may be important in the long-term prognosis, especially in the patient with poor clinical prognostic signs such as older age, rapid progressive course, and antecedent diarrhea.

Special Concerns

• Immunotherapy for children with GBS has not been studied rigorously with randomized well-controlled studies. Despite this fact, immunotherapy is used standardly in the pediatric patient with GBS.
• Immunotherapy for pregnant women has not been studied, and safety for use during pregnancy has not been established.
• Older age is a risk factor for less favorable prognosis. Recovery often is slower and less complete in elderly patients. Mortality rates also are higher than in younger patients.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Jun 7, 2006