Guillain-Barré syndrome (GBS) is a collection of clinically related disorders characterized by acute-onset monophasic inflammation of the peripheral nervous system. Affected individuals typically present with ascending weakness and loss of reflexes over days to weeks. Paresis or even plegia may involve the limbs, face, eyes, or respiratory muscles. Autonomic and sensory disturbances, including numbness and pain, are frequently present. Neurologic deficits usually peak by 4 weeks. Presentations include the most common form, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), as well as acute motor axonal neuropathy, Miller Fisher syndrome, and other variants.
GBS is the most common cause of acute or subacute flaccid weakness worldwide. The annual incidence is as high as 1.34 cases per 100,000 in individuals <15 years of age, with a slight male predominance. AIDP is the most common form, accounting for up to 90% of cases in North America, with Miller Fisher syndrome being the next most common variant presentation.
- Up to two thirds of cases are preceded by a mild upper respiratory or gastrointestinal tract illness in the weeks prior to the onset of symptoms.
- Campylobacter jejuni enteritis is the most common bacterial infection associated with developing GBS.
- Viral exposures associated with the development of GBS include cytomegalovirus (CMV), Epstein-Barr virus, varicella-zoster virus, acute HIV infection, influenza A, H1N1 influenza, enterovirus, Zika virus, and others.
- Pregnancy, certain cancers, and recent surgery or vaccination have also been associated with GBS.
- Often, no precipitating exposure can be identified.
Polymorphisms in the immunoglobulin Kappa light chains and in TNF-α have been associated with a higher rate of GBS in the setting of antecedent infection with C. jejuni. The majority of GBS cases do not demonstrate a clear genetic inheritance pattern. PMP22 gene (601097) on chromosome 17 was identified in a single family with the acute (AIDP) and chronic (CIDP) forms of inflammatory demyelinating polyneuropathy.
Inflammatory cell–mediated and humoral-mediated immune mechanisms play a role in segmental demyelination on nerve biopsy; lymphocytes and macrophages participate in myelin destruction. Axonal variants of GBS feature axonal degeneration without demyelination. Circulating antiganglioside antibodies (e.g., GM1, GD1a, GM2, GQ1b) found in particular subtypes suggest a molecular mimicry mechanism stimulated by infection. Some variants (e.g., Bickerstaff encephalitis) involve central and peripheral demyelination.
Molecular mimicry is believed to underlie cases of GBS associated with a preceding infection.
Commonly Associated Conditions
- GBS most commonly affects previously healthy individuals.
- GBS is seen in a higher than expected rate in patients with sarcoidosis, systemic lupus erythematosus, lymphoma, HIV infection, Lyme disease, and solid tumors.
- GBS has a variety of clinical presentations; a high index of suspicion is critical. Typical features are distal sensory changes followed by progressive motor weakness and areflexia.
- Common presentations include decreased ambulation or crawling in infants, unsteady gait which may be due to sensory ataxia, facial weakness, diplopia, leg or back pain, or sensory changes in the extremities.
- Paresthesia and pain typically occur in a stocking/glove distribution, frequently early in the course.
- Most patients first note leg weakness or gait instability that progresses over days to weeks. 60% are unable to walk at the peak of symptoms.
- Patients may also report shortness of breath, palpitations, light-headedness, constipation, or urinary retention secondary to respiratory and autonomic involvement.
- Two thirds of patients will report an infectious illness 2 to 3 weeks prior to symptom onset. Consider direct infection (e.g., poliomyelitis, West Nile virus) if fever is present at symptom onset.
- Characteristic findings include muscular weakness and sensory changes, most often symmetric with distal greater than proximal involvement. Proximally, predominant symptoms do not preclude the diagnosis but rather may indicate radicular involvement.
- Deep tendon reflexes are usually diminished or absent within 1 week of symptom onset.
- Respiratory muscle weakness may make assessment of respiratory insufficiency or failure, difficult on physical examination. Careful physical assessment, combined with diagnostic procedures such as measurement of vital capacity or maximum inspiratory pressure, are essential, as upper airway or ventilatory compromise may progress rapidly.
- Respiratory failure leads to intubation in up to 20% of patients. Bulbar weakness and poor airway protection may also necessitate intubation.
- Impending respiratory failure can often be unpredictable, and hypercarbia on blood gas and desaturation are late findings.
- Bilateral facial weakness occurs in up to 50% of cases.
- Ophthalmoplegia, ataxia, and areflexia are the characteristic features of Miller Fisher syndrome.
- Neonates and infants may (rarely) present as floppy infants.
- Myasthenia gravis
- Intoxication (e.g., heavy metals, organophosphates)
- Infection: poliomyelitis, West Nile virus, CMV, HIV, Lyme disease, diphtheria, botulism
- Acute cerebellar ataxia (sometimes associated with neuroblastoma)
- Transverse myelitis
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Vasculitic neuropathy
- Severe vitamin B12 deficiency
- Metabolic abnormalities: hypermagnesemia, hypophosphatemia
- Porphyric neuropathy
- Acute presentations of inherited peripheral neuropathies
- Tick paralysis
- Conversion, psychogenic weakness, astasia/abasia
Diagnostic Tests and Interpretation
- In atypical cases, consider heavy metal screening, HIV testing, Lyme testing, porphyria screening, and acetylcholine receptor antibodies (myasthenia gravis).
- IgA level should be considered, particularly if there is a history of frequent pulmonary infections, as IgA deficiency can be associated with a higher risk of anaphylaxis to intravenous immunoglobulin (IVIG) therapy.
- MRI of the spine (with gadolinium enhancement), as spinal nerve root enhancement on MRI can support the diagnosis of GBS
- Lumbar puncture may demonstrate an albuminocytologic dissociation with an elevated protein and normal cell count after the 1st week of symptoms. Minimal pleocytosis (<50 cells/mL), largely mononuclear leukocytes, may occur but should prompt consideration of alternative etiology.
- Nerve conduction studies (NCS) and electromyography (EMG) can confirm diagnosis of GBS and are helpful when clinical, imaging, or CSF findings are ambiguous. NCS and EMG are abnormal in 50% of patients in the first 2 weeks and in 85% of patients afterward.
- Initially, needle EMG may be normal; consider serial studies if initially nondiagnostic.
- Initially, gait instability may mistakenly be interpreted as being psychogenic.
- Reflexes may be preserved in early stages of illness.
- Proximal symptoms may predominate early on.
- Check for reflexes in patients with bilateral Bell palsy.
- Respiratory failure necessitating intubation and mechanical ventilation may occur in up to 20% of affected children, may develop quickly, and is of a neuromuscular, rather than obstructive, nature. As such, work of breathing may not appear to be increased.
- Treat hypertension cautiously; catastrophic refractory hypotension may ensue.
- Regular monitoring of vital capacity and maximum inspiratory pressure, initially every 4 hours or more frequently if indicated. Consider ICU monitoring for patients with poor or declining respiratory function; strongly consider intubation if vital capacity reaches <50% of normal.
- Frequent heart rate and blood pressure assessments to monitor for autonomic dysregulation
- Bowel regimen and assessment for urinary retention
- Deep venous thrombosis (DVT) prophylaxis
- Swallowing evaluation
A combination of supportive therapy and immunotherapy is the mainstay of treatment for patients with GBS.
- IVIG and plasmapheresis are equally effective as 1st-line immunotherapy and are well-tolerated. Combining both therapies is not more effective than monotherapy. Complications and discontinuation of therapy are less common with IVIG.
- IVIG dosing:
- 2 g/kg of body weight, typically given as 0.4 g/kg/24 h for 5 consecutive days
- Alternate dosing regimens of 1 g/kg/24 h for 2 consecutive days or 2 g/kg as a single dose may be used.
- Plasmapheresis regimen:
- Total plasma exchange volume of 200 to 250 mL/kg divided in 3 to 5 treatments over 7 to 14 days
- Therapy initiation is recommended within 4 weeks of symptom onset for patients who cannot walk and within 2 weeks for patients who can.
- Plasmapheresis may be performed peripherally in children big enough for large-bore peripheral IV lines but requires placement of a central catheter in others.
- Corticosteroids are not helpful and are not recommended.
- Pain from nerve root inflammation is common in GBS and should be treated aggressively. Agents such as gabapentin can be useful.
Issue for Referral
Neurology follow-up typically 4 to 6 weeks after discharge
Physical therapy: Avoid contractures with lower extremity splinting and early passive range of motion. Aggressive physical and occupational therapy are essential for good outcomes.
- Hospitalization is often required to monitor for or manage progressive respiratory insufficiency, autonomic dysregulation, or neuropathic pain.
- Hospitalize patients whose symptoms progress over hours to days, who have any respiratory or bulbar complaints, or who are nonambulatory.
- Particular attention should be paid to preventing aspiration, skin breakdown, contractures, DVT, and secondary compressive neuropathies.
- Discharge criteria: completion of immunotherapy and stabilization of symptoms
- Consider intensive inpatient rehabilitation depending on the degree of neurologic impairment.
- Improvement typically begins 2 to 3 weeks after onset of symptoms up to 2 months in some patients.
- Improvement continues for up to 2 to 3 years.
Parent Internet information: Guillain-Barré Syndrome GBS/CIDP Foundation International: http://www.gbs-cidp.org/
- Most individuals recover, although 25% may have residual symptoms; ultimate functional recovery depends on the degree of axonal injury. Follow-up electrodiagnostic studies can be helpful in some cases.
- Early prognosticators include fulminant onset and the severity of weakness at the disease nadir.
- Overall prognosis in children is better than in adults.
- Complications include respiratory failure, blood pressure dysregulation (hypotension and/or hypertension), urinary retention, aspiration, pain syndromes, DVT with or without pulmonary embolism, and infection.
- Death occurs in up to 6% of cases, typically from early respiratory failure or autonomic instability.
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357.0 Acute infective polyneuritis
G61.0 Guillain-Barre syndrome
40956001 Guillain-Barre syndrome (disorder)
- Q: Is GBS contagious?
- A: No.
- Q: Will I get GBS again?
- A: Recurrent attacks occur in up to 5% of patients. Treatment-related fluctuations (worsening after completion of immunotherapy) occur in up to 16% of patients in the first 2 months. Finally, up to 5% of patients ultimately diagnosed with CIDP will present acutely and can be indistinguishable from GBS initially.
- Q: Do all cases require hospitalization and immunomodulatory treatment?
- A: Some youngsters with mild, nondisabling symptoms may be observed as outpatients (≤10%).
Sharon O. Wietstock, MD, MSc
Brett J. Bordini, MD
© Wolters Kluwer Health Lippincott Williams & Wilkins