Chapter 195

Guillain-Barré Syndrome

Seth Kolkin

Definition and Epidemiology

Guillain-Barré syndrome (GBS) is a group of acute monophasic immune-mediated peripheral neuropathies. Initially GBS referred only to a demyelinating neuropathy, but now acute inflammatory demyelinating polyradiculoneuropathy (AIDP) accounts for 85% to 90% of GBS in North America and Europe. Other subtypes include the Miller Fisher syndrome (MFS), in which oculomotor nerve myelin is affected, or axonal variants in which the axon rather than the myelin sheath is targeted. Axonal variants of GBS are more common in some populations around the world—for example, nearly 40% of GBS in Japan and Mexico and 75% in China.¹^–⁶ Although the syndrome was initially described by Landry in 1859 and then Strohl, Barré, and Guillain in 1916, awareness was heightened when a cluster of cases followed mass vaccinations for swine influenza in 1976. There has not been a clear association between subsequent vaccination programs and GBS.⁷

Patients with GBS usually develop weakness over several days to weeks, and when weakness is accompanied by respiratory weakness and/or autonomic instability, patients can become critically ill. Up to 5% die despite intensive care unit (ICU) care, and about 20% of patients have residual weakness a year later.¹ The incidence of GBS is between 1 and 2 per 100,000.⁵ Relapses occur in 5% to 10% of patients, on average 7 years after the initial attack.

Pathophysiology

Two thirds of the time, GBS follows an upper respiratory or gastrointestinal infection by 1 to 4 weeks. The most commonly identified viruses are cytomegalovirus (CMV) and Epstein-Barr virus, and bacteria include Campylobacter jejuni (23% to 45%), Mycoplasma pneumoniae (5%), and Haemophilus influenzae. However, the risk of GBS after C. jejuni infection is less than 1 : 1000, and between 1 and 2 per 1000 after CMV, so host factors are presumed to play a role as well.⁵ Molecular mimicry—the immune system’s antibody response recognizing components of the host’s peripheral nerve—is thought to be the cause of GBS. This has been best characterized in some acute motor axonal neuropathy (AMAN) patients with C. jejuni infection in which antibodies directed at the lipo-oligosaccharide coating of the bacteria cross-react with gangliosides (GM1 and GD1a) on the axon in the node of Ranvier.⁶ In addition, patients with MFS have antibodies directed against the GQ1b ganglioside, which is in spinal nerve root and cranial nerve paranodal myelin.⁸ Most recently, serum autoantibodies against moesin (membrane-organizing extension spike protein) on the myelinating Schwann cells have been identified in AIDP patients after CMV infection.⁹ Once bound, those antibodies cause an influx of T lymphocytes and macrophages and activate membrane attack complex, thus damaging the nerve myelin or axon.

Clinical Presentation

Patients develop the onset of relatively symmetric paresthesias and/or weakness, typically starting in the lower extremities and evolving over hours to days. Frequently there is a history of an antecedent infection. They often have back pain but do not have bowel or bladder dysfunction early in the course. The weakness can spread to involve the upper extremities then the respiratory muscles and finally can progress to complete paralysis. The weakness typically peaks in about 3 weeks, at which point 25% of patients have respiratory insufficiency and two thirds are unable to walk independently.

Patients with AMAN, as opposed to AIDP, can have preserved reflexes and tend not to have pain.

Patients with MFS will have ophthalmoplegia, ataxia, and areflexia and can also have distal paresthesias. Their syndrome peaks in 1 week, and these patients tend to recover more quickly and completely.⁸

Physical Examination

Even though sensory symptoms are typical, sensory findings on examination are usually absent. Progressive weakness, almost always with an evolving loss of deep tendon reflexes, is typical of GBS. Patients with respiratory muscle weakness have decreased breath sounds and a weakened cough, reduced vital capacity on bedside spirometry, and neck muscle weakness. In addition, autonomic instability can cause wide fluctuations in pulse rate and blood pressure, urinary retention, and bowel dysmotility.

On examination, MFS patients have incoordination in the extremities and weakness of eye movements with double vision.

Diagnostics

After the presence of true weakness has been confirmed, the neurologic examination is essential to determine which component(s) of the nervous system are involved—brain, spinal cord, peripheral nerve, neuromuscular junction, and/or muscle.

• Lesions in the brain usually cause unilateral weakness and are often associated with other neurologic signs and symptoms (e.g., involving the cranial nerves or cognition).

• A sensory level on the torso, bowel or bladder involvement, increased deep tendon reflexes, and/or a Babinski sign would suggest spinal cord pathology rather than the peripheral nerve dysfunction of GBS.

Screening for a systemic infection or organ dysfunction is based on the history and accompanying abnormalities on the general physical examination, complete blood count (CBC), and complete metabolic profile (CMP). Liver transaminases are elevated in 40% of patients and, because of syndrome of inappropriate antidiuretic hormone (SIADH), serum sodium is reduced in 25%.¹

If GBS is suspected, lumbar puncture is the most important confirmatory laboratory test.

• Classically, there is albuminocytologic disassociation—that is, an elevated cerebrospinal fluid (CSF) protein with minimal if any increase of mononuclear CSF white blood cells (<10/mL³). However, that pattern might not be seen during the first week of illness.¹^–⁴

• Acutely, the spinal fluid might show polymorphonuclear leukocytes (PMNs) without an elevated protein level but often converts to the typical pattern in a few days.

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