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

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.

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.

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 jejuniinfection, 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

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