Guillain-Barre Syndrome

GENERAL PRINCIPLES

Definition

Guillain-Barre syndrome (GBS) is an acute polyradiculoneuropathy syndrome and a common cause of acute flaccid paralysis. There are many GBS subtypes with marked geographic variability in their prevalence.

Classification

• The acute immune/inflammatory demyelinating polyneuropathy (AIDP) variant is the most common GBS variant in North America. It is an acute immune-mediated polyneuropathy/radiculopathy with presumed autoantibodies (as yet unidentified) directed against myelin antigens.

• Axonal variants of GBS include acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy, acute motor conduction block neuropathy (AMCBN), Miller Fisher syndrome (MFS), and pharyngeal-cervical-brachial (PCB) weakness. Many of these syndromes are associated with antiganglioside antibodies directed against gangliosides located in the axolemma near the nodes of Ranvier. These axonal variants are much more common in Japan, China, and third-world countries than they are in the US. Antibody associations include:

ξ IgG anti-GM1 antibodies in AMAN and AMCBN

ξ IgG anti-GQ1b and less commonly IgG anti-GT1a in MFS, a syndrome consisting of ophthalmoparesis, ataxia, and areflexia

ξ IgG anti-GT1a and less commonly IgG anti-GQ1b in PCB weakness syndrome.

Pathophysiology

• GBS results from an attack of peripheral myelin or axons mediated by autoantibodies originally generated in response to an infection that typically precedes the onset of neuropathy symptoms by days to weeks. These antibodies cross-react with the myelin or nodal axolemma anti gens via molecular mimicry.

• This concept is well established in the axonal variants where there is definitive evidence of molecular mimicry between Campylobacter jejuni lipooligosaccharides and the ganglioside antigens listed above.

• This concept is less well established in other AIDP variants, given the absence of a known autoantibody/myelin antigen. Prodromal infections commonly associated with AIDP include cytomegalovirus and Epstein-Barr virus.

DIAGNOSIS

Clinical Presentation

• AIDP typically presents with progressive, symmetric ascending paralysis.

• Mild asymmetries are common, but major asymmetries are a red flag suggestive of an alternative diagnosis.

• Reflexes are almost always hypoactive or absent. Exceptions exist, especially with the axonal variants (in particular with Fisher-Bickerstaff syndrome, which has elements of MFS along with hypersomnolence in the setting of concurrent brainstem encephalitis).

• Sensory symptoms, such as paresthesias in the hands and feet, are often present, but objective sensory loss is uncommon.

• Facial and/or oropharyngeal weakness occurs in about 70% of AIDP patients.

• Respiratory failure, necessitating intubation, occurs in 25%-30% of patients.³⁴

• Pain in the back, hips, and thighs is common. Pain is one of the most common presenting symptoms of GBS in the pediatric population.

• Autonomic instability is common (approximately 60%) and potentially life threatening. Common manifestations include tachycardia/bradycardia, hypotension alternating with hypertension, and ileus.

Differential Diagnosis

See Table 27-11.

TABLE 27-11

DIFFERENTIAL DIAGNOSIS OF ACUTE IMMUNE DEMYELINATING POLYNEUROPATHY

• AcuteZinitial presentation of chronic inflammatory demyelinating polyneuropathy

• ParaproteinemicZparaneoplastic PpolyradiculopathyZpolyneuropathy

• DiabeticZnondiabetic lumbosacral radiculoplexopathies

• Sarcoidosis

• Mononeuritis multiplex (confluent)

• West Nile and polioviruses (usually has fever, CSF pleocytosis, and often asymmetric paralysis)

• HIV

• Lyme disease (if in endemic area)

• Postdiphtheric paralysis

• Tick paralysis and other neurotoxins

• Myasthenia gravis (MFS variant)

• Critical illness myopathy

• Prolonged neuromuscular junction blockade

• Periodic paralysis

• Thiamine deficiency (MFS variant in particular)

• Botulism

• Arsenic

• Lead

• Chemotherapy

• Acute intermittent porphyria

• Carcinomatous or lymphomatous meningitis with root involvement

• Functional WeaknessZconversion disorder

See http:ZZneuromuscular.wustl.eduZtimeZnmacute.htm for further information. CSF, cerebral spinal fluid; MFS, Miller Fisher syndrome variant of Guillain-Barre Syndrome (associated with ataxia, areflexia, and ophthalmoparesis).

Diagnostic Testing

IMAGING

MRI of the spine is indicated in atypical cases or in those with concern for one of the differentials listed earlier that could result in a myeloradiculopathy. Nerve root contrast enhancement and/or thickening can be seen with GBS.

DIAGNOSTIC PROCEDURES

• LP should be performed to narrow the differential and evaluate for albuminocytologic

dissociation.

• CSF protein is usually elevated about 1 week after symptom onset. It may be normal if checked earlier (e.g., 85% of patients with normal CSF within first 2 days).

• CSF leukocytosis is uncommon, and if present (especially gt;25 cells#8725;#956;L), an alternative diagnosis should be considered.

• Nerve conduction studies (NCS) and electromyography (EMG) are a very important part of the evaluation but should not delay initiation of treatment, particularly in severe cases. NCS should include evaluation of the proximal nerve segments via “late” responses (F waves and H reflexes). EMG-NCS performed early in the disease course may have very few abnormalities and can even be normal but serves an important role in the diagnostic evaluation, even when normal. A repeat study after a few weeks can be extremely useful for classification and prognostication, particularly when there is a baseline study available for comparison.

TREATMENT

• Follow respiratory function closely, including oximetry and frequent bedside measurements of vital capacity (VC) and negative inspiratory force (NIF).

• We use the “20/30” rule in identifying patients who will likely require ventilatory support: lt;20 mL/kg of forced VC (FVC) (approximately 1.5 L for an average-size adult) and an NIF gt;-30 cm H₂O. These parameters provide a more sensitive measure for impending respiratory failure than do the presence of hypoxia, dyspnea, and acidosis. The threshold for elective intubation should be low.

• If NIF/FVC testing is not available at the bedside, a quick and indirect measure is to ask the patient to count to as high a number as possible on one breath.

• Paroxysmal hypertension should not be treated with antihypertensive medications unless absolutely necessary (e.g., signs of end-organ injury or comorbid coronary artery disease). If necessary, extremely low doses of titratable short-acting agents are preferred.

• Hypotension is usually caused by decreased venous return and peripheral vasodilation. Mechanically ventilated patients are particularly prone to hypotension. Treatment consists of intravascular volume expansion; occasionally, vasopressors may be required (see Chapter 8, Critical Care).

• Continuous telemetry monitoring is necessary to monitor for cardiac arrhythmias.

• Prevention of exposure keratitis of the eye, venous thrombosis, and vigilance for hyponatremia, including syndrome of inappropriate diuretic hormone, should be priorities.

Medications

• Plasma exchange (PLEX) and IVIG are comparably effective in improving outcomes and shortening duration of disease when administered early to patients who cannot walk or have respiratory failure.³⁵ The decision between the two depends on the individual patient's comorbidities and medical history.

• Corticosteroids are not indicated and may actually delay recovery.

• Neuropathic pain medications may be needed.

Nonpharmacologic Therapies

Physical therapy to prevent contractures and improve strength and function should be started early.

Complications

Complications from prolonged hospitalization and ventilation may occur. These include aspiration pneumonia, sepsis, pressure ulcers, and pulmonary embolism.

Prognosis

• The disease typically progresses over 2-4 weeks, with all patients, by definition, reaching their nadir by 4 weeks, followed by a plateau of several weeks.

• Recovery takes place over months.

ξ Overall, about 80% of patients recover completely or have only minor deficits.

• About 5% of the patients die due to respiratory or autonomic complications despite optimal medical therapy.