Woman, 20, With Difficulty Walking

An example of this is the apparent cross-reaction of the ganglioside GM1 with C jejuni lipopolysaccharide antigens.^14,15 The resulting effect is immunologic damage to the peripheral nervous system. The flaccid paralysis that occurs in patients with GBS is thought to be caused by lymphocytic infiltration and complement activation of the spinal roots and peripheral nerves, where macrophages strip the myelin.^5,15,16

Stages and Variants
Three stages characterize the course of GBS. The acute phase, which lasts one to four weeks, begins with onset of symptoms and persists until the associated neurologic deterioration has ceased. During the second phase, the plateau period, symptoms persist with no further deterioration; this stage can last several days to several weeks or months. The final phase, the recovery period, can last from four months to two years after symptom onset.^15,17,18

The clinical course of GBS is highly variable and in many cases difficult to predict. Certain factors have been associated with a poor outcome: advancing age, previous presence of diarrhea, need for mechanical ventilation, an extended plateau phase, and a lower patient score on the Erasmus GBS Outcome Scale,¹⁹ when measured two weeks after GBS onset.^8,20 This score can help predict the patient’s chance of independent walking after six months.^15,19

Although the classic presenting symptom of GBS is symmetric ascending weakness, several disease variants have been identified, with differing symptoms and degrees of recovery. These variants also differ in terms of the muscle groups affected; in some, visual defects may be present at onset. GBS variants include²¹:

• Acute motor axonal neuropathy (AMAN)^1,22

• Acute inflammatory demyelinating polyneuropathy (AIDP)¹

• Pharyngeal-cervical-brachial variant²³

• Purely sensory variant24

• Miller-Fisher syndrome, which manifests with ophthalmoplegia, in addition to ataxia and areflexia²⁵

• Axonal form.^5,21

AMAN and AIDP are the most common subtypes of GBS.¹

Symptoms, Signs, and Disease Manifestations
Limb weakness, the classic presenting symptom of GBS, is both symmetrical and ascending. Weakness can develop acutely and progress over days to weeks.^2,15 Hughes and Cornblath²⁶ also note pain, numbness, and paresthesias among the initial symptoms of GBS. Others include sensory changes, cranial nerve involvement, various autonomic changes, and respiratory or oropharyngeal weakness. Reflexes, particularly the tendon reflexes, may be diminished or absent.^15,18,21 In many cases, sensory changes (ie, pain) may precede the onset of weakness, often making diagnosis difficult.¹⁵

Cranial nerves most commonly affected are V, VI, VII, X, XI, and XII, with manifestations that include dysphagia, dysarthria, diplopia, limitation to eye movements, and facial droop and weakness. Usually facial and oropharyngeal weakness occur after the extremities and trunk are affected. Blindness may occur if demyelination of the optic nerve occurs; this is seen in Miller-Fisher syndrome.^10,15,25,27

In GBS, many patients report pain, which can present as bilateral sciatica or as throbbing or aching in the large muscles of the upper legs, flanks, or back.28 This pain, which results from the demyelination of the sensory nerve fibers, can be severe.10

Patients with GBS may experience manifestations of autonomic nervous system dysfunction—for example, arrhythmias, hypotension or hypertension, urinary retention, cardiomyopathy, and paralytic ileus.^10,20 Dysautonomia often impedes patients’ progress in inpatient rehabilitation. Patients may have persistent problems involving postural hypotension, hypertension, excessive sympathetic outflow, or bladder and bowel dysfunction.²⁹

Blood pressure fluctuations, often attributed to changes in catecholamine levels and disturbances in the baroreceptor reflex pathway, are common and are considered characteristic of GBS. Transient or persistent hypotension is caused by the dysregulation of the parasympathetic and sympathetic systems, with subsequent alterations in venomotor tone.³ Additionally, an increased sensitivity to catecholamine can lead to cardiovascular disturbances, resulting in denervation hypersensitivity and impairment of the carotid sinus reflex.

Arrhythmias occur in perhaps half of patients with GBS. The most common is sustained sinus tachycardia, which usually requires no treatment. Bradycardia leading to atrioventricular blocks and asystole is believed to result from afferent baroreceptor reflex failure. Treatment may be required—either administration of atropine or insertion of a pacemaker, depending on the severity of the arrhythmia.^3,10

Myocardial involvement can range from asymptomatic mycocarditis to neurogenic stunned myocardium and heart failure. Patients with ECG abnormalities should undergo two-dimensional echocardiographic studies and other testing to explore cardiac involvement. Acute coronary syndromes, including ST-segment elevation MI, have been reported, in some cases associated with IVIG treatment. In one patient, coronary spasm was reported, with clean coronary arteries found on cardiac catheterization.³

Patients with GBS are at risk for compromised neuromuscular respiratory function; demyelination of the nerves that innervate the intercostal muscles and the diaphragm can result in respiratory failure. Key clinical indicators of respiratory muscle fatigue include tachypnea, diaphoresis, and asynchronous movements of the abdomen and chest;¹⁰ other symptoms relevant to respiratory or oropharyngeal weakness include slurred speech, dyspnea (with or without exertion), difficulty swallowing, and inability to cough.^2,10 Serial respiratory function testing is advisable to detect patients at risk for respiratory failure.³⁰