GBS often occurs 2 to 4 weeks after a flulike or diarrheal illness caused by a variety of infectious agents [3], including cytomegalovirus, Epstein–Barr and herpes simplex viruses, mycoplasma, chlamydia, and Campylobacter jejuni [5]. It can also be an early manifestation of human immunodeficiency virus (HIV) infection before the development of an immunosuppressed state [6]. Lyme disease may rarely produce a syndrome of polyradiculopathy reminiscent of GBS [7]. Other antecedent events include immunization, general surgery and renal transplantation, Hodgkin’s disease, and systemic lupus erythematosus [2,3].

The illness is heralded by the presence of dysesthesias of the feet or hands, or both. The major feature is weakness that evolves rapidly (usually over days) and classically has been described as ascending from legs to arms and, in severe cases, to respiratory and bulbar muscles. Weakness may, however, start
in the cranial nerves or arms and descend to the legs or start simultaneously in the arms and legs [2]. Approximately 50% of patients reach the nadir of their clinical course by 2 weeks into the illness, 80% by 3 weeks, and 90% by 1 month [8]. Progression of symptoms beyond 4 weeks but arresting within 8 weeks has been termed subacute inflammatory demyelinating polyneuropathy (SIDP) [9], while progression beyond 2 months is designated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a disorder with a natural history different from GBS [10]. A small percentage of patients (2% to 5%) have recurrent GBS [11].

The extent and distribution of weakness in GBS are variable. Within a few days, a patient may become quadriparetic and respirator dependent, or the illness may take a benign course and after progression for 3 weeks produce only mild weakness of the face and limbs.

In a typical case of moderate severity, the physical examination discloses symmetric weakness in proximal and distal muscle groups associated with attenuation or loss of deep tendon reflexes (Table 175.1). In the early stage of illness, there is no muscle wasting or fasciculation. If the attack is particularly severe and axons are interrupted, then after a number of months, muscles undergo atrophy and scattered fasciculations may be seen (see later). Sensory loss is usually mild, although a variant of GBS is described in which sensory loss (involving large fiber modalities) is widespread, symmetric, and profound [8]. Respiratory muscles are often involved; between 10% and 25% of patients require ventilator assistance [12] initiated within 18 days (mean of 10 days) after onset [13].

There is often mild to moderate bilateral facial weakness. Mild weakness of tongue muscles and the muscles of deglutition may also develop. Ophthalmoparesis from extraocular motor nerve involvement is unusual in the typical patient with GBS. In the Miller–Fisher variant [14], however, there is ophthalmoplegia in combination with ataxia and areflexia, with little limb weakness per se. Pupillary abnormalities have been noted in GBS [15] and in the Miller–Fisher variant [16]. Papilledema is exceedingly rare [17].

Disturbances of the autonomic nervous system are found in 50% of patients and are potentially lethal [3,4]. Autonomic dysfunction takes the form of excessive or inadequate activity of the sympathetic nervous system or the parasympathetic nervous system, or both [18]. Common findings include cardiac arrhythmias (e.g., persistent sinus tachycardia, bradycardia, ventricular tachycardia, atrial flutter, atrial fibrillation, and asystole), orthostatic hypotension, and transient and persistent hypertension. Other changes include transient bladder paralysis, increased or decreased sweating, and paralytic ileus. These changes are not completely understood but may be due to inflammation of the thinly myelinated and unmyelinated axons of the peripheral autonomic nervous system. A neuropathy predominantly affecting the peripheral autonomic nervous system has been described that may have a pathogenesis similar to that of GBS [19].

Axonal forms, like AIDP, present with rapidly progressive weakness, areflexia, and albuminocytological dissociation but differ in the following ways. AMAN patients lack sensory abnormalities and are more commonly found in northern China during summer months among children and young adults. Patients with AMAN also appear to have a more rapid progression to nadir, but recovery times are quicker [20] or similar [21] to AIDP in some patients, while others have a more prolonged course [20].

AMSAN is generally associated with a more severe course and longer time to recovery. In the series by Feasby et al. [22], these patients had a much shorter time to peak severity (1 week), more severe symptoms with more than half requiring mechanical ventilation, inexcitable motor nerves, and most had a poor recovery.

The most characteristic laboratory features of GBS are an abnormal cerebrospinal fluid (CSF) profile showing albuminocytologic dissociation (elevated protein without pleocytosis) and abnormal nerve conduction studies.

CSF examination is most helpful in reaching the diagnosis of GBS. Although the CSF profile is usually normal during the first 48 hours after onset [8], by 1 week into the illness, the CSF protein is elevated in most patients, sometimes to levels as high as 1 g per dL. Rarely, even several weeks after onset of GBS, the CSF protein remains normal and the diagnosis must rest on the presence of otherwise typical clinical features [8]. The cell count may be slightly increased but rarely exceeds 10 cells per μL; the cells are mononuclear in nature. When GBS occurs as a manifestation of HIV infection or Lyme disease, the CSF white cell count is generally increased (25 to 50 cells per μL. The CSF glucose is expected to be normal.

Electrodiagnostic studies in AIDP typically disclose slowing (less than 80% of normal) of nerve conduction velocity, most often along proximal nerve segments, with increases in distal motor and sensory latencies [8,23]. The amplitude of the evoked motor responses may be reduced because of axon loss or distal nerve conduction block, and the responses are frequently dispersed because of differential slowing along still-conducting axons [8,23]. Because the pathologic process may be restricted to spinal nerve roots and proximal nerve segments, routine nerve conduction studies may be normal on initial testing. In such cases, however, H-reflexes may be absent and F-responses may be abnormal because of involvement of the most proximal segments of the motor fibers. This, together with a normal sural nerve and abnormal upper extremity sensory action potential, is characteristic of early GBS [24].
Also early in the course of GBS, needle electrode examination electromyography may demonstrate only decreased numbers of motor unit potentials firing on voluntary effort because of nerve conduction block. Several weeks later, active denervation changes, such as fibrillation potentials and positive sharp waves, may be seen if axon loss has occurred.

In patients with the severe axonal form of GBS, AMSAN, motor and sensory nerves may be electrically inexcitable [22]. In AMAN, motor responses are low or absent while conduction velocities and sensory responses are normal [25].

Except for a mild increase in the erythrocyte sedimentation rate, hematologic studies are normal. Serum electrolytes may disclose hyponatremia [3], sometimes to a marked degree, because of inappropriate secretion of antidiuretic hormone caused by a disturbance of peripheral volume receptors. There may be evidence of previous viral or mycoplasma infection, such as lymphopenia or atypical lymphocytes. In some cases, evidence of recent viral infection may be sought by measuring antibody (immunoglobulin [Ig] M) titers against specific infectious agents, especially cytomegalovirus, Epstein–Barr virus, and C. jejuni. In selected cases, screening for HIV infection should be undertaken.

Unlike neuromuscular emergencies such as GBS, myasthenia gravis, or porphyria, in which rapidly progressive weakness develops before admission to the ICU, a number of conditions (polyneuropathy, myopathy, and neuromuscular junction disease) affect patients already in the ICU because of severe systemic illnesses. These conditions are discussed in more detail in Chapter 180. Critical illness polyneuropathy is an axonal sensory-motor polyneuropathy characterized by difficulty weaning from the ventilator, distal greater than proximal muscle weakness, and reduced or absent reflexes that develop in patients with sepsis and multiorgan failure [26]. The development of weakness in the midst of critical illness, as seen in critical illness polyneuropathy, helps differentiate this disorder from axonal GBS, in which weakness develops days to weeks after an infection [27]. A severe necrotizing myopathy can also be seen in critically ill patients [28]. An acute myopathy of intensive care initially described in patients treated with a combination of high-dose corticosteroids (equal to or greater than 1,000 mg methylprednisolone) and neuromuscular blocking agents (NMBAs) for status asthmaticus [29] may also be encountered in the setting of trauma, organ transplantation, burns, and critical illness. Patients have variable degrees of generalized weakness, including respiratory muscles, and this is often recognized when a patient has difficulty weaning from the ventilator. Prolonged neuromuscular blockade after use of the nondepolarizing NMBAs can be seen especially in patients with coexistent renal failure and metabolic acidosis. Presumably, the presence of an active metabolite accounts for the prolonged weakness [30].

In patients with myasthenia gravis, limb weakness is predominant proximally and almost always associated with ocular and sometimes pharyngeal muscle weakness (see Table 175.2; see Chapter 176). Muscular fatigability is a hallmark of the disease. Botulism may also cause acute weakness 6 to 36 hours after ingestion of the toxin formed by Clostridium botulinum. The condition is characterized by weakness of cranial nerve–innervated muscles, autonomic abnormalities (unreactive pupils and ileus), and occasional respiratory muscle weakness necessitating ventilator assistance.