INCIDENCE

Since the incidence of poliomyelitis has declined markedly due to mass immunisation programmes, GBS has become the major cause of rapid-onset flaccid paralysis in previously healthy people, with an incidence of approximately 1.7 per 100 000. Epidemics have occurred in large populations exposed to viral illness or immunisation.⁴ Immunosuppression and concurrent autoimmune disease may also be predisposing factors.⁵ The disorder is slightly commoner in males, and up to four times commoner in the elderly. No consistent seasonal or racial predilection has been demonstrated.

AETIOLOGY

Most recent evidence supports the proposition that GBS is caused by immunologically mediated nerve injury.⁶ Cell-mediated immunity, in particular, probably plays a significant role, and inflammatory cell infiltrates are often seen in association with demyelination, which is generally regarded as the primary pathologic process. Antibodies to a number of nervous system components have been demonstrated in GBS patients, with most interest in recent years focusing on antiganglioside antibodies.

Although the precise mechanism of sensitisation is not known, clinical associations suggest that antecedent viral infections or immunisations are commonly involved. Infective agents implicated include influenza A, parainfluenza, varicella-zoster, Epstein–Barr, chickenpox, mumps, human immunodeficiency virus (HIV),⁷ measles virus and Mycoplasma. Campylobacter jejuni gastroenteritis now appears to be the most common predisposing infection and may be associated with a more severe clinical course; 26–41% of GBS patients show evidence of recent C. jejuni infection.⁸ Cytomegalovirus infection accounts for a further 10–22% of cases.⁹ Immunisations against viral infections, tuberculosis, tetanus and typhoid have all preceded the development of GBS. Most of these associations are anecdotal and of doubtful aetiological significance, but 65% of patients present within a few weeks of minor respiratory (43%) or gastrointestinal (21%) illness.

PATHOGENESIS⁶

The peripheral nerves of patients who have died of GBS show infiltration of the endoneurium by mononuclear cells in a predominantly perivenular distribution. The inflammatory process may be distributed throughout the length of the nerves, but with more marked focal changes in the nerve roots, spinal nerves and major plexuses. Electron micrographs show macrophages actively stripping myelin from the bodies of Schwann cells and axons. In some cases, wallerian degeneration of axons is also seen, and failure of regeneration in these cases may correspond with a poor clinical outcome.

The underlying immune response is complex and poorly understood, but serum from GBS patients produces myelin damage in vitro when complement is present.¹⁰ Although antibodies to various glycolipids have been demonstrated in GBS, these are generally in low titre and can occasionally be seen in controls. Patients with recent C. jejuni infection have a high incidence of antibodies to the ganglioside GM1.⁸ Antibodies to GD1a and GQ1b gangliosides are associated with the rarer acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN) variants (see below).¹¹ The basis of the effectiveness of plasma exchange and immunoglobulin therapy is likely to be blocking of demyelinating antibodies by several mechanisms.¹²

CLINICAL PRESENTATION

The majority of patients describe a minor illness in the 8 weeks prior to presentation, with a peak incidence 2 weeks beforehand. Approximately half the patients initially experience paraesthesiae, typically beginning in the hands and feet. One-quarter complain of motor weakness, and the remainder have both.¹³ Motor weakness proceeds to flaccid paralysis, which becomes the predominant complaint. Objective loss of power and reduction or loss of tendon reflexes usually commence distally and ascend, but a more haphazard spread may occur. Cranial nerves are involved in 45% of cases, most commonly the facial nerve, followed by the glossopharyngeal and vagus nerves. One-third of patients require ventilatory support.

In the Miller–Fisher syndrome, a variant of GBS,¹⁴ cranial nerve abnormalities predominate, with ataxia, areflexia and ophthalmoplegia as the main features. This is strongly associated with recent C. jejuni infection and with the presence of GQ1b antibodies.

Another subgroup of patients presents with a primarily axonal neuropathy – AMSAN. In these cases motor and sensory axons appear to be the primary targets of immune attack, rather than myelin. These patients have a more fulminant and severe course, and there is again a strong association with C. jejuni infection.

Sensory loss is generally mild, with paraesthesiae or loss of vibration and proprioception, but occasionally sensory loss, pain or hyperaesthesia can be prominent features. Autonomic dysfunction is common, and a major contributor to morbidity and mortality in ventilator-dependent cases.¹⁵ Orthostatic or persistent hypotension, paroxysmal hypertension and bradycardia are all described, as are fatal ventricular tachyarrhythmias. Sinus tachycardia is seen in 30% of cases. Paralytic ileus, urinary retention and abnormalities of sweating are also commonly seen.

DIFFERENTIAL DIAGNOSIS

Most of the important alternative diagnoses are listed as exclusion criteria in Table 49.2. In patients with prolonged illness, the possibility of chronic inflammatory demyelinating polyradiculopathy (CIDP) should be considered.¹⁶ In this condition, which is usually distinguished from GBS, preceding viral infection is uncommon, the onset is more insidious and the course is one of slow worsening or stepwise relapses. Corticosteroids and plasma exchange are possibly effective in this disorder, but adequate studies of immunosuppressive drugs have not been carried out.

Table 49.2 Diagnostic criteria for typical Guillain–Barré syndrome³

An intermediate subacute polyradiculopathy (SIDP) as well as a recurrent form of GBS are also described, and all of these variants may be part of the spectrum of a single condition. However, a purely motor axonal neuropathy (AMAN), which causes seasonal childhood epidemics mimicking classical GBS in China and elsewhere,¹⁷ appears to be a distinct entity. Once again, this is strongly associated with C. jejuni infection.

INVESTIGATIONS

In over 90% of patients, CSF protein is increased (greater than 0.4 g/l), within a week of onset of symptoms. The level does not correlate with the clinical findings. A pleocytosis with lymphocytes and monocytes in the CSF may be seen in a small proportion of patients, especially later in the disease. Nerve conduction studies typically demonstrate reduced conduction velocity and prolonged distal latencies,¹⁸ but there is no consensus on precise electrophysiological criteria for the various subtypes.¹¹ Severely reduced distal motor amplitude and a predominantly axonal pattern are associated with more severe disease and a guarded prognosis.

MANAGEMENT

The management of the patient with severe and protracted GBS provides a major challenge, as the prognosis is generally excellent if complications can be treated early or avoided. These complications may be life-threatening, affect any of the major organ systems or result in permanent disability, and can be prevented only by meticulous attention to detail.

SPECIFIC THERAPY

Plasma exchange (plasmapheresis) is of value in GBS. Two large controlled trials showed a reduction in patients requiring mechanical ventilation, reduced duration of mechanical ventilation for those who required it, reduced time to motor recovery and time to walking without assistance.¹⁹ Mortality, however, was not altered. Plasma exchange was most effective when carried out within 7 days of onset of symptoms. The plasma exchange schedules consisted of three to five exchanges of 1–2 plasma volumes each, over 1–2 weeks. Adverse events are common, and some relate to the disease itself. Fresh frozen plasma is reported to have more side-effects than albumin as the replacement fluid.

Immunoglobulin therapy was as effective as plasmapheresis²⁰ and previous concerns of higher recurrence rates are probably unfounded. Because of its ease of use, many authorities now advocate immunoglobulin as the treatment of choice. A dose of 0.4 g/kg body weight intravenously, daily for 5 days, was used in the most recent trials.

About 10% of patients relapse after initial treatment with either plasmapheresis or immunoglobulin; most respond well to a further course.

A recent Cochrane review confirms that low- or high-dose corticosteroids are of no value,²¹ and may even slow recovery. The combination of high-dose steroids with immunoglobulin may hasten recovery, but does not affect the long-term outcome.

SUPPORTIVE CARE