Guillain-Barré Syndrome

 Guillain-Barré syndrome (GBS) is a polyneuropathy of acute onset with an annual incidence of between 1 and 4 cases per 100,000 population worldwide. Several distinct subtypes of the syndrome have been described, including acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which will be discussed in this chapter. AIDP is the most common subtype of GBS, comprising about 95% of cases in North America and Europe. It is caused by an immune attack directed mainly at peripheral nervous system myelin sheaths, leading to the extensive demyelination that accounts for the ascending paralysis and other clinical manifestations of the disease.

Etiology

About one third of cases are idiopathic, as no obvious trigger is identified. In most cases, infections such as upper respiratory tract infections or especially Campylobacter jejuni precede the condition. Mycoplasma pneumoniae and viruses—including cytomegalovirus and Epstein-Barr virus—have also been implicated as triggers of GBS. Immunizations—including tetanus toxoid, influenza vaccine, and rabies vaccine—have been suspected of causing GBS as well. Clusters of GBS cases have occurred in association with other illnesses and events (such as surgery, childbirth, or immunization), leading to the proposal of causative relationships. Signs and symptoms of GBS typically occur within 6 weeks of the manifestations of the infection, which often include gastroenteritis and flulike symptoms. It is hypothesized that antibodies synthesized in response to certain infections crossreact with myelin sheath or Schwann cell components, resulting in peripheral nerve demyelination.

Clinical Manifestations

GBS should be suspected in patients who complain of acute muscle weakness and other neurologic symptoms, especially after a recent febrile illness. Most cases begin with numbness, paresthesia, and weakness in the distal extremities; rapid proximal progression of ascending paralysis is typical. On physical examination, deep tendon reflexes are absent or hypoactive, and muscle weakness is usually symmetric. Muscle wasting is often delayed, but can be detected in severe cases. Also frequently affected are cranial and autonomic nerves, and dysfunction of the latter can lead to hypertension, cardiac arrhythmia, postural hypotension, urinary retention, and ileus. Inability to protect the airway and facial muscle weakness are frequent manifestations of cranial nerve involvement in patients with GBS.

Severity of disease peaks between 2 and 4 weeks in most patients; respiratory muscle weakness leads to hypoventilation and the need for mechanical ventilation in up to 25% of cases. After a plateau phase of variable length, improvement in proximal muscle strength begins. Over weeks to months, neurological recovery progresses in the opposite direction of the onset of the disease, from proximal to distal.

Diagnosis

The differential diagnosis for a patient with acute flaccid paralysis is extensive. However, data from neurophysiologic electrodiagnostic studies and cerebrospinal fluid (CSF) analysis in the setting of a patient with typical clinical manifestations can help confirm the diagnosis of GBS. Neurophysiologic studies are important not only in diagnosing GBS, but also in differentiating among its subtypes and in the prognosis. In AIDP, the findings on nerve conduction studies demonstrate the demyelination that produces the clinical manifestations. These electrodiagnostic studies can be normal early in the disease, but testing becomes diagnostic in all but the most mild of cases as the disease progresses; thus, they should be repeated serially and expanded to include more nerves if the initial testing is normal.

Lumbar puncture with CSF analysis can also assist with making the diagnosis. There is an elevated CSF protein concentration without associated pleocytosis; this phenomenon is known as albuminocytologic dissociation and is characteristic of GBS. An elevated CSF white blood cell count associated with acute muscle weakness is suggestive of an alternative diagnosis, especially infectious or neoplastic. The timing of the lumbar puncture is important, as the CSF protein level can be normal for the first 48 hours after symptoms begin. Also, the sample should preferably be obtained before treatment is begun, since intravenous immunoglobulin therapy may cause aseptic meningitis with elevated CSF white blood cell count.

Differentiation between GBS and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is based on the timing of the nadir of disease. When the progression of disease extends beyond 4 weeks, patients are likely to have CIDP, as opposed to those who develop a disease severity nadir before 4 weeks consistent with GBS. Patients with CIDP are likely to have a relapsing-remitting or a more chronic course of disease than that of patients with GBS.

Treatment

Both supportive and specific therapies are important in the treatment of GBS. Multidisciplinary supportive measures are essential in detecting and managing the potentially fatal consequences of this disease. Serial vital capacity and negative inspiratory force should be monitored closely with transfer to an intensive care unit for early endotracheal intubation and mechanical ventilation if these parameters worsen, as respiratory failure may occur in about one-quarter of GBS cases. Abnormalities in cardiac rhythm and vital signs are often the first signs of autonomic complications of the disease; thus, it is important to closely monitor this aspect of patient care. Prophylaxis for peptic ulcer and deep venous thrombosis is warranted, as is early detection and management of urinary retention, ileus, and pain. Consultation with physical, occupational, and speech therapy are integral in the management of patients with GBS.

Specific therapies for patients with GBS are directed toward the autoimmune pathogenesis of the disease. Although corticosteroids have been found to be largely ineffective in patients with GBS, plasma exchange and intravenous immunoglobulin (IVIg) have been shown to decrease the percentage of patients who require mechanical ventilation and increase the number of patients who have recovered full strength after 1 year. The ease of administration of IVIg has made this the treatment of choice instead of plasma exchange in many hospitals, given the similar efficacy of the two treatments. Debate on the indication for specific therapies is ongoing, even though IVIg or plasmapheresis is generally recommended in adult patients when ambulation becomes limited. Influenza vaccine is often avoided in patients with a previous history of postvaccination GBS.

Complications

As previously mentioned, respiratory and autonomic failure are the most feared acute complications of GBS, leading to a reported mortality of between 4% and 15%. Persistent weakness is more common, leading to disability in up to 20% of patients after 1 year despite receiving standard treatment. Elderly patients, those who require mechanical ventilation for respiratory failure, and patients who are bedbound from their weakness are more likely to suffer from ongoing disability. Chronic fatigue, even in those patients who have recovered muscle strength clinically, can be a long-term complication of GBS; this is possibly related to persistent subclinical abnormalities that are present on electrodiagnostic testing.