Guillain-Barre syndrome

Guillain-Barré syndrome (GBS) is an acute, autoimmune, polyradiculoneuropathy affecting the peripheral nervous system; it is usually triggered by an acute infection. There are several types of GBS, but the most common form is acute inflammatory demyelinating polyneuropathy (AIDP). It is often severe, and usually exhibits as an ascending paralysis noted by weakness in the legs that spreads to the upper limbs and the face with complete loss of deep tendon reflexes. With prompt treatment with immunoglobulins and supportive care, most patients will regain full functional capacity. However, death may occur if severe pulmonary complications and dysautonomia are present.

It is related to chronic inflammatory neuropathies such as Charcot-Marie-Tooth disease.

Pathophysiology

All forms of Guillain-Barre syndrome are due to an immune response to foreign antigens (such as infectious agents or vaccines) that becomes mistargeted to host nerve tissues (a form of antigenic mimickry). The targets of such immune attack are thought to be gangliosides, which are complex glycosphingolipids present in large quantities on human nerve tissues, especially in the nodes of Ranvier. An example is the GM1 ganglioside, which can be affected in 20-50% of cases, especially in those preceded by Campylobacter jejuni infections. Another example is the GQ1b ganglioside, which is the target in the Miller-Fisher syndrome variant (see below).

The result of such autoimmune attack on the peripheral nerves is inflammation of myelin and subsequent conduction block, leading to a rapidly evolving flaccid paralysis which is sometimes accompanied by sensory or autonomic disturbances. However, in mild cases, axonal function remains intact and recovery can be rapid if remyelination occurs. In severe cases, such as in the AMAN or AMSAN variants (see below), axonal degeneration occurs, and recovery depends on axonal regeneration. Recovery is much slower, and there is more residual damage. Recent studies have shown that about 80% of patients have myelin loss, and the remainder have axon loss.

Signs and symptoms

The disease is characterized by weakness which first affects the lower limbs, and rapidly ascends. Patients generally notice weakness in their legs, manifesting as "rubbery legs" or legs that tend to buckle, with or without dysthesias (numbness or tingling). As the weakness progresses upward, usually over hours to days, the arms and facial muscles become affected. Often, the lower cranial nerves are affected, leading to bulbar weakness (causing difficulty with eye movements, double vision), oropharyngeal dysphagia (difficulty with swallowing, drooling, and/or maintaining an open airway). Most patients require hospitalization and about 30% require ventilatory assistance.

Sensory loss, if present, usually takes the form of loss of proprioception (position sense) and areflexia (complete loss of deep tendon reflexes), an important feature of GBS. Loss of pain and temperature sensation is usually mild. In fact, pain is a common symptom in GBS, presenting as deep aching pain usually in the weakened muscles, which patients compare to the pain from overexercising. These pains are self-limited and should be treated with standard analgesics. Bladder dysfunction may occur in severe cases but should be transient. If severe, spinal cord disease should be suspected.

Fever should not be present, and if it is, another cause should be suspected.

In severe cases of GBS, loss of autonomic function is common, manifesting as wide fluctuations in blood pressure, orthostatic hypotension, and cardiac arrhythmias.

Clinical variants

Although ascending paralysis is the most common form of spread in GBS, other variants exist.

• Miller-Fisher Syndrome (MFS) is a rare variant and manifests as a descending paralysis, proceeding in the reverse order of the more common form of GBS. It usually affects the ocular muscles first and presents as ophthalmoplegia, ataxia, and areflexia. Anti-GQ1b antibodies are present in 90% of cases.
• Acute motor axonal neuropathy (AMAN) attacks motor nodes of Ranvier and is prevalent in China and Mexico. The disease may be seasonal and recovery is rapid. Anti-GD1a antibodies are present.
• Acute motor sensory axonal neuropathy (AMSAN) is similar to AMAN but also affects sensory nerves with severe axonal damage. Recovery is slow and often incomplete.

Diagnosis

The diagnosis of GBS usually depends on the typical clinical findings such as rapidly evolving flaccid paralysis, areflexia, absence of fever, and a likely inciting event. CSF and electrodiagnostics may be useful, but because of the acute nature of the disease, they may not become abnormal until the end of the first week.

• CSF - typical CSF findings include an elevated protein level (100 - 1000 mg/dL) without an accompanying pleocytosis (increased cell count). A sustained pleocytosis may indicate an alternative diagnosis such as infection.
• Electrodiagnostics - electromyography (EMG) and nerve conduction study may show prolonged distal latencies, conduction slowing, conduction block, and temporal dispersion of compound action potential in demyelinating cases. In primary axonal damage, the findings include reduced amplitude of the action potentials without conduction slowing.

Diagnostic criteria

• Required
  • Progressive weakness of 2 or more limbs due to neuropathy
  • Areflexia
  • Disease course < 4 weeks
  • Exclusion of other causes (see below)
• Supportive
  • relatively symmetric weakness
  • mild sensory involvement
  • facial nerve or other cranial nerve involvement
  • absence of fever
  • typical CSF findings
  • electrophysiologic evidence of demyelination

Differential diagnosis

• acute myelopathies with chronic back pain and sphincter dysfunction
• botulism with early loss of pupillary reactivity
• diphtheria with early oropharyngeal dysfunction
• Lyme disease polyradiculitis and other tick-borne paralyses
• porphyria with abdominal pain, seizures, psychosis
• vasculitis neuropathy
• poliomyelitis with fever and meningeal signs
• CMV polyradiculitis in immunocompromised patients
• critical illness neuropathy
• myasthenia gravis
• poisonings with organophosphate, poison hemlock, thallium, or arsenic

Treatment

Supportive care with monitoring of all vital functions is the cornerstone of successful management in the acute patient. Of greatest concern is respiratory failure due to paralysis of the diaphragm. Early intubation should be considered in any patient with a vital capacity (VC) <20 ml/kg, a Negative Inspiratory Force (NIF) <-25 cmH₂O, more than 30% decrease in either VC or NIF within 24 hours, rapid progression of disease, or autonomic instability.

Once the patient is stabilized, treatment of the underlying condition should be initated as soon as possible. Either high-dose intravenous immunoglobulins (IVIg) or plasmapheresis can be administered, as they are equally effective and a combination of the two is not significantly better than either alone. Therapy is no longer effective after 2 weeks after the first motor symptoms appear, so treatment should be instituted as soon as possible. IVIg is usually used first because of its ease of administration and safety profile, with a total of five daily infusions for a total dose of 2 g/kg body weight. The use of intravenous immunoglobulins is not without risk, occasionally causing hepatitis, or in rare cases, renal failure if used for longer than five days. Glucocorticoids have NOT been found to be effective in GBS. If plasmapheresis is chosen, a dose of 40-50 mL/kg plasma exchange is administered four times over a week.

Following the acute phase, the patient may also need rehabilitation to regain lost functions. This treatment will focus on improving ADL (activities of daily living) functions such as brushing teeth, washing and getting dressed. Depending on the local structuring on health care, there will be established a team of different therapists and nurses according to the patients needs. An occupational therapist can offer equipment (such as wheel chair and cutlery) to help the patient achieve ADL independence. A physiotherapist would plan a progressive training programme, and guide the patient to correct, functional movement, avoiding harmful compensations which might have a negative effect in the long run. There would also be a doctor, nurse and perhaps a speech trainer involved, depending on the needs of the patient. This team contribute with their knowledge to guide the patient towards his goal, and it is important that all goals set by the team members are relevant for the patient's own priorities. After rehabilitation the patient should be able to function in his own home and attend necessary training as needed.

Prognosis

About 80% of patients recover completely within a few months to a year, although minor symptoms may persist, such as areflexia. About 5-10% recover with severe disability, with most of such cases involving severe proximal motor and sensory axonal damage with inability of axonal regeneration. However, this is a grave disease and despite all improvements in treatment and supportive care, the death rate among patients with this disease is still about 2-3% even in the best intensive care units. Worldwide, the death rate is slightly higher (4%), mostly from a lack of availability of life support equipment during the lengthy plateau lasting 4 to 6 weeks, and in some cases up to 1 year, when a ventilator is needed in the worse cases. About 5-10% of patients have one or more late relapses, in which case they are then classified as having chronic inflammatory demyelinating polyneuropathy (CIDP).

History

The disease was first described by the French physician Jean Landry in 1859. In 1916, Georges Guillain, Jean Alexandre Barré and Andre Strohl discovered the key diagnostic abnormality of increased spinal fluid protein production, but normal cell count.

A study published in 2003, concluded that Franklin Delano Roosevelt's paralytic illness was probably Guillain-Barré syndrome, not polio as previously assumed. The Bayesian analysis in the study found that six of eight posterior probabilities favored a diagnosis of Guillain-Barré syndrome over poliomyelitis.

Joseph Heller, author of Catch-22, suffered from Guillain-Barre syndromé. His experiences make up a large part of his non-fiction book No Laughing Matter.

GBS is also known as acute inflammatory demyelinating polyneuropathy, acute idiopathic polyradiculoneuritis, acute idiopathic polyneuritis, French Polio and Landry's ascending paralysis.