Guillain-Barre syndrome--a review.

Guillain-Barre syndrome, also known as acute inflammatory demyelinating polyneuropathy, acute idiopathic polyneuritis, and Landry's ascending paralysis, is a rare neuromuscular disorder characterized by an acute, ascending neuropathy. The progressive muscle weakness that accompanies this disease results from the involvement of the motor neurons of the peripheral nervous system. However, spinal and cranial nerves, as well as sensory neurons, are often involved. Severe cases can cause paralysis and ventilatory muscle involvement, and ultimately respiratory failure.

NERVOUS SYSTEM REVIEW

The nervous system is divided into two divisions based on the location of each. These divisions are the central nervous system and the peripheral nervous system. The central nervous system consists of the brain and spinal cord, which are centrally located. The peripheral nervous system is comprised of the cranial nerves, spinal nerves, autonomic nerves, and ganglia.

The peripheral nervous system contains afferent and efferent neurons. The afferent neurons are sensory nerves that conduct impulses toward the central nervous system from receptors located throughout the body. The efferent neurons are motor neurons that conduct impulses away from the central nervous system.

The nervous system is further divided into the somatic nervous system and the autonomic nervous system. The somatic nervous system innervates skeletal, or voluntary, muscles, and entails the brain, spinal cord, cranial nerves, and spinal nerves. The autonomic nervous system innervates involuntary muscles such as smooth muscles of various internal organs, cardiac muscle, and exocrine and endocrine glands.

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The autonomic nervous system itself has two subdivisions called the sympathetic nervous system and the parasympathetic nervous system.

EPIDEMIOLOGY

The incidence of occurrence of Guillain-Barre is approximately 1 in 1,000, making this neuromuscular disease a somewhat uncommon affliction. People of all ages are equally susceptible although males tend to contract this condition more frequently than females by a ratio of 1.5:1.0.

ETIOLOGY

The cause of Guillain-Barre syndrome is unknown. Nonetheless, around 50% of the incidence of this disorder closely follows either a viral or bacterial infection. Infections linked to this condition include viral hepatitis, flu (common cold), Campylobacter jejuni infection (generally from consuming undercooked poultry), and infectious mononucleosis. Some cases of Guillain-Barre develop after surgery. This etiologic factor accounts for approximately 5% of Guillain-Barre cases.

Research, however, links the cause of Guillain-Barre to an autoimmune deficiency, whereby the body produces antibodies against itself. In this disorder the antibodies destroy the myelin sheath that surrounds the peripheral motor neurons and cause inflammation of the axons of the affected nerve cells.

Despite the fact that some people contract Guillain-Barre after obtaining a vaccination, a strong correlation has not surfaced since 1976 and 1977 when many cases of Guillain-Barre developed among a large segment of the population inoculated with the Swine flu vaccine.

CLINICAL MANIFESTATIONS

Initially patients with Guillain-Barre will often experience tingling or numbness in their fingers and toes. This classic symptom, called paresthesia, is described as being symmetrical, that is, affecting both sides of the body. A loss of reflexes, described as areflexia, is also a common symptom.

Pain is often described as occurring in the lower back and buttocks, and may be felt in the legs, thighs, and shoulders.

Muscle weakness tends to follow the sensation of peripheral tingling and numbness, and often ascends to other areas of the body, including the thorax. In severe cases, paralysis of the respiratory muscles ensues and produces a life-threatening situation, requiring endotracheal intubation and mechanical ventilation. Not all patients with Guillain-Barre progress to the severe stage. Approximately, only 25% do. The others experience a lesser degree of debility.

The majority of patients have cranial nerve involvement. Consequently, most Guillain-Barre patients experience dysphagia, dysphasia, dysarthria (poorly articulated speech), or facial weakness. Unlike the symmetrical nature of peripheral motor neuron involvement, cranial nerve involvement is asymmetrical.

Autonomic nervous system dysfunction includes hyperhidrosis, postural hypertension, blood pressure fluctuation, tachycardia, and urinary retention. Once the condition becomes symptomatic, progression of the disease often continues for hours, days, or two weeks. The condition usually peaks within two weeks after the appearance of the initial symptoms.

PATHOPHYSIOLOGY

The myelin sheath that circumscribes the peripheral motor neurons is destroyed. This pathophysiologic alteration causes a delay in the conduction time of the impulses transmitted along the peripheral motor neuron pathways. The efferent (motor) neurons no longer are able to conduct nerve impulses along their pathways efficiently. Consequently, muscle contraction is either weak or absent.

At the same time, fewer afferent (sensory) signals reach the central nervous system. The result is an inability to sense heat, pain, textures, and other sensations. In fact, the central nervous system may receive inappropriate impulses, which produce tingling of the periphery, sensation of pain, and the complaint of "crawling skin."

From an immunologic perspective, the immune system goes awry. Cells of the immune system misidentify the myelin sheath surrounding the peripheral motor neurons and destroy it. Essentially, sensitized T-lymphocytes and B-lymphocytes produce antibodies against the myelin sheath.

DIAGNOSIS

Guillain-Barre is characterized by a constellation of signs and symptoms; therefore, it is called a syndrome. Features such as symmetrical presentation of symptoms, peripheral involvement (paresthesia) preceding muscle weakness of the trunk, and the acuity or rapidity of onset, help differentiate this condition from other neuromuscular diseases. The loss of certain reflexes such as the knee-jerk reflex and deep tendon reflexes aids in the diagnosis.

Generally, three different diagnostic studies are performed to help identify the condition as Guillain-Barre. A spinal tap is usually done to examine the cerebrospinal fluid (located in the subarachnoid space bathing the brain and spinal cord) for an abnormally elevated protein concentration. Results may not be conclusive because an elevated level of protein in the cerebrospinal fluid may be immeasurable soon after the patient presents with symptoms. An elevated level of protein in the cerebrospinal fluid tends to show up after about one to two weeks following the onset of symptoms. Protein levels greater than 400 mg/L in this fluid compartment are present in about 90% of Guillain-Barre cases. Caution, however, must be exercised because an increased cerebrospinal fluid protein level occurs in other forms of acute and chronic polyneuritis. Furthermore, 10% of these patients display a normal level.

A nerve conduction velocity test is used to measure how fast nerve impulses travel along neurons. Slow or absent impulses along motor neuron pathways prove valuable in the diagnosis of Guillain-Barre. However, about two to three weeks generally elapse before the slowing of nerve conduction velocity can be perceived.

Along with the nerve conduction velocity test, an electromyogram is performed to determine the status of muscle reflexes. Areflexia frequently accompanies Guillain-Barre and occurs in conjunction with delayed impulse velocity along peripheral pathways.

TREATMENT

Although Guillain-Barre can resolve spontaneously, the patient must be admitted to the ICU once the diagnosis has been made. From that point treatment is primarily focused on supportive care because Guillain-Barre is a potential medical emergency. As with other forms of neuromuscular disease, serial spirometric analyses, oxygen saturations, blood gas analyses, and blood pressure measurements should be performed to monitor the progression of the impending respiratory failure.

Deterioration of the patient's ventilatory status is evidenced by a decreased FVC and a normal FEV1/FVC ratio (restrictive disease pattern), a decreased PaO2 and an increased PaCO2.

In addition to declining pulmonary function values and arterial blood gas abnormalities, other signs of impending respiratory failure include paradoxical breathing and respiratory alternans, caused by diaphragmatic involvement. The onset of respiratory failure is gradual. However, clinicians must be prepared to perform endotracheal intubation and to initiate mechanical ventilation once the trend toward respiratory failure has been identified. Mechanical ventilation generally is required for about two weeks.

In the meantime, bronchial hygiene techniques are part of the therapeutic regimen because neuromuscular disease patients often experience secretion retention, impaired cough mechanism, and compromised swallowing. Oxygen is administered to correct hypoxemia resulting from alveolar hypoventilation.

Other forms of treatment used in cases of Guillain-Barre include plasmapheresis and the IV administration of immunoglobulin. Plasmapheresis is the procedure in which blood is separated into cells and plasma. The plasma is removed and replaced with fresh frozen plasma, albumin, or a plasma substitute. This process is believed to remove the antibodies responsible for the destruction of the myelin sheath. The goal of plasmapheresis is to shorten the course of the disease, to alleviate symptoms, and to prevent paralysis.

The injection of IV immunoglobulin has become the first line of treatment. IV immunoglobulin has numerous modes of action. These actions include 1) binding with and neutralizing autoimmune antibodies, 2) inhibiting the production of autoimmune antibodies, 3) suppressing autoimmune dependent cellular toxicity, 4) decreasing natural killer cell function, 5) down-regulating pro-inflammatory cytokines, and 6) interfering with complement activation. However, both plasmapheresis and IV immunoglobulin therapy are equally effective in the treatment of Guillain-Barre.

PROGNOSIS

The prognosis for patients with Guillain-Barre is excellent, as 85% of the patients make a complete recovery. The mortality rate is less than 5%. The remainder experience long-term debilitation likely from the damage done to the axons of the motor neurons. This damage appears to be related to the severity of the destruction of the myelin sheath.

After about two weeks, symptoms stabilize for a few days, weeks, or months. Recovery may occur in a few weeks or a few years. About 30% of those with Guillain-Barre still have a residual weakness after 3 years. About 3% may suffer a relapse of muscle weakness and tingling sensations many years after the initial attack.

Some patients who have recovered from Guillain-Barre develop the symptoms of post-polio syndrome. Post-polio syndrome is a condition that afflicts people who recovered from polio years ago.

by Bill Wojciechowski, MS, RRT