The Condition

What is Guillain-Barre syndrome?
Guillain-Barré (ghee-yan bah-ray) syndrome is a disorder in which the body’s immune system attacks part of the peripheral nervous system. The first symptoms of this disorder include varying degrees of weakness or tingling sensations in the legs. In many instances the weakness and abnormal sensations spread to the arms and upper body. These symptoms can increase in intensity until certain muscles cannot be used at all and, when severe, the patient is almost totally paralyzed. In these cases the disorder is life threatening – potentially interfering with breathing and, at times, with blood pressure or heart rate – and is considered a medical emergency. Such a patient is often put on a respirator to assist with breathing and is watched closely for problems such as an abnormal heart beat, infections, blood clots, and high or low blood pressure. Most patients, however, recover from even the most severe cases of Guillain-Barré syndrome, although some continue to have a certain degree of weakness.

Guillain-Barré syndrome can affect anybody. It can strike at any age and both sexes are equally prone to the disorder. The syndrome is rare, however, afflicting only about one person in 100,000. Usually Guillain-Barré occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal viral infection. Occasionally surgery or vaccinations will trigger the syndrome.
After the first clinical manifestations of the disease, the symptoms can progress over the course of hours, days, or weeks. Most people reach the stage of greatest weakness within the first 2 weeks after symptoms appear, and by the third week of the illness 90 percent of all patients are at their weakest.

What causes Guillain-Barré syndrome?
No one yet knows why Guillain-Barré—which is not contagious—strikes some people and not others. Nor does anyone know exactly what sets the disease in motion.

What scientists do know is that the body’s immune system begins to attack the body itself, causing what is known as an autoimmune disease. Usually the cells of the immune system attack only foreign material and invading organisms. In Guillain-Barré syndrome, however, the immune system starts to destroy the myolin sheath that surrounds the axons of many peripheral nerves, or even the axons themselves (axons are long, thin extensions of the nerve cells; they carry nerve signals). The myolin sheath surrounding the axon speeds up the transmission of nerve signals and allows the transmission of signals over long distances.

In diseases in which the peripheral nerves’ myolin sheaths are injured or degraded, the nerves cannot transmit signals efficiently. That is why the muscles begin to lose their ability to respond to the brain’s commands, commands that must be carried through the nerve network. The brain also receives fewer sensory signals from the rest of the body, resulting in an inability to feel textures, heat, pain, and other sensations. Alternately, the brain may receive inappropriate signals that result in tingling, “crawling-skin,” or painful sensations. Because the signals to and from the arms and legs must travel the longest distances they are most vulnerable to interruption. Therefore, muscle weakness and tingling sensations usually first appear in the hands and feet and progress upwards.

When Guillain-Barré is preceded by a viral or bacterial infection, it is possible that the virus has changed the nature of cells in the nervous system so that the immune system treats them as foreign cells. It is also possible that the virus makes the immune system itself less discriminating about what cells it recognizes as its own, allowing some of the immune cells, such as certain kinds of lymphocytes and macrophages, to attack the myolin. Sensitized T lymphocytes cooperate with B lymphocytes to produce antibodies against components of the myolin sheath and may contribute to destruction of the myolin. Scientists are investigating these and other possibilities to find why the immune system goes awry in Guillain-Barré syndrome and other autoimmune diseases. The cause and course of Guillain-Barré syndrome is an active area of neurological investigation, incorporating the cooperative efforts of neurological scientists, immunologists, and virologists.

How is Guillain-Barré syndrome diagnosed?
Guillain-Barré is called a syndrome rather than a disease because it is not clear that a specific disease-causing agent is involved. A syndrome is a medical condition characterized by a collection of symptoms (what the patient feels) and signs (what a doctor can observe or measure). The signs and symptoms of the syndrome can be quite varied, so doctors may, on rare occasions, find it difficult to diagnose Guillain-Barré in its earliest stages.

Several disorders have symptoms similar to those found in Guillain-Barré, so doctors examine and question patients carefully before making a diagnosis. Collectively, the signs and symptoms form a certain pattern that helps doctors differentiate Guillain-Barré from other disorders. For example, physicians will note whether the symptoms appear on both sides of the body (most common in Guillain-Barré) and the quickness with which the symptoms appear (in other disorders, muscle weakness may progress over months rather than days or weeks). In Guillain-Barré, reflexes such as knee jerks are usually lost. Because the signals travelling along the nerve are slower, a nerve conduction velocity (NCV) test can give a doctor clues to aid the diagnosis. In Guillain-Barré patients, the cerebrospinal fluid that bathes the spinal cord and brain contains more protein than usual. Therefore a physician may decide to perform a spinal tap, a procedure in which the doctor inserts a needle into the patient’s lower back to draw cerebrospinal fluid from the spinal column.

How is Guillain-Barré treated?
There is no known cure for Guillain-Barré syndrome. However, there are therapies that lessen the severity of the illness and accelerate the recovery in most patients. There are also a number of ways to treat the complications of the disease.
Currently, plasma exchange (sometimes called plasmapheresis) and high-dose immunoglobulin therapy are used. Both of them are equally effective, but immunoglobulin is easier to administer. Plasma exchange is a method by which whole blood is removed from the body and processed so that the red and white blood cells are separated from the plasma, or liquid portion of the blood. The blood cells are then returned to the patient without the plasma, which the body quickly replaces. Scientists still don’t know exactly why plasma exchange works, but the technique seems to reduce the severity and duration of the Guillain-Barré episode. This may be because the plasma portion of the blood contains elements of the immune system that may be toxic to the myolin.

In high-dose immunoglobulin therapy, doctors give intravenous injections of the proteins that, in small quantities, the immune system uses naturally to attack invading organisms. Investigators have found that giving high doses of these immunoglobulins, derived from a pool of thousands of normal donors, to Guillain-Barré patients can lessen the immune attack on the nervous system. Investigators don’t know why or how this works, although several hypotheses have been proposed.

The use of steroid hormones has also been tried as a way to reduce the severity of Guillain-Barré, but controlled clinical trials have demonstrated that this treatment not only isn’t effective but may even have a deleterious effect on the disease.

The most critical part of the treatment for this syndrome consists of keeping the patient’s body functioning during recovery of the nervous system. This can sometimes require placing the patient on a respirator, a heart monitor, or other machines that assist body function. The need for this sophisticated machinery is one reason why Guillain-Barré syndrome patients are usually treated in hospitals, often in an intensive care ward. In the hospital, doctors can also look for and treat the many problems that can afflict any paralyzed patient – complications such as pneumonia or bed sores.

Often, even before recovery begins, care givers may be instructed to manually move the patient’s limbs to help keep the muscles flexible and strong. Later, as the patient begins to recover limb control, physical therapy begins. Carefully planned clinical trials of new and experimental therapies are the key to improving the treatment of patients with Guillain-Barré syndrome. Such clinical trials begin with the research of basic and clinical scientists who, working with clinicians, identify new approaches to treating patients with the disease.

What is the long-term outlook for those with Guillain-Barré syndrome?
Guillain-Barré syndrome can be a devastating disorder because of its sudden and unexpected onset. In addition, recovery is not necessarily quick. As noted above, patients usually reach the point of greatest weakness or paralysis days or weeks after the first symptoms occur. Symptoms then stabilize at this level for a period of days, weeks, or, sometimes, months. The recovery period may be as little as a few weeks or as long as a few years. About 30 percent of those with Guillain-Barré still have a residual weakness after 3 years. About 3 percent may suffer a relapse of muscle weakness and tingling sensations many years after the initial attack.

Guillain-Barré syndrom patients face not only physical difficulties, but emotionally painful periods as well. It is often extremely difficult for patients to adjust to sudden paralysis and dependence on others for help with routine daily activities. Patients sometimes need psychological counselling to help them adapt.

What research is being done?
Scientists are concentrating on finding new treatments and refining existing ones. Scientists are also looking at the workings of the immune system to find which cells are responsible for beginning and carrying out the attack on the nervous system. The fact that so many cases of Guillain-Barré begin after a viral or bacterial infection suggests that certain characteristics of some viruses and bacteria may activate the immune system inappropriately. Investigators are searching for those characteristics. Certain proteins or peptides in viruses and bacteria may be the same as those found in myolin, and the generation of antibodies to neutralize the invading viruses or bacteria could trigger the attack on the myolin sheath. As noted previously, neurological scientists, immunologists, virologists, and pharmacologists are all working collaboratively to learn how to prevent this disorder and to make better therapies available when it strikes.

Where can I get more information?
For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute’s Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

GBS/CIDP Foundation International
The Holly Building
104 1/2 Forrest Avenue
Narberth, PA 19072
email
http://www.gbs-cidp.org
Tel: 610-667-0131
Fax: 610-667-7036

Guillain-Barré syndrome is an acute, inflammatory, postinfectious polyneuropathy marked by a prodromal malaise with nausea, vomiting, headache, fever (may or may not be present) and joint pain. GBS is rapidly surmounted by a progressive and ascending paralysis which can lead to respiratory dysfunction. The acute presentation is a neurological emergency.

GBS is a form of autoimmune disease with a delayed hypersensitivity reaction. It is a rare manifestation of serum sickness or a transient syndrome resembling serum sickness with hematuria, loss of appetite, nausea, vomiting, and stomach pain accompanied by weakness (tired feeling), chills, low grade fever and possible evidence of brain involvement, indicated by lethargy and migraine headaches which may initially suggest a course of viral hepatitis, although one theory of the cause of migraine is a central nervous system (CNS) disorder. Serum sickness is of itself a type of delayed allergic response. Vaccines, broad spectrum antibiotics and “virus in stealth” to help kill cancer cells are themselves an onslaught on the immune system which can cause serum sickness leading to GBS or “provocation polio”, which is a hallmark of GBS. The most serious complications of serum sickness are nerve conditions such as Guillain-Barre syndrome and peripheral neuritis.

T cells, which are mediators of immune function are also involved in the pathogenesis of most or perhaps all forms of GBS. The flaccid phase may be overthrown by the inadvertent generation of mutant T cell receptors that are anti-self; i.e., a super-immune response sending white blood cells (called T cells) rampaging through the body destroying its own tissues. We have an overactive immune system followed by an exhausted immune system. Unpleasant signs or symptoms, such as high blood pressure, headaches, backaches, and upset stomach, will take control, steering the body and the exhausted immune system into dangerous waters, ie. Sarcoidosis is caused by an overactive immune system allowing inflammation to spread out of control. Nutrient deficiency may also contribute to a depressed immune system and may ALSO be observed in patients with GBS. T cells belong to a group of white blood cells known as lymphocytes. T cell depression in serum sickness, marked by a drop in the absolute number of lymphocytes (T-cells literally become worn out) is usually associated with iatrogenic causes, most often secondary to drugs, notably penicillin based medicines and sulfonamides such as Bactrim. It is also well documented that Cipro causes drug-induced serum sickness which can rapidly progress to GBS. Guillain-Barré syndrome and clinically similar states have been reported to occur with a variety of drugs and biologics, including radiation therapy. Many of the cases seem to be triggered by a microbial infection actually follow its course with a causal link to the drugs and the treatment. Catastrophic over-stimulation of the immune system in patients with or without serum sickness can trigger GBS. Alteration in the permeability of the blood-brain barrier may predispose.

Guillain-Barré syndrome (GBS) has become an umbrella term for different disorders representing a collection of clinical syndromes, some of which may overlap each other. All forms of Guillain-Barré syndrome are due to an immune response to foreign antigens (such as infectious agents or vaccines) but mistargeted to host nerve tissues instead (a form of antigenic mimicry). 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 as many as 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, a syndrome of ophthalmoplegia, ataxia and areflexia associated with acute idiopathic ophthalmologic neuropathy. Strictly speaking, that and only that, is MFS. The connection with GBS comes because some GBS patients have paralysed eye muscles too. Consequently, MFS and GBS can overlap. Miller Fisher-Guillain-Barre overlap syndrome is a postinfectious allergic reaction involving both peripheral nerves in the cranium and neuraxis in the spinocerebellar tract. Lesions in the spinocerebellar tracts may be responsible for cerebellar ataxia in this syndrome (see below).

The end result of such autoimmune attack on the peripheral nerves is inflammation of myolin and subsequent conduction block, leading to a rapidly evolving flaccid paralysis with or without accompanying sensory or autonomic disturbances. Autonomic neuropathy is a group of symptoms caused by damage to nerves that regulate blood pressure, heart rate, bowel and bladder emptying, digestion, and other body functions. Constipation is often a problem, due to the reduced activity of the intestines, change of diet, weakened stomach muscles that resist efforts by the patient to express the intestinal content. Bowel and bladder dysfunction with intestinal muscle paralysis; constipation, obstipation and megacolon is a consequence of defect in the nerve supply of the colon. Urinary retention and paralytic ileus may also be observed. Paralysis results because the immune system destroys the insulation that covers nerves. Nerve signals can’t pass to muscles. Physical findings include delayed pupillary light response, resting tachycardia, sinus arrhythmia, and orthostatic hypotension.

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 becomes much slower, and there is a greater degree of residual damage. Recent studies on the disease have demonstrated that approximately 80% of the patients have myolin loss, whereas, in the remaining 20%, the pathologic hallmark of the disease is indeed axon loss.

CNS pathology is frequent in patients with Guillain-Barré syndrome. It involves axons with secondary myolin impairment, microglial activation and inflammatory infiltration. Changes such as degeneration of spinal posterior tracts are secondary to pathology in the peripheral nervous system (PNS). The PNS nerves connect the central nervous system (CNS), which consists of the brain and spinal cord and their associated supportive tissue, to the rest of the body. Guillain-Barré syndrome is a rare disorder that causes the immune system to attack the peripheral nervous system (PNS). Inflammatory cell reactions in the CNS are similar to those in the PNS and to CNS pathology in allergic neuritis. In the month or so before the syndrome’s appearance, patients most often have had a respiratory or digestive-tract infection.

Signs and symptoms
The symptoms of GBS vary a great deal from patient to patient, and so each can have a unique case history. The severity of symptoms can vary considerably between individuals. Symptoms can range from mild muscle weakness that resolves quickly, to complete muscle paralysis. Symptoms of Guillain-Barre get worse very quickly. It may take only a few hours to reach the most severe symptoms.

Guillain-Barre Syndrome frequently follows an antecedent flu-like illness within two weeks prior to the onset of neurological symptoms occurring in approximately 65% of cases. Fast onset of fatigue is a common symptom in patients with Guillain-Barré Syndrome and can be one of the most disabling symptoms. The clinical features range from asymptomatic to life threatening. GBS can be devastating because of its sudden and unexpected onset. GBS commences with progressive muscular weakness of extremities that may lead to paralysis. It spreads rapidly, ascending to involve the cranial nerves. Commences distally but spreads proximally and may involve the bulbar region and the diaphragm. Clinical features may include pain in the back and the legs and weakness beginning in the feet and legs and progressing upwards. Pain in the lower back, buttocks or thighs is common, and is often the earliest of symptoms. The respiratory muscles are affected in about half the cases, and this puts the patient in danger. The tendon reflexes are lost, but may still be preserved in the first hours of the illness. In certain cases, muscle weakness develops so quickly that muscle atrophy doesn’t occur, but hypotonia and areflexia do. Skeletal muscle weakness is the hallmark of most myopathies such as seen in Guillain-Barre syndrome (GBS).

Guillain-Barre syndrome (GBS) is usually easily identified with its typical presentation of ascending weakness and areflexia on examination. The disease is characterized by weakness which affects the lower limbs first, and rapidly progresses in an ascending fashion. 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 periods of hours to days, the arms and facial muscles also become affected. GBS can develop over the course of hours or days, or it may take up to 3 to 4 weeks. Patients usually present a few days to a week after onset of symptoms. GBS may herald the onset of sleepiness in a subset of patients, presenting with mild to moderate fatigue, to ‘extreme somnolence’ (profound sleepiness), to “sleep drunkenness”, such as seen in encephalitis, hydrocephalus, or swelling of the brain. The patient’s voice may change because the vocal chords are affected. Speech may be unintelligible (slurred or whispery), because the various muscles required to form speech are weakened. Deafness is unusual but has been reported. Constipation is often a problem, due to the reduced activity of the intestines, change of diet, weakened stomach muscles that resist efforts by the patient to express the intestinal content. Frequently, the lower cranial nerves may be 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.

The Guillain–Barré syndrome is an immune-mediated, acute, generalized peripheral neuropathy (eg, cranial nerve disorders) that usually causes diffuse (widely dispersed) weakness; peripheral nervous system pathology is visible by the lack of motor response to peripheral nerve stimulation. This syndrome (also called infectious polyneuritis, Landry-Guillain-Barré syndrome, and acute idiopathic polyneuritis) can occur at any age but is most common between ages 30 and 50; it affects both sexes equally. Guillain-Barre Syndrome has three stages. There is a progression phase over several days to several weeks, a plateau phase of similar duration, and then recovery over weeks to months. Onset: Mean 40 years; Seasonal: Higher frequency in Spring (March to May).

The classic Guillain-Barre syndrome is characterized by acute ascending and progressive neuropathy associated with muscle weakness and hyporeflexia. The clinical manifestations of this condition included areflexia in the cranial and spinal nerves as well as apnoea. Cranial nerves are involved in approximately 50% of cases. A special form of the syndrome is the Miller-Fisher syndrome in which signs of the cranial nerve deficit dominate in the first phase of the disease. In rare cases, acute quadriparesis may develop leading to coma and the absence of brainstem reflexes. At first the patient may become unresponsive to light with sluggishly reactive pupils which can rapidly progress to dilated or fixed pupils, usually the result of para sympatholytic or anticholinergic drugs.

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 over exercising. These pains are self-limited and should be treated with standard analgesics. Bladder dysfunction may occur in severe cases but should be transient. If spinal cord disease should be suspected, polyradiculoneuropathy should be considered. 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. Autonomic dysfunction in GBS is manifested as tachycardia and mild hypertension in the acute stage and cardiac arrhythmias associated with autonomic dysfunction are a recognised manifestation in Guillain-Barré syndrome. Marked orthostatic hypotension following paresis suggests an atypical clinical course of GBS. Notably, hypertension and tachycardia are also an indication of awareness and/or pain.

GBS is a rare inflammation of the nerves, caused by the patient’s body producing antibodies against the peripheral nerves. The syndrome affects each patient differently and so the course of the disease differs for each patient. The brain and spinal cord are called the central nervous system (CNS), while nerves throughout the rest of the body are referred to as the peripheral nervous system (PNS). The basic building block of the nervous system is a nerve cell, or neurone. Irritated, inflamed or damaged nerves in the brain, spinal cord or body can cause headache and pain, which points to a causal connection to GBS. Severe headache in Guillain-Barré syndrome is rare; an initial episode of a headache, vomiting, fever and back and limb pain is usually followed by paralysis.

Many secondary complications may follow GBS that include dysautonomia, deep vein thrombosis, anemia, immobilization, and pain and sensory involvement (J. M., Meythaler, 1997; J. M. Meythaler, M. J. De Vivo, and W. C. Braswell, 1997). These medical complications have not been studied systematically, and the psychosocial complication of pain following GBS has certainly been overlooked in the literature. Adverse events may also accompany GBS which may include mild-to-moderate migraine attacks, chills, chest discomfort, fatigue, fever rarely, nausea, wheezing, dizziness, rashes, pains, and tenderness at injection site with increased risk of urticaria, pruritus, or petechiae and renal tubular necrosis in older volume-depleted diabetic patients.

Notably, Guillain-Barré syndrome (GBS) has become the major cause of acute neuromuscular paralysis in the Western world since the near eradication of polio. It is polio’s closest mimic, manifesting as a cold or a mild flu, progressing to extreme fatigue, muscle weakness, debilitating joint pain, breathing difficulties and intolerance of cold. Feeling unusually cold is a common finding in many subjects with GBS. Conditions such as poliomyelitis and other neurological diseases such as Parkinson’s disease that may mimic Guillain-Barré need to be ruled out before the diagnosis is made. Further, variants of GBS have emerged to make GBS a true syndrome rather than a specific disease. Certain viruses which exhibit strong neurotropism and generally thought to be associated with polio-like paralytic syndromes , also share a commonality with aseptic meningitis, including the Guillain Barré Syndrome. GBS can present with focal neurologic deficits or symptoms similar to Parkinsons disease, polio, and West Nile Virus. Several disorders have symptoms similar to those found in Guillain-Barré, so doctors must examine and question patients carefully before making a diagnosis.

GBS mimicking cerebral death has also been reported in the literature, illustrating an extreme polyneuropathy and there are also reports of other conditions that mimic brain death or that provide examples of the mistaken diagnosis of brain death. Fulminant cases of GBS have been reported in which a rapid deterioration evolves to a clinical state resembling “brain death”. Concerns have arisen with respect to the retrieval of organs for transplantation due to inconsistencies in the ethical declaration of brain death for confirming “complete cessation” of brain function and therefore brain death. Organ transplantation is premised on professional and public acceptance that the donor is dead and that the cessation of all brain function persists for an appropriate period of observation. There should be no central nervous system depressant or muscle relaxant drugs present and metabolic, endocrine or hypothermic causes of coma must first be excluded; physical signs may be obscured, or altered by the presence of sedative or muscle relaxant drugs, or due to anoxic ischemic insult. GBS is one of few neurological diseases whose clinical manifestations may be identical to those in brainstem death. Some similarities may also be found in other demyelinating syndromes.

Metabolic impairment causes demyelination or axonal degeneration. Axonal degeneration secondary to severe demyelination may mimic brain death.
Symptoms can range from mild muscle weakness that resolves quickly, to complete muscle paralysis. Subacute and chronic diffuse axonal types (diffuse axonal polyneuropathy) include most toxic and nutritional neuropathies, uremia, diabetes, hypothyroidism, human immunodeficiency virus (HIV) infection, Lyme disease, peroneoplastic disease, dysproteinemia, and amyloidosis. Metabolic processes may also cause diffuse weakness. Metabolic impairment causes demyelination or axonal degeneration.

Caution
Experimental parasitology, ie, testing parasite excretory-secretory products (ESP) as cures to treat Campylobacter jejuni infections is reported in the literature; may provide important clues to GBS triggers.

Acute inflammatory demyelinating polyradiculoneuropathy has a wide spectrum involving all the peripheral and cranial nerves; it can present with the same radiological features of brain tumors even on routine MR imaging., suggestive of growing large mass-like lesions.

Severe axonal GBS will show diffuse loss of sensory and motor responses with widespread active denervation. Axonal degeneration secondary to severe demyelination may mimic brain death. Glasgow Coma Scale should be cautiously applied as a prognostic measure in patients with metabolic or toxic CNS insults.

As a safeguard in determining brain death a number of tests need to be carried out every 6 hours and recorded, the physicians performing this determination must not be part of a transplantation team. In some cases, 48 to 72 hours is required to evaluate brain death and a repeat examinations are required to increase the diagnostic yield with observation up to 24 hours is sometime needed. The length of time between serial examinations to declare brain death varies marginally from 6 to 72 hours.

Clinical variants
Although ascending paralysis is the most common form of spread in GBS, several variants of GBS are recognized. These disorders share similar patterns of evolution, recovery, symptom overlap, and probable immune-mediated pathogenesis.

• Miller Fisher Syndrome (MFS) is a rare variant of GBS 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. In the initial stage of the disease the clinical features characteristic of the MFS may be observed, which is a special type of polyradicular and polyneural Guillaine-Barre syndrome involving mostly the cranial nerves. In its classic form the syndrome consists of external ophthalmoplegia, cerebellar ataxia, weakened reflexes with preserved consciousness and lack of damage to the pyramidal tracts. CT scans of some patients with this syndrome have shown structural damage to the brainstem in the form of decreased density; would show up this way whether the CT scan was done with contrast or not.
• Acute motor axonal neuropathy (AMAN) marked by diffuse weakness refers to the cases showing only motor symptoms; 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. Other variants are notable for an axonal pattern of electrodiagnostic findings and axonal pathology with little inflammation. Recovery is slow and often incomplete.
• Also known as: Kussmaul-Landry syndrome, Landry’s syndrome, Landry-Guillain-Barré syndrome, Landry-Kussmaul syndrome, Glanzmann-Saland syndrome (misnomer).
• Addendum Patients with the pharyngeal-cervical-brachial variant (PCB) of Guillain-Barre syndrome (GBS) have anti-GT1a IgG with or without GQ1b reactivity, whereas those with Miller Fisher syndrome (MFS) or Bickerstaff’s brainstem encephalitis (BBE) have anti-GQ1b IgG antibodies which cross-react with GT1a. The presence of a common autoantibody (anti-GT1a IgG) and overlapping illnesses suggests that PCB is closely related not only to GBS but to MFS and BBE as well.

Rauschka, H., K. Jellinger, et al. (2003). “Guillain-Barre syndrome with marked pleocytosis or a significant proportion of polymorphonuclear granulocytes in the cerebrospinal fluid: neuropathological investigation of five cases and review of differential diagnoses.” Eur J Neurol 10(5): 479-86 In summary “the presence of polymorphonuclear granulocytes does not rule out the diagnosis of GBS”.

During the 1999 New York City West Nile virus (WNV) outbreak, 4 patients with profound muscle weakness, attributed to Guillain-Barré syndrome, were autopsied. These cases were the first deaths caused by WNV. Both Guillain-Barré disease and aseptic meningitis were diagnosed as polio during the US epidemics prior to 1957.

In September 2006 Guillian-Barré-type symptoms were observed on patients at Panama City’s big public hospital. The patients, who showed signs of weakness or tingling sensation in the legs, did not develop the characteristic spread upwards of paralysis. The reason was found later in a poisoned medicine Lisinopril in which the glycerin excipient had been illegally replaced by diethylene glycol. (See Sources below)

Diagnosis
Patients often appear to be nauseated and in a state of total exhaustion.

The diagnosis is based on a clinical examination of the symptoms and their distribution and is dependent 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. The diagnosis of Guillain-Barre syndrome is also based on clinical features and albumin cytological dissociation present in the spinal fluid. CBC shows leukocytosis and a shift to immature forms early in the illness. Cases of Guillain-Barre syndrome can have pleocytosis or CSF granulocytes.

Severe forms of GBS may result in urinary or fecal incontinence. A history of grossly bloody stools may be observed; fecal leukocytes are usually present. Toxic megacolon, pseudomembranous colitis, massive lower gastrointestinal hemorrhage, mesenteric adenitis, and appendicitis also have been described in immunocompetent patients with C jejuni infection.

GBS associated with marked migraine headache is a rare finding and one seldom reported in the literature, (see Brian Claman, Notable Patients below).
Review recent medical history; many cases are linked with recent bacterial or viral infections, vaccinations or surgeries. Infection with campylobacter, a bacteria found in undercooked food, especially poultry, may predispose Guillaine-Barre Syndrome.

A clinical feature of demyelination is muscle weakness without muscle atrophy.

Note any difficulty with facial muscles or movement, such as trouble moving your eyes, slow speech and problems chewing or swallowing.

Assess both sides of the body. Guillain-Barre Syndrome affects both sides, unlike a stroke. Strokes generally paralyze only one side.

Evaluate and report any changes in bladder or bowel function. Guillain-Barre Syndrome impacts the muscles that control bladder and intestinal function.
Pay attention to unusual or severe lower back pain, which can signal Guillain-Barre Syndrome.

Signs of hypotonia: Hypotonia is an abnormally severe loss of muscle tone. The muscles feel soft and doughy.

Weakening of diaphragm: Monitor for shallow or rapid breathing (breathing may be labored and difficult); patients with neuromuscular disorders have rapid shallow breathing secondary to severe muscle weakness or abnormal motor neuron function. Many people with the syndrome are temporarily placed on ventilators in order to breathe.

Gasping for breath – sleep apnea: GBS can freeze the breathing muscles with assault on muscle function resulting in episodic and paroxysmal disorders with progression. Snoring and sleep apnea are part of the same problem. Look at the shape of the neck. Adults and older adolescents having short thick necks are at greater risk of developing obstructive sleep apnoea. Aspiration and respiratory failure are major concerns.

GBS may induce a “locked-in” state of ‘outer calm inner panic’ due to a severely paralyzed motor function that patients are able to recall vividly and unpleasantly. The locked-in state involves damage to corticospinal and corticobulbar pathways in the basis pontis. GBS causes bilateral profound damage to these pathways with diffuse compromise to peripheral nerves.

Hypoventilation secondary to respiratory muscle weakness may be observed.

Dysautonomia, often causing profound swings in blood pressure (hypotension alternating with hypertension), are often conspicuous in patients with Guillain-Barré. There is even a panic factor marked by sudden onset of intense apprehension, fear, terror, or impending doom with awareness. In GBS, dysautonomia is usually acute and reversible.

Coagulopathy: blood clotting disorders, (blood thinners may be needed to prevent blood clots).

ECG may show heart problems in some cases.

NCV (nerve conduction velocity) shows nerve damage.

EMG tests the electrical activity in muscles. It may show that nerves do not react properly to stimulation.

Confounders
Guillain-Barre Syndrome and its complications are unclear or arbitrary. Data contain little information on potential confounders, such as co-medication, including underlying diseases (eg, diabetes mellitus) and potentially confounding coincidental infections (eg, Campylobacter). Failure to recognize the separate variants may confound the clinical picture. Some of the same diseases that mimic radiographic findings also can confound the diagnostic interpretation of CT scans.

GBS may also develop secondary to untreated or inappropriately treated conditions (infections have severe systemic complications), drug side effect causes, “shotgun therapy” that inflicts collateral damage and drug interaction causes. CNS underlying disorders, poorly controlled insulin-dependent diabetes mellitus or cancer, encephalitis, meningitis, abscess , subdural hematoma, S.aureus endocarditis, spinal epidural haematoma, trauma, stroke, including acute intermittent porphyria in association with or which may mimic GBS suggest that infectious or metabolic triggers may also predispose and electrolyte imbalances may further confound the neurologic examination.

Transient diabetes has been observed in certain cases of Guillain-Barré syndrome. Hypokalemic periodic paralysis is one of the many disorders which, if left untreated may also mimic GBS. Several potential confounders, including diseases putatively associated with peripheral neuropathy; overlapping and/or underlying illness may confound the diagnosis of GBS. Early literature emphasised the high prevalence of gastrointestinal symptoms in patients with diabetes complicated by neuropathy. The reduction in the odds of neuropathy due to glycemic control is attenuated with increasing duration. Glycemic triggers may be prevented by maintaining appropriate blood glucose levels.

Drug intoxication is the most common cause of coma of rapid onset which may mimic brain death; examination can be marred by the effects of sedation. Metabolic derangement and endocrine crisis can also mimic brain death. More dramatic is the reversible Guillain–Barré syndrome involving all the peripheral and cranial nerves. The progression which can mimic brain death occurs over a period of days.

Obtundation in GBS: The term refers to a reduction in alertness and arousal in which these patients appear to be completely unresponsive. Although patients with GBS in the setting of preserved consciousness may be described as obtunded, patients may be fully lucid; ambiguities in deciding whether some individual patients are truly unconscious, in a vegitative state, or simply locked-in (implies fully preserved consciousness) cannot be diagnosed on the basis of a paltry CT.

Influence of tranquillisers (drugs that slow normal brain function), sedatives (drugs that have a depressant effect on the central nervous), narcotics (drugs that induce sleep), and neuroleptics (drugs that block dopamine receptors).

Laboratory Findings

• Leukocytosis – early
• CSF – typical CSF findings include an elevated protein level (100 – 1000 mg/dL) without an accompanying pleocytosis (increased cell count).
• Coagulation – GBS presents with elevated fibrinogen and is typically elevated at presentation. CSF usually clots in the presence of increased fibrinogen.
• Acute phase reactant – marker of inflammation. Falls as syndrome resolves with treatment.
• pleocytosis – Sustained pleocytosis may indicate an alternative diagnosis such as infection. The diagnosis is confirmed by the presence of Albuminocytological dissociation in the CSF. CSF – (50 mg/dl – 100 mg/dl) – this reflects the widespread inflammation of the nerve roots; the protein increase usually begins after the 10th day of the neurologic illness and peaks at 4 wk-6wk; the increase parallels the clinical severity
• Complete blood count – Normal cell count (90% of patients); slightly increased mononuclear cells (10% of patients)
• Electrophysiological studies show demyelinating signs with decreased conduction velocity and normal amplitude of motor potentials in Guillain-Barré syndrome versus normal conduction velocity and reduced amplitude of motor potentials in axonal polyneuropathy.
• Electrodiagnostics – electromyography (EMG) and nerve conduction study (NCS) 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

One of the clinical features of GBS is elevated protein levels in the CSF fluid evinced on the spinal tap.

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

The possibility of West Nile Virus (WNV) meningoencephalitis should be entertained in the setting of suspected Guillain-Barré syndrome, as management of the two entities is markedly divergent.

A noteworthy diagnostic dilemma which may mimic GBS is botulism, in which the differential diagnosis includes organophosphate ingestion, tick paralysis, brainstem tumor, poliomyelitis, and myasthenia gravis.

Treatment
Treatment modalities used for patients with GBS include anticoagulation, IVIG, plasmapheresis, and high-dose corticosteroids.

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 initiated as soon as possible. Either high-dose intravenous immunoglobulins (IVIg) at 400 mg/kg for 5 days 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 (.4 kg each day). 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 (PE) 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 patient 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 separate 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
Approximately 80% of patients have a complete recovery within a few months to a year, although minor findings 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 runs 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).

About 70 to 80% of patients make a good recovery with little or no residual neurologic signs. Others have varying degrees of distal muscle wasting and weakness.

Demyelination as evidenced by slow condution velocity and conduction block are reversible features of the disease.

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.

Evidence of West Nile encephalitis virus (polio-like) infection has been documented in most states of the continental United States within a short period of its first introduction in 1999. Health care providers are mostly aware of the usual presentations of this disease, eg, aseptic meningitis, encephalitis and Guillain-Barré syndrome.

Central nervous system complications of many pharma-agents include aseptic meningitis and Guillain-Barré syndrome.

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

The antigenic similarity between specific regions (terminal tetrasaccharide) of lipopolysaccharide (LPS) of C jejuni and human gangliosides (GM1) led to the concept of “molecular mimicry.”

Notable Patients

• Joseph Heller, author of Catch-22. His experiences with the illness make up a large portion of his non-fiction book No Laughing Matter.
• Andy Griffith, actor on Andy Griffith Show, and Matlock. He contracted Guillain-Barré in 1983. [1]
• Rachel Chagall, actress, contracted GBS in 1982. In 1987 she portrayed Gabriela Brimmer, a notable disabilities activist.[2]
• Franklin D. Roosevelt, U.S. president. In 2003, a peer-reviewed study[1] found that it was more likely that Roosevelt’s paralytic illness was actually Guillain-Barré syndrome, not poliomyelitis. See separate article on Franklin D. Roosevelt’s paralytic illness.
• Scott Klopfenstein, backup vocals, trumpet player, 2nd guitar, and keyboard player for Reel Big Fish.
• Tony Benn Retired cabinet minister
• Morten Wieghorst, former footballer, most known for playing for Celtic FC
• Markus Babbel, ex-Bayern Munich & Liverpool footballer and German international.
• Michael P. Moran, an American actor.
• Jack Rohan, an American basketball player.
• Jamie Brooks, an English football player.

In Popular Culture
Guillain-Barré is recognized today in the media on the show House. When a patient on this popular American television program expresses certain symptoms in the lower legs, the characters—Dr. Chase, Cameron and Foreman—often diagnose him with Guillain-Barré. The brief statements add to the entertainment value of the show while also spreading awareness of the illness. A notable fictional patient is Michael Tolliver in the book Tales of the City, his disease and fear of the paralysis spreading to his lungs forming a major part of the plot.

Genova Diagnostics: May 12, 1999, Volume 4, Number 9 “We are too much accustomed to attribute to a single cause that which is the product of several, and the majority of our controversies come from that.” Baron Justus von Liebig (1803-73).

See also

• Peripheral neuropathy
• The Myolin Project

Sources

• The New York Times May 6 2007, Article by Walt Bogdanich and Jake Hooker.[3]
• Journal of Neurosurgical Anesthesiology – Fulltext: Volume 16(4 – Abstract: colon; Severe headache in Guillain-Barre syndrome…[4]
• All About Guillain-Barré Syndrome, S. Marcussen. [5]Symptoms & the way patients experience them.
• eMedicine – Serum Sickness : Article by Hassan M Alissa, MD [6] Neurologic complications.
• eMedicine – Guillain-Barre Syndrome : Article by Heather Rachel Davids, MD [7] Clinical: Section 3 of 10.
• Brain Death: C.J. Doig MD MSc, E. Burges, MD, [8] Inconsistencies in ethical declaration.
• Prodromal Malaise in GBS: [9] GP notebook tracker.
• Trip Database [10] Evidence Based Medicine (EBM) Search GBS
• PubMed [11] Fulminant Guillain-Barré syndrome mimicking cerebral death: case report and literature review.
• Dysautonomia in GBS: [12] When the Autonomic Nervous System or Body’s Autopilot Fails
• Campylobacter jejuni [13] in Waterborne Protozoa.

References

^ Goldman, AS et al, What was the cause of Franklin Delano Roosevelt’s paralytic illness?. J Med Biogr. 11: 232-240 (2003)

External links

• GBS/CIDP Foundation International – information and support
• Guillain-Barré Syndrome Support Group (UK)
• Miller Fisher’s syndrome at Who Named It
• miller_fisher at NINDS
• -1395654646 at GPnotebook

Synonyms and related keywords: Guillain-Barré syndrome, GBS, acute inflammatory demyelinating polyneuropathy, AIDP, acute motor axonal neuropathy, AMAN, acute motor-sensory axonal neuropathy, AMSAN, Miller-Fisher syndrome, MFS, acute panautonomic neuropathy, pharyngeal-brachial-cervical variant, pure sensory variant, Campylobacter jejuni, acute placid paralysis.

Author: Andrew Miller, MD, Clinical Assistant Instructor, Departments of Emergency Medicine and Internal Medicine, State University of New York Downstate Medical Center, Kings County Hospital Center
Coauthor(s): Omar E Ali, MD, Staff Physician, Department of Internal Medicine, SUNY Downstate Medical Center, Brooklyn/Kings County Hospital Center; Richard Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center

Andrew Miller, MD, is a member of the following medical societies: American College of Physicians, American Medical Association, Islamic Medical Association of North America, and Medical Society of the State of New York

Editor(s): Edward A Michelson, MD, Program Director, Associate Professor, Department of Emergency Medicine, University Hospital Health Systems in Cleveland; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; J Stephen Huff, MD, Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health System; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Steven C Dronen, MD, FAAEM, Director of Emergency Services, Director of Chest Pain Center, Department of Emergency Medicine, Ft Sanders Sevier Medical Center.

Background: In 1859, Landry published a report on 10 patients with an ascending paralysis. This was followed by a report in 1916 written by 3 French physicians working in the Sixth Army camp during the First World War; they described 2 French soldiers with motor weakness, areflexia, and albuminocytological dissociation in the cerebrospinal fluid. In this report Guillain, Barré, and Strohl carefully recorded and interpreted the tendon reflexes of their patients and became the first to recognize the peripheral nature of the illness. Further cases were recognized, and the identified syndrome was later named Guillain-Barré syndrome (GBS). Historically, GBS was a single disorder; however, current practice divides the syndrome into several variant forms.

GBS is a heterogeneous grouping of immune-mediated processes generally characterized by motor, sensory, and autonomic dysfunction. In its classic form, GBS is an acute inflammatory demyelinating polyneuropathy characterized by progressive symmetric ascending muscle weakness, paralysis, and hyporeflexia with or without sensory or autonomic symptoms; however, variants involving the cranial nerves or pure motor involvement are not uncommon. In severe cases, muscle weakness may lead to respiratory failure, and labile autonomic dysfunction may complicate the use of vasoactive and sedative drugs.

Pathophysiology: Although the clinical syndrome classically presents as a rapidly progressive acute polyneuropathy, several pathologic and etiologic subtypes exist. Most patients with GBS exhibit absent or profoundly delayed conduction in action nerve fibers. This aberrant conduction results from demyelination of nerve cell axons. Peripheral nerves and spinal roots are the major sites of demyelination, but cranial nerves also may be involved.
GBS is believed to result from an autoimmune response, both humoral and cell mediated, to a recent infection or any of a long list of medical problems. Its relation to antecedent infections and the identification of various antiganglioside antibodies suggest that molecular mimicry may serve as a possible mechanism for the disease. The antibodies formed against gangliosidelike epitopes in the lipopolysaccharide layer of some infectious agents have been shown in both necropsy and animal models to cross-react with the ganglioside surface molecules of peripheral nerves. Symptoms generally coincide pathologically with various patterns of lymphocytic infiltration and macrophage-mediated demyelination, depending on the subtype in question. Recovery is typically associated with remyelination. In a subset of patients, GBS is associated primarily with myelin-sparing axonal damage resulting from a direct cellular immune attack on the axon itself.
The acute inflammatory demyelinating polyneuropathy (AIDP) subtype of GBS is by far the most commonly identified form in the United States. It is generally preceded by an antecedent bacterial or viral infection. Nearly 40% of patients are seropositive for Campylobacter jejuni. Lymphocytic infiltration and macrophage-mediated demyelination of the peripheral nerves are present. Symptoms generally resolve with remyelination.

The acute motor axonal neuropathy (AMAN) subtype is a purely motor subtype, which is more prevalent amongst pediatric age groups. Nearly 70-75% of patients are seropositive for Campylobacter. One third of these cases may actually be hyperreflexic. AMAN is generally characterized by a rapidly progressive weakness, ensuing respiratory failure, and good recovery.

Acute motor-sensory axonal neuropathy (AMSAN) is an acute severe illness similar to AMAN except that AMSAN also affects sensory nerves and roots. Patients are typically adults with both motor and sensory dysfunction, marked muscle wasting, and poor recovery. The hyperreflexia mechanism associated with AMAN is not known, but dysfunction of the inhibitory system via spinal interneurons may increase motor neuron excitability.

Miller-Fisher syndrome (MFS) is a rare variant that typically presents with the classic triad of ataxia, areflexia, and ophthalmoplegia. The ataxia tends to be out of proportion to the degree of sensory loss. Patients may also have mild limb weakness, ptosis, facial palsy, or bulbar palsy. Anti-GQ1b antibodies are prominent in this variant, and patients have reduced or absent sensory nerve action potentials and absent tibial H reflex. Recovery generally occurs within 1-3 months.

Acute panautonomic neuropathy is among the rarest of all variants and involves both the sympathetic and parasympathetic nervous systems. Cardiovascular involvement is common, and dysrhythmias are a significant source of mortality in this form of the disease. The patient may also experience sensory symptoms. Recovery is gradual and often incomplete.

Frequency:

In the US: The incidence is 1-3 per 100,000 inhabitants, making GBS the most common cause of acute flaccid paralysis in the United States.
Internationally: AMAN is a purely motor form that occurs mainly in northern China but is also more common in developing nations.
AIDP accounts for up to 90% of cases in Europe, North America, and the developed world.

Epidemiologic studies from Japan indicate that in this region a greater percentage of GBS cases are associated with antecedent C jejuni infections and a lesser number are related to antecedent cytomegalovirus infections when compared with their North American and European counterparts.

Mortality/Morbidity: Most patients (up to 85%) with GBS achieve a full and functional recovery within 6-12 months. Recovery is maximal by 18 months past onset.

Patients may have persistent weakness, areflexia, imbalance, or sensory loss. Approximately 7-15% of patients have permanent neurologic sequelae including bilateral footdrop, intrinsic hand muscle wasting, sensory ataxia, and dysesthesia.
The mortality rate varies but may be less than 5% in tertiary care centers with a team of medical professionals who are familiar with GBS management. Causes of death include adult respiratory distress syndrome, sepsis, pneumonia, pulmonary emboli, and cardiac arrest.
Despite intensive care, 3-8% of patients die.
Race: No racial preponderance exists.

Sex: The male-to-female ratio is 1.5:1. A Swedish epidemiologic study indicated that the incidence of GBS is lower during pregnancy and increases in the months immediately following delivery.

Age: GBS occurs at all ages, but a bimodal distribution with peaks in young adulthood (15-35 y) and in elderly persons (50-75 y) appears to exist. Rare cases have been noted in infants.

History: The typical GBS patient (likely AIDP) presents 2-4 weeks after a relatively benign respiratory or gastrointestinal illness complaining of dysesthesias of the fingers and lower extremity proximal muscle weakness. The weakness may progress over hours to days to involve the arms, truncal muscles, cranial nerves, and muscles of respiration. The illness progresses from days to weeks, with the mean time to the nadir of clinical function being 12 days and 98% of patients reaching a nadir by 4 weeks. A plateau phase of persistent, unchanging symptoms then ensues followed days later by gradual symptom improvement. The mean time to improvement and clinical recovery are 28 and 200 days, respectively.

Up to one third of patients require mechanical ventilation during the course of their illness. Causes for this include cranial nerve involvement affecting airway maintenance and respiratory muscle paralysis.
Motor dysfunction
Symmetric limb weakness typically begins as proximal lower extremity weakness and ascends to involve the upper extremities, truncal muscles, and head.
Inability to stand or walk despite reasonable strength, especially when ophthalmoparesis or impaired proprioception is present.
Respiratory muscle weakness with shortness of breath may be present.
Cranial nerve palsies (III-VII, IX-XII) may be present. Patients may present with facial weakness mimicking Bell palsy, dysphagia, dysarthria, ophthalmoplegia, and pupillary disturbances. The Miller-Fisher variant is unique in that this subtype begins with cranial nerve deficits.
Lack of deep tendon reflexes is a hallmark sign.
Sensory dysfunction
Paresthesia generally begins in the toes and fingertips and progresses upward but generally not extending beyond the wrists or ankles.
Pain is most severe in the shoulder girdle, back, buttocks, and thighs and may occur with even the slightest movements.
Loss of vibration, proprioception, touch, and pain distally may be present.
Autonomic dysfunction
Cardiovascular signs may include tachycardia, bradycardia, dysrhythmias, wide fluctuations in blood pressure, and postural hypotension.
Urinary retention due to urinary sphincter disturbances may be noted.
Constipation due to bowel paresis and gastric dysmotility may be present.
Facial flushing and venous pooling secondary to abnormal vasomotor tone may be present.
Hypersalivation
Anhydrosis
Tonic pupils
Papilledema secondary to elevated intracranial pressure is present in rare cases.
Physical:

Vital signs
Patients may have tachycardia or bradycardia, hypertension or hypotension, or hyperthermia or hypothermia.
Low oxygen saturation may be present with advanced respiratory muscle involvement.
Cranial nerves: Patients may present with facial weakness mimicking Bell palsy, dysphagia, dysarthria, ophthalmoplegia, and pupillary disturbances.
Dysreflexia
Patients with manifest weakness are invariably hyporeflexic or areflexic in the involved areas.
Respiratory symptoms
Poor inspiratory effort or diminished breath sounds
Motor
Symmetric limb weakness typically begins as proximal lower extremity weakness and ascends to involve the upper extremities, truncal muscles, and head.
Inability to stand or walk despite reasonable strength, especially when ophthalmoparesis or impaired proprioception is present.
Hypotonia
Wasting of limb muscles is not an acute finding.
Abdominal
Paucity or absence of bowel sounds suggests paralytic ileus.
Suprapubic tenderness or fullness may be suggestive of urinary retention.
Sensory: Patients may experience numbness, paresthesias, impaired proprioception, and pain.
Papilledema secondary to elevated intracranial pressure is present in rare cases.
Causes: GBS has been associated with antecedent bacterial and viral infections, administration of certain vaccinations, and other systemic illnesses. Case reports exist regarding numerous medications and procedures; however, whether any causal link exists is unclear.

Bacterial infections include C jejuni, Haemophilus influenzae, Mycoplasma pneumoniae, and Borrelia burgdorferi.
Viral infections include cytomegalovirus, Ebstein-Barr virus, and during seroconversion with the human immunodeficiency virus (HIV).
Vaccines
A study reviewing the cases of GBS during the 1992-1993 and 1993-1994 influenza seasons found an adjusted relative risk of 1.7 cases per 1 million influenza vaccinations.
Epidemiologic studies from Finland, southern California, and Latin America failed to validate an earlier retrospective study from Finland suggesting a cause-effect relationship between oral polio vaccination and GBS.
Data from 2 large-scale epidemiologic studies found that fewer cases of GBS occurred following administration of tetanus toxoid containing vaccinations than occurred in the baseline population.
Two epidemiologic studies failed to show any conclusive epidemiologic association between GBS and the hepatitis B vaccine.
A large Latin American study of more than 2000 children with GBS following a mass measles vaccination program in 1992 and 1993 failed to establish a statistically significant causal relationship between administration of the measles vaccine and GBS.
A recent report from the Centers for Disease Control and Prevention (CDC) suggests that an increased incidence of GBS may exist amongst recipients of the Menactra meningococcal conjugate vaccine.
Case reports exist regarding group A streptococci vaccines, the rabies vaccine, and the swine flu vaccine; however, conclusive statistically significant evidence is lacking.
Medications
A case-controlled study showed that patients with GBS had used antimotility drugs and penicillins more often and oral contraceptives less often. No definite cause-effect relationship has been established.
Case reports exist regarding streptokinase, isotretinoin, danazol, captopril, gold, heroin, and epidural anesthesia among others.
Anecdotal associations include systemic lupus erythematosus, sarcoidosis, lymphoma, surgery, renal transplantation, and snake bites.
CBRNE – Botulism
Cauda Equina Syndrome
Diphtheria
Encephalitis
Hyperkalemia
Hypokalemia
Hypophosphatemia
Meningitis
Myasthenia Gravis
Polymyositis
Spinal Cord Infections
Spinal Cord Injuries
Systemic Lupus Erythematosus
Tick-Borne Diseases, Lyme
Toxicity, Alcohols
Toxicity, Heavy Metals
Toxicity, Organophosphate and Carbamate

Other Problems to be Considered:
Basilar artery occlusion
Chronic inflammatory demyelinating polyneuropathy
Folate deficiency
Hereditary neuropathies
Neoplasia
Neurotoxic fish poisoning
Poliomyelitis
Porphyria
Sarcoid meningitis
Spinal cord compression
Spinal cord syndromes, particularly postinfection
Tick paralysis
Transverse myelitis
Vitamin B-12 deficiency

Lab Studies:

Diagnosis usually is made on clinical grounds. Laboratory studies are useful to rule out other diagnoses and to better assess functional status and prognosis.
Lumbar puncture and spinal fluid analysis
Elevated or rising protein levels on serial lumbar punctures and 10 or fewer mononuclear cells/mm3 strongly support the diagnosis.
Most, but not all, patients have an elevated CSF protein level (>400 mg/L), with no elevation in CSF cell counts.
Normal CSF protein level does not rule out GBS because the CSF protein level remains normal in 10% of patients and because any rise in the CSF protein level may not be observed until 1-2 weeks after the onset of weakness.
CSF pleocytosis is well recognized in HIV-associated GBS.
Biochemical screening
Biochemical screening includes electrolyte levels; liver function tests (LFTs); CPK level; erythrocyte sedimentation rate (ESR); antiganglioside antibodies; and antibodies to C jejuni, cytomegalovirus, Ebstein-Barr virus, herpes simplex virus (HSV), HIV, and M pneumoniae.
Syndrome of inappropriate antidiuretic hormone (SIADH) occurs in some patients with GBS.
LFT results are elevated in up to one third of patients.
CPK and ESR may be elevated with myopathies or systemic inflammatory conditions.
Patients with the Miller-Fisher variant may have anti-GQ1b antibodies.
Patients who have antibody subtype GM1 may have poorer prognoses.
Stool culture for C jejuni
Pregnancy test
Imaging Studies:

MRI
MRI is a sensitive but nonspecific test.
Spinal nerve root enhancement with gadolinium is a nonspecific feature seen in inflammatory conditions and is caused by disruption of the blood-nerve barrier.
Selective anterior nerve root enhancement appears to be strongly suggestive of GBS.
The cauda equine nerve roots are enhanced in 83% of patients.
Other Tests:

Forced vital capacity
Forced vital capacity (FVC) is very helpful in guiding disposition and therapy.
Patients with an FVC less than 15-20 mL/kg, maximum inspiratory pressure less than 30 cm H2O, or a maximum expiratory pressure less than 40 cm H2O generally progress to require prophylactic intubation and mechanical ventilation.
Nerve conduction studies
A delay in F waves is present, implying nerve root demyelination.
Nerve motor action potentials may be decreased. This is technically difficult to determine until the abnormality is severe.
Compound muscle action potential (CMAP) amplitude may be decreased.
Frequently, patients show evidence of conduction block or dispersion of responses at sites of natural nerve compression. The extent of decreased action potentials correlates with prognosis.
Prolonged distal latencies may be present.
Rarely neurophysiologic testing is normal in patients with GBS. This is believed to be due to the location of demyelinating lesions in proximal sites not amenable to study.
Muscle biopsy may help to distinguish GBS from a primary myopathy in unclear cases.
Many different abnormalities may be seen on ECG, including second-degree and third-degree atrioventricular (AV) block, T-wave abnormalities, ST depression, QRS widening, and a variety of rhythm disturbances.
Procedures:

Lumbar puncture and spinal fluid analysis
Prehospital Care:

ABCs, IV, oxygen, and assisted ventilation may be indicated.
Monitor for cardiac arrhythmias.
Transport expeditiously.
Emergency Department Care:

ABCs, IV, oxygen, and assisted ventilation may be indicated.
Intubation should be performed on patients who develop any degree of respiratory failure. Clinical indicators of the need for intubation include hypoxia, rapidly declining respiratory function, poor or weak cough, and suspected aspiration. Typically, intubation is indicated whenever the FVC is less than 15 mL/kg.
Patients who have, or are suspected of having, GBS should be monitored closely for changes in blood pressure, heart rate, and other arrhythmias.
Treatment rarely is needed for tachycardia.
Atropine is recommended for symptomatic bradycardia.
Because of the lability of dysautonomia, hypertension is best treated with short-acting agents, such as a short-acting beta-blocker or nitroprusside.
Hypotension of dysautonomia usually responds to intravenous fluids and supine positioning.
Temporary pacing may be required for patients with second-degree and third-degree heart block.
Consultations:

Consult a neurologist if any uncertainty exists as to the diagnosis.
Consult the ICU team for evaluation of need for admission to the unit.

Only plasma exchange therapy and intravenous immune serum globulin (IVIG) have proven effective. Both therapies have been shown to shorten recovery time by as much as 50%. The cost, difficulty, and efficacy of the 2 treatments are comparable.

Corticosteroids are ineffective as monotherapy. Limited evidence shows that oral corticosteroids significantly slow recovery from GBS. Substantial evidence shows that intravenous methylprednisolone alone does not produce significant benefit or harm. In combination with IVIG, intravenous methylprednisolone may hasten recovery but does not significantly affect the long-term outcome.

Immunoadsorption is an alternative that is still in the early stages of evaluation. A small prospective study showed no difference in outcome between patients treated with immunoadsorption and those treated with plasma exchange.

Interferon beta was not associated with significant clinical improvement compared with controls in a small randomized control trial.

Simple analgesics or nonsteroidal anti-inflammatory drugs may be tried but often do not provide adequate pain relief. Single small randomized controlled trials support the use of gabapentin or carbamazepine in the intensive care unit for the treatment of pain in the acute phase of GBS. Adjuvant therapy with tricyclic antidepressant medication, tramadol, gabapentin, carbamazepine, or mexiletine may aid in the long-term management of neuropathic pain.

Time to development of deep vein thrombosis (DVT) or pulmonary embolism (PE) varies from 4-67 days following symptom onset. DVT prophylaxis with gradient compression hose and subcutaneous low molecular weight heparin (LMWH) may cause a dramatic reduction in the incidence of venous thromboembolism, one of the major sequela of extremity paralysis.

True gradient compression stockings (30-40 mm Hg or higher) are highly elastic, providing a gradient of compression that is highest at the toes and gradually decreases to the level of the thigh. This reduces capacity venous volume by approximately 70% and increases the measured velocity of blood flow in the deep veins by a factor of 5 or more.

The ubiquitous white stockings known as antiembolic stockings or thromboembolic disease (TED) hose produce a maximum compression of 18 mm Hg and rarely are fitted in such a way as to provide adequate gradient compression. They have not been shown to be effective as prophylaxis against thromboembolism.

Drug Category: Blood product derivatives — These agents are used to improve the clinical and immunologic aspects of the disease. They may decrease autoantibody production and increase solubilization and removal of immune complexes.

Drug Category: Fractionated low molecular weight heparins — These agents are used in the prophylaxis of DVT. Fractionated LMWH first became available in the United States as enoxaparin (Lovenox). LMWH has been used widely in pregnancy, although clinical trials are not yet available to demonstrate that it is as safe as unfractionated heparin.

Reversible elevation of hepatic transaminase levels occurs occasionally. Heparin-associated thrombocytopenia has been observed with fractionated low molecular weight heparin.

Further Inpatient Care:

Admission to the ICU should be considered for all patients with labile dysautonomia, an FVC of less than 20 mL/kg, or severe bulbar palsy.
Any patients exhibiting clinical signs of respiratory compromise, in any degree, also should be admitted to an ICU.
The risk of sepsis and infection can be decreased by use of minimal sedation, frequent physiotherapy, and mechanical ventilation with positive end expiratory pressure where appropriate.
The risk of DVT and pulmonary embolus may be minimized by administration of heparin or a low molecular weight heparin and intermittent pneumatic compression devices.
The use of cardiac telemetry and pacing in the case of severe bradycardia may help to reduce the risk of cardiac morbidity and mortality.
Pain may be symptomatically improved by frequent passive limb movements, gentle massage, frequent position changes, and use of carbamazepine and gabapentin.
Narcotics should be used judiciously because patients may already be at risk for ileus.
Further Outpatient Care:

Physical therapy and occupational therapy may be beneficial in helping patients to regain their baseline functional status.
Transfer:

Transfer may be appropriate if a facility does not have the proper resources to care for patients who may require prolonged intubation or prolonged intensive care.
Complications:

With modern methods of respiratory management, most complications result from long-term paralysis. Possible complications include the following:
Persistent paralysis
Respiratory failure, mechanical ventilation
Hypotension or hypertension
Thromboembolism, pneumonia, skin breakdown
Cardiac arrhythmia
Ileus
Aspiration
Urinary retention
Psychiatric problems such as depression and anxiety
Prognosis:

Poor prognosis is associated with rapid progression of symptoms, advanced age, prolonged ventilation (>1 mo), and severe reduction of action potentials on neuromuscular testing.
Published reports indicate full recovery may be expected in 50-95% of cases.
Neurologic sequelae
Reported incidence of permanent neurologic sequelae ranges from 10-40%.
The worst-case scenario is tetraplegia within 24 hours with incomplete recovery after 18 months or longer.
The best-case scenario is mild difficulty walking, with recovery within weeks.
The usual scenario is peak weakness in 10-14 days with recovery in weeks to months. Average time on a ventilator (without treatment) is 50 days.
Mortality
Most is due to severe autonomic instability or from the complications of prolonged intubation and paralysis.
Mortality rates range from 5-10%.
Patient Education:

For excellent patient education resources, visit eMedicine’s Brain and Nervous System Center. Also, see eMedicine’s patient education article Guillain-Barré Syndrome.
Medical/Legal Pitfalls:

Failure to anticipate dysrhythmias and autonomic instability
Failure to anticipate progressive respiratory failure
Failure to correctly diagnose GBS in patients with a variant form of the disease or in those with a normal CSF protein
Failure to provide adequate DVT prophylaxis in a patient that develops a DVT and/or pulmonary embolism.
Special Concerns:

The leading cause of death in elderly patients with GBS is arrhythmia.
Recurrence is rare but has been reported in 2-5% of patients.
Variants may present with pure motor dysfunction or acute dysautonomia.
The Miller-Fisher syndrome is a variant of GBS in which the initial symptoms include ataxia, ophthalmoplegia, and areflexia