What is Guillain-Barré syndrome and what are its symptoms and causes?

The name Guillain-Barré syndrome is an older name for the picture of a neurological disease that presents as an acute-onset flaccid paralysis of the body.

The very first mention of this disorder was by Landry in 1859. Later, in 1916, Guillain, Barré and Strohl refined the clinical description of the symptoms and were also the first to discover the characteristic liquor findings.

Today, the modern name acute inflammatory demyelinating polyradiculopathy (AIDP) is used.

This disease is immunologically mediated. It involves dysregulation of the immune system with a propensity for autoimmune reactions directed against the tissues of the body's own nervous system.

Polyradiculoneuropathies can be classified as acute or chronic according to the clinical time course.

Based on the constellation of symptoms and electrophysiological findings (by EMG examination), they are classified into one of several GBS variants.

The following subtypes belong to the group of diseases with a GBS picture:

• acute inflammatory demyelinating polyradiculopathy (AIDP)
• acute motor axonal neuropathy (AMAN)
• acute motor and sensory axonal neuropathy (AMSAN)
• Miller-Fisher syndrome (MFS)
• acute sensory neuropathy and acute pandysautonomia

The most common type of GBS is acute inflammatory demyelinating polyradiculopathy (AIDP). In this type, the maximum symptoms appear within a few days (maximum 4 weeks).

This is followed by a stabilisation of symptoms, the so-called plateau phase, after which the clinical condition gradually improves.

In the differential diagnosis, it is essential to distinguish chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The disease is slower, progressive or relapses.

Axonal variants of GBS can be purely motor or combined sensory and motor neuropathies. Both variants can present as very severe disease with only partial recovery.

With the decline of acute poliomyelitis (an infectious viral disease causing limb paralysis), GBS has become the most common acute paralytic disease in the Western world.

The incidence of GBS is approximately 1 to 2 cases per 100 000 inhabitants per year. It affects more men than women, at a ratio of 3:2. It is more common in the elderly but can also occur in young individuals.

GBS is often associated with vaccination. Increased incidence of the disease has so far only been confirmed in association with rabies vaccination. The rabies vaccine contains material from the brain.

The probability of GBS is reported to be one in 1000 vaccinated persons.

Up to 80% of patients with GBS had infectious disease of the respiratory (58%) or gastrointestinal tract (22%) several weeks before the onset of symptoms. Therefore, most attention has been paid to the postinfectious theory of GBS.

The most common infectious pathogens are:

• Campylobacter - Causes campylobacter enteritis, a disease of the gastrointestinal tract. Symptoms are characterized by high fever, headache, colicky abdominal pain, especially in the right lower abdomen, which may mimic appendicitis. Bloody diarrhea with admixture of pus and mucus is present. Patients have nausea but do not vomit.
• Mycoplasma is a bacterium without a cell wall that causes atypical pneumonia.
• Cytomegalovirus - A virus that does not cause symptoms in healthy people. However, in immunocompromised people, e.g. after organ transplantation, the infection is severe. It presents with fever, enlarged lymph nodes, weakness, fatigue, muscle and joint pain, and inappetence. The most serious symptoms are hepatitis, pneumonia, encephalitis, and infections of the oesophagus, colon and eyes.
• Epstein-Barr virus - The causative agent of infectious mononucleosis. The disease is often confused with strep throat because of its similar symptoms. The virus affects the endocrine glands, spleen, liver, lymph nodes and larynx.
• Haemophilus - The most serious infectious disease is infectious epiglottitis. It also causes sinusitis, otitis media, pneumonia and severe purulent meningitis.

This infection is the stimulus for the production of antibodies. Based on the structural and chemical similarity of the molecules in the envelope of these pathogens to the body's own tissues, antibodies are produced which are directed against the body's own structures.

This is a 'mistaking' of the enemy based on its similarity to one's own. This phenomenon is referred to in immunology as molecular mimicry.

The cause of GBS is based on autoimmune mechanisms of peripheral nerve damage.

In the demyelinating forms, gangliosides of myelin sheaths of nerves are attacked by autoantibodies. In the axonal form, autoantibodies are directed against glycoprotein structures located in the cell membrane of nerve processes called axons.

GBS recurs quite frequently.

Up to 5% of cases recur. This is several times more than in random and sporadic cases. Experts therefore suspect that certain genetic factors are involved in the disease.

These are the genes responsible for the activation of immunity and the subsequent cascade of autoimmune reactions.

In addition to infectious diseases and genetic predisposition, there are other risk factors for the development of GBS:

• previous hepatitis (inflammation of the liver)
• use of drugs such as heroin, suramin and streptokinase
• chronic diseases such as systemic lupus erythematosus and HIV or AIDS infection
• active immunisation, i.e. vaccination against e.g. influenza, rabies, etc.

Symptoms described by Guillain, Barré and Stohl as early as 1916 included:

• muscle weakness
• areflexia - absence of tendon-muscle reflexes
• sensory symptoms such as tingling and burning with slight loss of sensation
• albuminocytological dissociation of cerebrospinal fluid (CSF)

Today, we no longer distinguish different symptoms according to which variant of GBS the patient is affected by. There are several clinical variants, including acute motor axonal neuropathy, acute motor and sensory axonal neuropathy.

The common symptom of all GBS variants is progressive symmetrical paralysis and areflexia over hours to days. The paralysis progresses in an ascending fashion, i.e. from the bottom up, which is very typical for GBS. It is accompanied by muscle pain.

First the legs are affected, then the whole lower limbs. Later, there is an inability to stand and walk on the heels. The next progression is the inability to walk due to weakness of the thigh muscles in particular. Gradually, the paralysis spreads to the upper limbs.

If the disease is left untreated at this stage, it progresses and the patient is unable to sit up, his face becomes flaccid due to paralysis of the facial nerves and muscles, he cannot lift his head, he cannot move his eyes due to involvement of the oculomotor nerves.

In the more severe stage of the disease, swallowing is impaired and the diaphragm, the most important respiratory muscle, is weakened. The patient has difficulty breathing, breathing only in quick, gasping, short breaths - tachypnoea.

Hypoxia occurs, i.e. low oxygen concentration in the blood and tissues. Body cells begin to suffocate.

Respiratory failure due to neuromuscular failure is not uncommon. It requires admission to the intensive care unit with the need for artificial pulmonary ventilation.

At the same time, sensory impairment in the extremities may or may not occur.

Autonomic symptoms develop along with motor and sensory symptoms. They occur in up to 65% of patients admitted to hospital. They can be very severe and worsen the patient's overall prognosis.

In particular, they include the following symptoms:

• orthostatic hypotension (lowering of blood pressure while standing)
• anhidrosis (absence of sweating)
• urinary retention
• gastrointestinal atony (problems with bowel patency)
• iridoplegia (immobility of the pupils)

A variant of GBS, Miller-Fisher syndrome, which accounts for 5% of GBS cases, is characterised by the following symptoms:

• ophthalmoplegia
• ataxia
• areflexia

The disease begins with double vision (diplopia), followed by impaired limb coordination and gait.

In 1981, long-requested diagnostic criteria for GBS were established. These include progressive muscle weakness in more than two limbs, absence of tendon-muscle reflexes in the limbs, and progression that lasts no longer than 4 weeks.

Supportive criteria include mild sensory symptoms, relative symmetry of symptoms, facial palsy, and a cerebrospinal fluid albuminocytology profile.

This is called dissociation. This means that there is an elevated protein concentration in the cerebrospinal fluid but the cellular findings are normal.

The only exception to this criterion is patients with HIV infection, where such a CSF picture is the norm.

Laboratory analysis of cerebrospinal fluid

By performing a lumbar puncture, it is possible to obtain cerebrospinal fluid, which provides valuable information about ongoing reactions in the CNS, e.g. infectious or autoimmune.

When GBS is suspected, this examination is performed primarily for differential diagnostic reasons.

A typical finding in GBS is the picture of a so-called proteinocytological dissociation. This is an increased protein content in the lymph with a low cell count. However, such a finding occurs in only 64 % of patients.

High protein levels during the first three days occur in only half of patients and after the first week in 80% of patients.

Such an increase in protein levels may also be a false positive finding. It may be caused, for example, by the administration of high doses of immunoglobulins in the treatment of GBS.

An excessively high cell count in the lymph is a sign of another diagnosis.

Diseases such as soft palate tumours, lymphoma, cytomegalovirus radiculitis, HIV polyneuropathy or poliomyelitis - an infection caused by a virus - are particularly important in the differential diagnosis.

Electrophysiological examination (EMG)

This is a detailed examination of the conductivity of peripheral nerves. In neurology, it is one of the common methods in the diagnosis of many diseases.

It provides valuable information in the diagnosis of GBS, especially in distinguishing its variants.

However, even this examination does not provide a 100% certain result. Confusion can occur, for example, at a very early stage of clinical symptoms. At that time, the measured nerve conductivities may be quite normal.

Most often, pathology is detected on examination up to two weeks after the onset of symptoms, especially in the affected limbs.

Laboratory tests may show an increased erythrocyte sedimentation rate, abnormal laboratory results of renal and hepatic parameters.

Disturbances of some mineral electrolytes, e.g. hyponatraemia (low sodium levels), are also present.

In Miller-Fisher syndrome, serum IgG antibodies to ganglioside GQ1b are present in most patients.

Anti-GM1 and anti-GD1 (IgG) antibodies are frequently found in the blood of patients with the GBS variant AMAN.

GBS is a relatively acute disease with a dramatic course and the need for hospitalization with possible connection to artificial pulmonary ventilation.

The onset of symptoms takes 4 weeks and the gradual disappearance of all symptoms can take twice as long.

Overall, patients affected by GBS have a good prognosis. Modernisation of treatment and care has improved patient survival, with mortality reduced from 33% to 5-10%.

The biggest advance in the treatment of GBS has been the introduction of positive pressure ventilation.

The vast majority of patients recover from the disease with only mild permanent sequelae within approximately one year. However, some patients suffer irreversible damage and subsequent permanent neurological disability.

Approximately 20% of patients have permanent paralysis of the limbs and muscle atrophy. Sensory neuropathies manifested by unpleasant sensations such as tingling, tingling or numbness are common residual disabilities.

Many patients also report a permanent reduction in performance and chronic fatigue.