Guillain-Barre syndrome

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy (AIDP) that primarily affects the peripheral nervous system’s Schwann cells. It is a relatively rare condition, with an incidence of approximately 2 in 100,000 every year in the UK. This number increases with age and is more prevalent in men than women. Despite its rareness, it is important to be aware of as it can potentially be fatal.

Pathophysiology

GBS occurs due to an immune-mediated attack on the myelin sheath in the peripheral nervous system (i.e. Schwann cells). It attacks both motor and sensory nerves. Sometimes the axon itself is attacked.

The mechanism behind this immune-mediated response is believed to be molecular mimicry. This when a foreign antigen (such as that from bacteria or viruses) has a similar structure to self-antigens. Our immune system produces antibodies against the foreign antigen, but due to the structural similarities these antibodies also attack antigens in the peripheral nerve tissue → inflammation, demyelination, axonal damage. Axonal damage and demyelination leads lack of insulation around the nerves which impairs electrical impulse propogation. This leads to conduction blocks in the PNS → flaccid paralysis, sensory defects.

The reason for this association is because most cases of GBS are preceded by an identifiable infection (in the previous 6 weeks). Most commonly it is an URTO or gastroenteritis. The antigens that the immune system are glycolipids known as gangliosides. These gangliosides are found on the cell membrane of neurons. The most commonly implicated gangliosides are GM1, GM1b, GD1a, GD1b, GalNac-GD1a.

Once the immune reaction stops, repair and re-myelination begin, which correlate with a quick and complete recovery from the flaccid paralysis and sensory defects of GBS (in most cases).

🦠 The pathogens most commonly involved are:

• ⭐️ Campylobacter jejuni - campylobacter enteritis is the most common disease associated associated with GBS
• CMV
• EBV

• SARS-CoV-2

Mycoplasma pneumoniae

• Hepatitis E
• HIV
• Zika virus

💡 Immunisations have been proposed to trigger GBS, but this remains controversial. In the US, GBS is listed as a 'vaccination injury' for the seasonal flu vaccine.

🔢 Classification

We can classify GBS by the symptoms present and the types of nerves that are affected:

1. Acute inflammatory demyelinating polyneuropathy (AIDP) - the most common subtype (95% of cases). It is characterised by widespread demyelination of both motor and sensory nerves.
2. Acute motor and sensory axonal neuropathy (AMSAN) - this is characterised by axonal degeneration (as opposed to demyelination) of both motor and sensory nerves.
3. Acute motor axonal neuropathy (AMAN) similar to AMSAN in that it is also the axon that is targeted and not the myelin sheath. However, this time it is solely the motor axons that are affected.
4. Miller-Fisher syndrome (MFS) - affects the cranial nerves. It is characterised by a triad of ophthalmoplegia, ataxia and areflexia. Associated with the GQ1b ganglioside.
5. Bickerstaff’s brainstem encephalitis (BBE) - similar to MFS but has the additional features of altered consciousness and Babinski sign (extensor plantar reflex)
6. Pharyngeal-cervical-brachial - leads to swallowing dysfunction, facial weakness, and acute arm weakness. Associated with anti-GT1a antibodies.
7. Acute pandysautonomia - patients experience symptoms relating to autonomic dysfunction such as diarrhoea, vomiting, dizziness, abdominal pain, ileus, orthostatic hypotension and urinary retention, bilateral tonic pupils, fluctuating heart rate, decreased sweating, salivation, and lacrimation.

⚠️ Risk factors

• Recent infection
• Seasonal influenza vaccination
• Hodgkin’s lymphoma
• Male sex

😷 Presentation

The presentation of GBS varies significantly, from mild muscle weakness to significant quadriplegia and respiratory failure. The signs and symptoms reflect which nerves have been injured.

The typical presentation of GBS involves sensorimotor deficits:

• Patients commonly have a history of recent infection (such as gastroenteritis).
• Early on patients may experience back and limb pain, both nociceptive pain (pain due to tissue damage or inflammation) and neuropathic (pain due to damage to the nervous system itself). In 1/3rd of cases, pain persists more than 1 year.
• Limbs:
• Progressive ascending flaccid paresis or paralysis
• Paraesthesia - in a stocking-glove distribution.
• Hyporeflexia or areflexia - beginning in the lower limbs and ascending.
• Respiratory muscles: - respiratory failure.
• Cranial nerves:
• Facial diplegia - due to bilateral paralysis of CN VII (facial nerve). CN VII is the most common nerve to be affected in GBS.
• Bulbar palsy - a lower motor neuron palsy caused by bilateral damage or injury of the nerve nuclei of cranial nerves IX, X, XI, and XII. Clinical features include dysphagia, drooling, anarthria, fasciculations of the tongue, and loss of the gag reflex
• Ophthalmoplegia - paralysis of the extra-ocular muscles.
• Autonomic nerves:
• Cardiac arrhythmias
• Labile blood pressure (blood pressure that fluctuates a lot) - with wide variations (≥85 mmHg).
• Urinary retention
• Intestinal dysfunction - such as diarrhoea, or ileus.

💡 Recovery can take months to years. Patients can continue regaining function five years after the acute illness. Most patients eventually make either a full recovery or are left with minor symptoms. Some are left with significant disability. Mortality is around 5%, mainly due to respiratory or cardiovascular complications.

🔍 Investigations

⭐️ Diagnosis of GBS is a clinical diagnosis based on pattern recognition, so taking a full history & neurological examination is essential.

Investigations to consider include:

• Lumbar puncture/CSF analysis - elevated CSF protein with normal white blood cell count (this is known as albuminocytologic dissociation).
• Nerve conduction studies & electromyograpy (EMG) - may show evidence of demyelinating polyneuropathy, such as decreased motor nerve conduction velocity, prolonged distal motor latency, and increased F wave latency (responses when muscles are stimulated).
• Cardiac monitoring - for autonomic instability.
• LFT's - for an unknown reason, AST and ALT may be elevated in the first few days.
• Pulmonary function tests (PFTs) - may show reduced vital capacity
• Serological tests - anti-ganglioside antibodies.

🧰 Management

🚨 Complications

[MILLER FISHER SYNDROME]