Guillian-Barré syndrome

Definition

Acute onset of peripheral neuropathy with progressive muscle weakness (more severe proximally) with areflexia, reaches maximum over 3 days to 3 weeks

Diagnosis

When to suspect GBS

Rapidly progressive bilateral limb weakness and/or sensory deficits

Hypo/areflexia

Facial or bulbar palsy

Ophthalmoplegia and ataxia

How to diagnose GBS

Check diagnostic criteria

Exclude other causes

Consider

Routine laboratory tests
CSF examination
Electrophysiological studies

Acute care

When to admit to ICU (one or more)

Rapid progression of weakness

Severe autonomic or swallowing dysfunction

Evolving respiratory distress

EGRIS >4

When to start treatment (one or more)

Inability to walk >10m independently

Rapid progression of weakness

Severe autonomic or swallowing dysfunction

Respiratory insufficiency

Treatment options

Intravenous immunoglobulin (0.4 g/kg daily for 5 days)

Plasma exchange (200–250 ml/kg for 5 sessions)

Monitoring

Regularly assess

Muscle strength
Respiratory function
Swallowing function
Autonomic function

Blood pressure
Heart rate/rhythm
Bladder/bowel control

Early complications

Choking

Cardiac arrhythmias

Infections

Deep vein thrombosis

Pain

Delirium

Depression

Urinary retention

Constipation

Corneal ulceration

Dietary deficiency

Hyponatraemia

Pressure ulcers

Compression neuropathy

Limb contractures

Clinical progression

Treatment-related fluctuation: repeat same treatment

No initial response or incomplete recovery: No evidence for repeating treatment

Long-term care

Predicting outcome

Calculate mEGOS on admission

Recovery can continue >3 years after onset

Recurrence is rare (2–5%)

Rehabilitation

Start rehabilitation programme early

Manage long-term complaints: fatigue, pain and psychological distress

Contact GBS patient organizations

Clinical variants

Graphic representation of the pattern of symptoms typically observed in the different clinical variants of Guillain–Barré syndrome (GBS).

Symptoms can be purely motor, purely sensory (rare) or a combination of motor and sensory.
Miller Fisher syndrome

Ataxia

Bickerstaff brainstem encephalitis

Decreased consciousness
Ataxia

Symptoms can be localized to specific regions of the body, and the pattern of symptoms differs between variants of GBS.

Although bilateral facial palsy with paraesthesias, the pure sensory variant and Miller Fisher syndrome are included in the GBS spectrum, they do not fulfil the diagnostic criteria for GBS.

Diagnostic criteria by National Institute of Neurological Disorders and Stroke (NINDS)

Features required for diagnosis

Progressive bilateral weakness of arms and legs (initially only legs may be involved)

Absent or decreased tendon reflexes in affected limbs (at some point in clinical course)

Features that strongly support diagnosis

Progressive phase lasts from days to 4 weeks (usually <2 weeks)

Relative symmetry of symptoms and signs

Relatively mild sensory symptoms and signs (absent in pure motor variant)

Cranial nerve involvement, especially bilateral facial palsy

Autonomic dysfunction

Muscular or radicular back or limb pain

Increased protein level in cerebrospinal fluid (CSF); normal protein levels do not rule out the diagnosis

Electrodiagnostic features of motor or sensorimotor neuropathy (normal electrophysiology in the early stages does not rule out the diagnosis)

Features that cast doubt on diagnosis

Increased numbers of mononuclear or polymorphonuclear cells in CSF (>50 × 106/l)

Marked, persistent asymmetry of weakness

Bladder or bowel dysfunction at onset or persistent during disease course

Severe respiratory dysfunction with limited limb weakness at onset

Sensory signs with limited weakness at onset

Fever at onset

Nadir <24 h

Sharp sensory level indicating spinal cord injury

Hyper-reflexia or clonus

Extensor plantar responses

Abdominal pain

Slow progression with limited weakness without respiratory involvement

Continued progression for >4 weeks after start of symptoms

Alteration of consciousness (except in Bickerstaff brainstem encephalitis)

Mechanism

Infections with pathogens, such as Campylobacter jejuni, can trigger humoral immune and autoimmune responses that result in nerve dysfunction and the symptoms of GBS.

Infection with Campylobactoer jejuni → Lipo-oligosaccharides on the C. jejuni outer membrane may elicit the production of antibodies that cross react with gangliosides, such as GM1 and GD1a on peripheral nerves.

Location of antigen determines the subtype of GBS

Acute motor axonal neuropathy (AMAN)

Antigens are located at or near the node of Ranvier.
The anti-GM1 and anti-GD1a antibodies bind to the nodal axolemma → complement activation → membrane attack complex formation → disappearance of voltage-gated sodium channels → This damage can lead to detachment of paranodal myelin → nerve conduction failure.
Macrophages then invade from the nodes into the periaxonal space, scavenging the injured axons.

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)

Antigens are located on the myelin sheath.
The antibodies can activate complement → formation of the membrane attack complex on the outer surface of Schwann cells → initiation of vesicular degeneration and invasion of myelin by macrophages.

Subtypes

Type	Symptoms	Pathology	Antibodies	NCS Findings
AIDP	Most common variant (85% cases); primarily motor damage; max of 4 wk of progression	Macrophages invade intact myelin sheaths and denude the axons	Various*	Demyelination polyneuropathy
AMAN	Motor only with early and severe respiratory involvement; primary axonal degeneration; often affects children/young adults; up to 75% positive Campylobacter jejuni serology	Macrophages invade the nodes of Ranvier where they insert between the axon and the surrounding Schwann-cell axolemma, leaving the myelin sheath intact	GM1a, GM1b, GD1a	Axonal polyneuropathy Sensory action potential normal
AMSAN	Motor and sensory involvement with severe course of respiratory and bulbar involvement; primary axonal degeneration with poor prognosis	Similar to AMAN but also involving ventral and dorsal roots	GD1a, GalNAc-GD1a*	Axonal polyneuropathy Sensory action potential reduced or absent
Miller Fisher Syndrome	Ophthalmoplegia, sensory ataxia, areflexia; 5% of all cases;	Abnormality in sensory conduction although underlying pathology is not clear	90% positive for anti-GQ1b antibodies	Normal in most patients Discrete changes in sensory conduction or H reflex may be present
Acute pandysautonomic neuropathy	Most rare form; may be accompanied by encephalopathy	Widespread sympathetic & parasympathetic failure	-

Subtype	Antibody (ganglioside target)
AIDP	UNKNOWN
AMSAN	GM1, GM1b, GD1a
AMAN	GM1, GM1b, GD1a, GalNAc-GD1a
MFS (Miller Fisher syndrome)	GQ1b, GT1a
Acute sensitive neuronopathy	GD1b
Orofacial variant	GT1a
Overlap MFS/GBS	GQ1b, GM1, GM1b, GD1a, GalNAc-GD1a

Imaging

No characteristic finding; however, diffuse enhancement of cauda equina and nerve roots occurs in up to 95% of cases.

Thought to be due to disruption of the blood-nerve barrier from inflammation.

Conspicuous nerve root enhancement correlates with pain, GBS disability grade, and duration of recovery.

Treatment

Immunoglobulins may be helpful.

In severe cases, early plasmapheresis hastens the recovery and reduces the residual deficit.

Its role in mild cases is uncertain.

Steroids are not helpful.

Mechanical ventilation and measures to prevent aspiration are used as appropriate.

In cases of facial diplegia, the eyes must be protected from exposure (neuroparalytic) keratitis.

Outcome

Recovery may not be complete for several months.

35% of untreated patients have residual weakness and atrophy.

Recurrence of GBS after achieving maximal recovery occurs in ≈ 2%.

Differential diagnosis

Inflammation or infection of the brainstem (for example, sarcoidosis, Sjögren syndrome, neuromyelitis optica or myelin oligodendrocyte glycoprotein antibody-associated disorder)a
Inflammation or infection of the spinal cord (for example, sarcoidosis, Sjögren syndrome or acute transverse myelitis)
Malignancy (for example, leptomeningeal metastases or neurolymphomatosis)
Compression of brainstem or spinal cord
Brainstem stroke
Vitamin deficiency (for example, Wernicke encephalopathya, caused by deficiency of vitamin B1, or subacute combined degeneration of the spinal cord, caused by deficiency of vitamin B12)

Anterior horn cells

Acute flaccid myelitis (for example, as a result of polio, enterovirus D68 or A71, West Nile virus, Japanese encephalitis virus or rabies virus)

Nerve roots

Infection (for example, Lyme disease, cytomegalovirus, HIV, Epstein–Barr virus or varicella zoster virus)
Compression
Leptomeningeal malignancy

Peripheral nerves

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
Metabolic or electrolyte disorders (for example, hypoglycaemia, hypothyroidism, porphyria or copper deficiency)
Vitamin deficiency (for example, deficiency of vitamins B1 (also known as beriberi), B12 or E)
Toxins (for example, drugs, alcohol, vitamin B6, lead, thallium, arsenic, organophosphate, ethylene glycol, diethylene glycol, methanol or N-hexane)
Critical illness polyneuropathy
Neuralgic amyotrophy
Vasculitis
Infection (for example, diphtheria or HIV)

Neuromuscular junction

Myasthenia gravis
Lambert–Eaton myasthenic syndrome
Neurotoxins (for example, botulism, tetanus, tick paralysis or snakebite envenomation)
Organophosphate intoxication

Muscles

Metabolic or electrolyte disorders (for example, hypokalaemia, thyrotoxic hypokalaemic periodic paralysis, hypomagnesaemia or hypophosphataemia)
Inflammatory myositis
Acute rhabdomyolysis
Drug-induced toxic myopathy (for example, induced by colchicine, chloroquine, emetine or statins)
Mitochondrial disease

Other

Conversion or functional disorder

Bickerstaff brainstem encephalitis.

Reference

Leonhard 2019

Berg 2014