Study Notes on Reye Syndrome and Guillain-Barré Syndrome

Reye Syndrome Overview

• Reye syndrome is an acute inflammatory polyneuropathy.

• Typically occurs after an episode of:

  • Gastroenteritis

  • Respiratory tract infection

• Considered an autoimmune condition where:

  • Antibodies lead to an immune attack on the myelin or axons of peripheral nerves.

  • Involves both motor and sensory nerves and can also affect autonomic nerves.

• Target molecules are gangliocytes, composed of lipids and carbohydrates in nerve cell membranes.

• Notable antibodies include:

  • Anti-GM1

  • GD1a

  • GD1b

Mechanism of Reye Syndrome

• Exact mechanism is unclear but may involve molecular mimicry.

• Professor Rick Mitchell discusses the academic success in identifying that:

  • Antibodies generated against specific antigens (possibly from microbes) can cross-react with gangliosides.

• Example:

  • Campylobacter jejuni bacterial capsular lipo-oligosaccharides may generate antibodies that cross-react with myelin leading to:

  • Damage to the myelin, Schwann cells, and axon.

  • Ineffective nerve signal transmission.

Subtypes of Guillain-Barré Syndrome (GBS)

• Multiple subtypes based on:

  • Mechanism of demyelination vs. axon involvement

• Acute Inflammatory Demyelinating Polyneuropathy (AIDP):

  • Most common subtype (80-90% of cases)

  • Characterized by segmental loss of myelin.

  • Often resolves after the immune response is halted.

• Acute Motor Axonal Neuropathy (AMAN):

  • More prevalent in Japan and China.

  • Targets larger motor neurons with minimal myelin loss.

Symptoms of GBS

• Symptoms vary by subtype:

  • AIDP: Both motor and sensory symptoms.

  • AMAN: Primarily motor weakness without sensory loss.

• AIDP clinical features include:

  • Progressive symmetrical weakness (ascending):

  • Begins distally and moves proximally.

  • Typically starts in the legs.

  • Rapid progression over days leading to flaccid paralysis (reduced muscle tone).

  • Maximum severity usually reached within two weeks;

    • Progression beyond four weeks suggests chronic demyelinating process.

  • Following the peak, a plateau phase occurs lasting several weeks, then symptoms may begin to resolve.

• Facial muscles may be involved; this is a leading cause of acute flaccid paralysis in children.

• Common symptoms:

  • Paresthesia in hands and feet, often preceding weakness.

  • Pain mainly in back and legs, especially in children.

  • Respiratory distress:

  • Occurs in 20-30% of patients due to respiratory muscle involvement.

  • Reflexes:

  • Absent or minimal reflexes, particularly affecting ankle and knee.

  • Rare hyperreflexia can occur.

  • Other symptoms may include:

  • Speech slurring

  • Dysphagia (difficulty swallowing)

  • Diplopia (double vision)

  • Dysautonomia (autonomic nervous system involvement) leading to:

    • Sinus tachycardia

    • Hypertension

    • Postural hypotension

Other Subtypes of GBS

• Miller Fisher syndrome:

  • Characterized by:

  • Ophthalmoplegia

  • Areflexia

  • Ataxia

• Bickerstaff's Brainstem Encephalitis:

  • Similar to Miller Fisher but also involves altered consciousness and hyperreflexia.

• Acute Motor and Sensory Axonal Neuropathy (AMSAN):

  • Includes axonal loss of sensory nerves and acute pan-dysautonomia:

  • Symptoms: diarrhea, ileus, vomiting, abdominal pain, urinary retention, heart rate and blood pressure disturbances.

• Pure Sensory GBS:

  • Characterized by acute sensory loss and sensory ataxia.

• Pharyngeal-Cervical-Brachial variant:

  • Features acute arm weakness, swallowing dysfunction, and facial weakness.

Epidemiology of GBS

• 2 out of 3 cases occur within six weeks of an infection.

• Common infectious triggers include:

  • Campylobacter jejuni in up to 39%

  • Cytomegalovirus in up to 22%

  • Epstein Barr virus in up to 13%

  • Mycoplasma pneumoniae in around 5%

• Associated with:

  • COVID-19

  • Zika virus

• Slightly more common in males (ratio 1.78:1).

• Mean age of onset: 40 years.

Diagnostic Studies for GBS

• Nerve conduction studies and electromyography confirm peripheral neuropathy presence.

• Cerebrospinal fluid (CSF) analysis is vital, looking for albuminocytological dissociation:

  • Elevated protein level with normal cell count.

  • Can take time to develop;

  • 1 in 10 cases may never develop this finding.

• CSF analysis also important to rule out other infections.

• Blood tests:

  • Look for specific anti-ganglioside antibodies; a negative result doesn't rule out GBS.

• Routine culture or serology for triggering infection is usually not performed.

• Bedside spirometry is commonly done (typically every six hours) due to rapid progression risk, particularly for respiratory muscle involvement.

• Risks of respiratory failure:

  • Nearly 18-fold with bulbar dysfunction.

  • 9-fold with cough difficulty.

  • Associated with inability to lift head from pillow.

• Tools like the Erasmus GBS Respiratory Insufficiency Score help predict risk based on multiple factors.

Treatment of GBS

• Treatment includes supportive care and disease-modifying medication with a multidisciplinary approach that may include rehabilitation.

• Supportive care actions may involve:

  • Mechanical ventilation

  • Blood pressure and cardiac monitoring, essential in cases with dysautonomia.

  • Managing hypotension with IV fluids; hypertension managed with short-acting agents (e.g., labetalol or nitroprusside).

  • DVT prophylaxis due to prolonged immobility and medication side effects.

• Pain control:

  • Agents like carbamazepine, amitriptyline, or gabapentin may help with neuropathic pain.

  • Heat application can provide relief.

• Rehabilitation recommendation includes passive joint movement from onset; immobilization is not recommended.

• Disease-modifying treatments focus on immunotherapy:

  • Main options:

  • Intravenous immunoglobulins

  • Plasma exchange (less common, requires central line).

  • Corticosteroids have not shown benefits and may worsen outcomes.