Guillain-Barré syndome Flashcards
Which parts of the body are considered to be part of the central nervous system (CNS)?
- Brain
- Myelum
- Optic nerve
Which parts of the body are considered to be part of the peripheral nervous system (PNS)? (4)
- Nerve roots
- Dorsal root ganglia
- Peripheral nerves
- Cranial nerves (with exception of N. II)
Which three layers do peripheral nerves have (outside to inside)?
- Epineurium, connective tissue encapsulating the whole nerve
- Fasicles of nerve fibres, encapsulated in perineurium
- Endoneurium -> individual nerve fibres
What are peripheral nerve fibres surrounded by? Is this also true for unmyelinated neurons?
Schwann cells, this is true for all neurons in the PNS
What are the myelinating cells of the PNS, and of the CNS? How many axons can each of these cell types myelinate?
PNS = Schwann cells, myelinate 1 axon
CNS = oligodendrocytes, can myelinate >1 axon
What are the gaps between myelinated patches of axons called? What is their function?
Patches of Ranvier, necessary for fast transmission of electrical impulses
Does the PNS have a blood-brain barrier?
Yes
What does the PNS blood-brain carrier consist of? (2)
- Tight junctions between endothelial cells of the blood vessels
- Regulation of endothelium by pericytes
True or false: the PNS blood-brain barrier is tight across the PNS
False; it is leaky at nerve roots, ganglions and nerve terminals
Where can immune cells and immunoglobulins access the PNS?
Places where the PNS blood-brain barrier is leaky, such as nerve roots and nerve terminals
Does the PNS present antigens?
Neurons don’t present antigens, but MHCII is inducible on Schwann cells
Are there immune cells within the PNS in physiological circumstances?
Yes, endoneurial macrophages
What is the function of endoneurial macrophages?
They are needed for Wallerian degeneration -> important for nerve generation after severing of nerves
Why are peripheral nerves especially vulnerable cells? (2)
- Largest cells in the human body
- Require intact cell surface for normal electrophysiology
Which serum marker is often elevated in immune-mediated neuropathies?
M-protein/paraprotein -> antibodies against antigenic sites on nerves
True or false: GBS is the most frequent cause of acute neuromuscular paralysis in all countries
False; GBS is the most common cause of acute neuromuscular paralysis in countries without polio
What is the incidence of GBS?
1-2/100.000 persons/year
What is the lifetime risk of GBS?
1/1000
GBS is more common at [lower/higher] age
Higher age
What is the male:female ratio of GBS patients? What is remarkable about this?
M:F = 3:2
Most auto-immune diseases are more common in women, whilst GBS is more common in men
What are the symptoms of GBS? (4)
- Muscle paralysis
- Sensory deficits
- Autonomic dysfunction
- Areflexia
How can muscle paralysis in GBS manifest itself? Which of these presentations is life-threatening?
- Inability to move limbs, eyes, face
- Inability to speak/swallow
- Respiratory insufficiency (=life-threatening)
How can sensory deficits of GBS manifest? (3)
- Pain/tingling
- Numbness, absent sence of pain/touch
- Absent position sense (=ataxia)
How can autonomic dysfunction in GBS manifest itself? (2)
- Tension fluctuations
- Cardiac arrythmia
How is GBS diagnosed?
Mostly based on clinical features, can be supplemented by additional examinations
Which clinial features are enough to diagnose GBS? (3)
- Rapidly progressive (<4) weeks
- Symmetrical paralysis of arms & legs
- Reduced/absent reflexes
Which additional examinations can be performed to support a GBS diagnosis? (3) What will be their outcomes?
- Blood = no abnormalities
- CSF = no cells, increased protein level
- Electrophysiology = demyelination & axonal degeneration
Why is CSF used in the diagnostics of GBS (which is a PNS disease)?
To rule out CNS infection
What is the hypothesis for the cause of elevated protein levels in CSF in GBS? (2)
- Damage to nerves, causing them to leak protein
- Damage to the blood-brain barrier, causing leakage of protein
Which other causes of paralysis need to be ruled out to confirm GBS? (3)
- Nitrous oxide poisoning
- Vitamin deficiency
- Infections
What is the sequence of events/phases of GBS?
- Infection -> antibodies produced
- Infection cleared -> antibodies decline, but do cause damage to nerves (cross-reactive)
- Serum antibodies to gangliosides cause progression of GBS -> start of nerve syptoms
- Antibodies will get cleared -> plateau phase of nerve sypmtoms
- Recovery phase and possibly lasting disability
Which part of the body is affected by classical GBS?
Whole body
What is Miller-Fisher syndrome?
A subtype of GBS that consists of a triad of:
1. Ataxia
2. Opthalmoplegia
3. Areflexia
Which phenomenon explains GBS symptomatology?
Demyelination of PNS nerves
What is characteristic myelin damage seen in GBS? (4)
- Myelin sheath surrounded by macrophages, attack myelin sheath
- Macrophages within the myelin sheath, causing direct axonal damage
- Complement activated on Schwann cell surfaces
- Antibodies to glycolipids present in ~50% of cases
Which group of glycolipids is mostly attacked in GBS?
Gangliosides -> sialic acid containing glycolipids
Why do anti-ganglioside antibodies cause neurological symptoms?
Gangliosides are especially abundant on neuronal cell membranes & myelin
What is most often the target of anti-ganglioside antibodies in GBS?
GM1
True or false: the type of ganglioside attacked does not affect symptomatology, as they are all present in the PNS
False; some gangliosides are more abundant in certain parts of the PNS -> antibodies against these will cause symptoms specific to these sites
Which type of gangliosides are more present on oculomotor nerves? Why is this relevant?
Disialic acids -> antibodies against these cause Miller-Fisher syndrome (exclusive to oculomotor muscles)
Which histological classifications of GBS can be identified? (4)
- Demyelination -> acute inflammatory demyelinating polyneuropathy (AIDP)
- Axonal degeneration (AMAN)
- Miller-Fisher syndrome
- AMSAN
What are the symptoms in case of demyelination (AIDP)?
Motor and sensory neurons attacked -> both paralysis & loss of sensory function
What are the syptoms in case of axonal degeneration (AMAN)?
Only axons attacked -> only motor symptoms
What are disease-specific therapies used in GBS? (2)
- Plasma exchange/plasmapheresis
- IVIG = preferred
What is supportive therapy used in GBS? (3)
- Artificial respiration
- Prevention & treatment of complications
- Physiotherapy & rehabilitation
Which features set GBS apart from other auto-immune diseases? (5)
- No predominance in females
- No association with other auto-immune diseases
- No relapsing-remitting or chronic disease cause
- No association with specific HLA haplotypes
- No improvement after corticosteroids
What is the most common type of preceding infection in GBS?
Gastro-intestinal or respiratory infection
How many % of GBS patients has evidence for recent infection?
50-60%
How can electrophysiology be used to distinguish between axonal and demyelinating GBS?
Demeylinating = reduced velocity of conduction
Axonal = reduced amplitude/no connection
Which 6 infections have been proven to be associated with GBS in large cohorts?
- C. jejuni
- Mycoplasma pneumoniae
- Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
- Hepatitis E virus (HEV)
- Zikavirus (ZIKV)
What are the characteristics of post-campylobacter GBS when it comes to:
1. Clinical/EMG phenotype
2. Outcome
3. Anti-ganglioside antibodies
- Pure motor or Miller-Fisher syndrome -> axonal damage
- Worse outcome
- Anti-GM1 antibodies (most common)
What are the characteristics of post-mycoplasma GBS when it comes to:
1. Clinical/EMG phenotype
2. Outcome
3. Anti-ganglioside antibodies
- Sensorimotor GBS or MFS with both axonal damage & demyelination
- Good outcome
- Gal-C antibodies
What are the characteristics of post-CMV GBS when it comes to:
1. Clinical/EMG phenotype
2. Outcome
3. Anti-ganglioside antibodies
- Sensorimotor GBS -> demyelinating
- Good outcome
- Antibodies unkown
What are the characteristics of post-EBV GBS when it comes to:
1. Clinical/EMG phenotype
2. Outcome
3. Anti-ganglioside antibodies
- Sensorimotor GBS -> demyelinating
- Good outcome
- Antibodies unknown
What are the characteristics of post-HEV GBS when it comes to:
1. Clinical/EMG phenotype
2. Outcome
3. Anti-ganglioside antibodies
- Sensorimotor GBS -> demyelinating
- Worse outcome
- Antibodies unkown
What are the characteristics of post-ZIKV GBS when it comes to:
1. Clinical/EMG phenotype
2. Outcome
3. Anti-ganglioside antibodies
- Sensorimotor GBS -> demyelinating
- Worse outcome
- Antibodies unkown
What are possible reasons why not everyone infected with C. jejuni gets GBS? (3)
- Some strains of C. jejuni have more GM1-mimicking motifs on their membrane than others
- Differences in ganglioside presentation between humans
- Differences in severity of immune response between humans
What is the IGOS study?
International GBS Outcome Study -> largest observational cohort of GBS
Why is an international cohort needed to study GBS?
Because it is a relatively raredisease
What was the most common preceding infection in GBS in the IGOS study?
C. jejuni
True or false: GBS-patients always have one pre-GBS infection
False; there are also patients who have >1 preceding infection
True or false: in the majority of GBS-cases, the preceding infection is known
False; ~59% has no previous infection found
What could be triggers for GBS in case a previous infection cannot be established? (4)
- Infections not tested for
- Surgery
- Use of certain drugs
- Vaccines
On basis of what percentage did the IGOS study determine that C. jejuni GBS has the worst outcome?
Based on the % of patients able to walk after 6 months -> this outcome is worst for C. jejuni
Which epidemic has been associated with increased incidence of GBS?
Zikavirus
Was there an increase of GBS during the SARS-CoV-2 pandemic? What important factor does have to be taken into consideration when interpreting this data
There was no peak, but social distancing also reduced the amounts of infections with other pathogens that could cause GBS -> this could hide some cases of GBS caused by SARS-CoV-2
The Astra-Zeneca SARS-CoV-2 vaccine somewhat increased risk of GBS. Still, it can be considered protective against GBS. Why?
The chance of the vaccine causing GBS was smaller than COVID-infection -> protection against COVID-infection = risk-reduction
