Guillain-Barre Syndrome (Acute Inflammatory Demyelinating Polyneuropathy)
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1-2/100,000/yr
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All age groups
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Peaks in young adults and the elderly
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Infection
evokes and immune response which cross-reacts with peripheral nerve components
because of shared epitope
Can be directed against myelin or axon
In the major (or classic) form AIDP it is directed against myelin
o Both a cellular and hummoral response
o T-cells infiltrate followed by macrophages, complement and antibodies
Axonal forms (AMAN and AMSAN) are directed against axonal antigens
o Infection with C.jejuni can result in anti-ganglioside antibodies (inc. GM1, GD1a)
Miller fisher Syndrome
o Anti-ganglioside antibodies (GQ1b) a component of oculomotoe nerve myelin occur in 85-90%
Campylobacter jejuni strongly associated
o 26% of cases associated with this infection
o GBS in this context has a worse prognosis
o GBS develops in 0.03% of patients who get infection
HIV
EBV, CMV
Mycoplasma
VZV, HSV, hepatitis,
Haemophilus and E.coli
Vaccinations weak association
o Specific outbreak after swine flu vaccination in 1976
Systemic illness e.g. SLE
Progressive,
fairly symmetric muscle weakness accompanied by absent or depressed reflexes
Weakness
o Onset of weakness usually begins in proximal legs. Onset in arms and facial muscles in 10%
o Severe respiratory muscle weaknes in 10-30%
o Facial weakness in > 50%
o Oropharyngeal weakness in ~50%
o Occulomotor weakness in 15%
Sensory changes in 80%
o Usually paresthesias in hands and feet
o Severe low back pain may occur
Autonomic dysfunction -70%
o Tachycardia (most common)
o Urinary retention
o BP instability
o Bradycardia
o Ileus
Respiratory compromise ~30%
AIDP (Acute inflammatory demyelinating polyneuropathy)
o Main form, classical GBS
o Features above relate to this form
Miller Fisher Syndrome (MFS) (5% in west, up to 25% in Japan)
o Opthalmoplegia, Ataxia and areflexia
o 25% develop limb weakness
AMAN - Acute motor axonal neuropathy
o (5% combined with AMSAN, greater incidence in Asia)
o 30-47% in asia
o Only motor involvement, tendon reflexes may be preserved
o NCS shows axonal pattern of involvement
o Worse prognosis due to axonal involvement
o DDX: CIPN, Vasculitis, Toxic (arsenic), Botulism, HKPP, poliomyelitis
AMSAN - Acute motor and sensory axonal neuropathy
o Same as AMAN however more severe and involving sensory axons as well.
o DDx: Porphyria
Progressive weakness of more than one limb
Distal areflexia with proximal areflexia or hyporeflexia
Progression for up to 4 weeks
Relatively symmetric deficits
Mild sensory involvement
Cranial nerve (esp VII) involvement
Recovery beginning within 4 weeks after progression stops
Autonomic dysfunction
No fever at onset
Increased CSF protein after one week
CSF WCC <10
Nerve conduction slowing or block by several weeks
Markedly asymmetric weakness
Bowel or bladder dysfunction (at onset or persistent)
CSF WCC >50 or Neutrophils >0
Well demarcated sensory level
Isolated sensory involvement
Another polyneuropathy that explains clinical picture
During first few days NCS may be normal
Delayed, absent or impersistent F and H responses may be the first changes indicate proximal demyelination
The full criteria (below) are present in 50% by 2 weeks, 85% by 3 weeks and 90% of patients overall
10% of patients will never the full criteria
Sensory changes are typically not seen early
o May be affected later, often with sural sparing
For definite diagnosis -demonstrate at
least 3 of the following in motor nerves
1. Prolonged distal latencies (2 or more nerves, not at entrapment sites)
a. DL >115% ULN (If CMAP amplitude in normal range)
b. DL >125% ULN (if CMAP amplitude in low, below LLN)
2. CV slowing (2 or more nerves, not at entrapment sites)
3. Prolonged late response: F or H response (One or more nerves)
a. >125% ULN
4. Conduction block/temporal dispersion (one or more nerves)
a. Unequivicol conduction block: Prox/distal CMAP area ratio <0.5
b. Possible conduction block: Prox/distal CMAP area ratio <0.7
c. Temporal dispersion: Prox/distal CMAP duration ratio >1.15
AMAN (Acute motor axonal neuropathy) Predominantly axonal, pure motor
AMSAN (Acute motor sensory axonal neuropathy) Predominantly axonal, motor and early sensory involvement (N.B. DDx Porphyria)
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Elevated protein with normal WCC (albuminocytologic
dissociation) 80-90% at one week after onset
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AMAN
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Anti GM1, GM1a, Ga1NAc, GD1a, GM1b
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At least one of these is present in 83% of cases
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MFS/BBE
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AntiGq1b ~90%
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AIDP
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No consistent antibody associations
Supportive
care
o Respiratory support
o Predictors include FVC <20ml/Kg or <60% predicted
o A risk factor score was trialled with clinical features such as inability to cough etc.
o Avoid succinylcholine
IV Immunoglobulin (Intragam)
o 400mg/kg/day for 5 days
o Similar efficacy to plasmaphoesis
o No additive benefit with plasmapheresis
Plasma exchange/Plasmapheresis
o Proven effective
o Improved median time to recover walking and time to onset of motor recovery
- Time to walk unaided improved by 32 days
- Time on ventilator improved by 12 days
o Plasma protocol 200-250ml/kg, 4-6 exchanges of 2-4 L over 5-14 days
Corticosteroids NOT BENEFICIAL may be harmful
Symptoms
usu cease to progress by 4 weeks
Plateau for 2-4 weeks, then recovery begins
At 1 year:
o 70-75% recover completely
o 25% are left with mild neurological deficits
o 5% die usu. of respiratory failure
By 2 years a further ~10% (i.e. 85% of all patients) achieve complete recovery.
5% recurrence rate.
Prognosis is poorer if
o there is evidence of preceding Campylobacter jejuni infection
o Advanced age
o Need for respiratory support
o Rapid onset of symptoms