GBS Flashcards
Definition
Acute inflammatory demyelinating polyneuropathy
Classical features
Rapidly ascending symmetrical paralysis and sensory deficits
Starts from lower extremities and proximal muscles
Progressive weakness and areflexia over days to weeks (usually around 4 weeks to maximal weakness)
Paraesthesias before motor symptoms
areflexia or hyporeflexia
Bilateral facial weakness
Bulbar weakness (dysarthia, dysphagia)
Respiratory weakness (30% ventilation)
Severe pain (90%) - starts in back and legs
Autonomic dysfunction (failure, arrthymias, liable BP, bowel and bladder, orthostatic hypotension)
Pupillary abnormalities (diplopia)
CVS instability
LMN signs - decreased tone, distally weak power, absent reflexes, absent clonus, plantar response absent or flexor, flaccid paralysis
Pathogenesis of AIDP
Virus or bacteria of antecedent infection have antigens that look similar to the lipid in the myelin sheath. T-cells mistakenly identify myelin epitopes as foreign molecular mimicry. Auto-antigens trigger immune response. T helper cells are activated, which activate B cells and macrophages. B cells make antibodies that mark auto antigens. Macrophage mediated demyelination of peripheral neurons segmentally. Early on remyelination by schwaan cells occurs but later on irreversible - acute polyneuropathy.
Immune reactions directed against epitopes in schwaan cell surface membranes or myelin cause AIDP. Pathology is multifocal inflammatory demyelination starting at the nerve roots. The earliest changes are seen at the nodes of ranvier. Both the cellular and humoral immune responses are involved. Invasion by activated T cells followed by macrophage mediated demyelination with complement and immunoglobulin deposition on myelin and schwaan cells.
Pathogenesis of AMAN
In the acute motor axonal neuropathy (AMAN) form of GBS, the infecting organisms probably share homologous epitopes to a component of the peripheral nerves (molecular mimicry) and, therefore, the immune responses cross-react with the nerves causing axonal degeneration; the target molecules in AMAN are likely to be gangliosides GM1, GM1b, GD1a and GalNAc-GD1a expressed on the motor axolemma.
Damage mediated by IgG antibodies and compliment against the axolemma gangliosides
Bacteria contain antigens similar to the gangliosides portion of the axolemma of the neurons. Immune response against the infection/virus produce antibodies that cross-react with gangliosides in the axons of neurons.
General pathogenesis for GBS
Bacteria and viruses have antigens on their surface that look similar to the lipid in the myelin sheath. Immune cells mistakenly attack and destroy the myelin sheath (molecular mimicry). Auto antigens on myelin get picked up by the antigen presenting cell (like dendritic cells), which present to helper T cells. Helper T cells produce cytokines, which activate B cells and macrophages. B cells make antibodies that mark the auto antigens and macrophages use antibody markers to bind to and strip the myelin sheath off the peripheral neurons. demyelination happens in patches along the length of the axon (segmental demyelination). early on schwaan cells do remyelination but over time the damage is irreversible.
Risk factors for GBS
Preceding viral illness (2/3rd history of gastroenteritis or influenza-like illness weeks before onset) - EBV
Preceding bacterial infection - campylobacteria jejuni
Preceding mosquito borne virus (zika virus)
Flu vaccine
Hep E infection
Possible mechanisms for GBS
TNF pro-inflammatory cytokine - levels correlated with clinical severity but may be neuroprotective/anti-inflammatory
Interleukin 12- pro-inflammatory cytokine - increased in AIDP acute phase, decreased after IVIG, IVIG may down modulate IL-12 receptor dependent pathway
Diagnosis
NCS - AIDP patchy demyelination, slowed motor nerve conduction velocities, prolong distal and F wave latencies and dispersed response on needle, conduction block.
Earliest sign - absent or prolonged F waves on NCS
May take 3-4 weeks for fibrillation to develop on EMG and studies may be normal
Lumbar puncture - CSF elevated protein, normal cell count
Spirometry - reduced vital capacity test (FVC)
Antiganglioside antibodies - Miller fisher syndrome antibodies in 85-90% - useful when clinical diagnosis unclear after clinical examination
MRI to exclude acute cord lesions
Variants of GBS
Acute motor axonal neuropathy (AMAN) - like normal GBS but axonal involvement on NCS, motor symptoms only. Specific antibodies (GM1a, GM1b, GD1a)
Miller fisher syndrome (MFS) - abnormal muscle coordination, paralysis of eye muscles, areflexia, generalised muscle weakness and respiratory failure. Specific antibodies (GQ1b, GT1a) - main difference is weakness begins in the head/eyes
Bickerstaff’s encephalitis - rare post infection extends down brainstem - drowsy/comatose
Pharyngeal-cervical-brachial variant - rapidly progressive oropharyngeal and cervicobrachial weakness, areflexia in upper limbs
Paraparetic variant - rare, leg weakness and areflexia without involvement of arms, cranial nerves and respiratory muscles. lower back pain, bum, leg pain and then flaccid symmetric limb weakness without sensory disturbance. Axonal neuropathy restricted to lower limbs.
Treatment
Plasma exchange (machine removes blood from vein and filters harmful antibodies that are attacking nerves and then returns blood - plasma separated from blood using membrane filtration - labour intensive and high skill) - contraindication IgA deficiency or renal failure complications - infection, BP instability, cardiac arrythmias, pulmonary embolus, pneumonia
IVIG - donated blood that contains healthy antibodies to stop harmful antibodies, peripheral infusion (easier to administer) - risk of transmitting infection/anaphylaxis.
Respiratory support (1/3rd) - arrhythmias, NG feeding, treat and prevent secondary complications (pain, infections)
Supportive treatment - monitor pulse and BP until off ventilation, DVT: subcutaneous heparin or anozaparin with support stocking until able to walk
Intubation/ventilation - early when bulbar dysfunction/high risk for aspiration pneumonia. Elective for no bulbar dysfunction
Once intubated consider tracheostomy if no pulmonary function improvement within 2 weeks
Treat long-term neuropathic pain: gabapentin
Rehab - individualised in acute phase prevents fatigue and improves quality of life
Prognosis
Medical emergency
2-5% die - due to secondary complications (respiratory paralysis or cardiac arrest)
Most fully recover - remyelination of nerves can take between 6-12months
30% still have residual weakness after 3 years
3% still have weakness/tingling many weeks later
