Nerve Roots (acute polyradiculopathies)Guillain-Barre SyndromeLyme diseaseSarcoidosisHIVOther viruses (CMV, VZV, West Nile)Cauda Equina SyndromePlexus lesions (brachial plexitis, lumbosacral plexopathy)
EpidemiologyMost common cause of acute flaccid paralysis in Western countriesOverall incidence 1-2/100,000; up to 8.6/100,000 in elderly populationAll age groups can be affected, however more common in elderlyBimodal peak, small peak in young adults and larger peak in elderly; rare in infancy
75% have an antecedent event 1-4 weeks before onset of weakness: respiratory (68%), GI (22%), resp and GI (10%), surgery (2%), vaccination or pregnancyThe best documented antecedents included infection with C.jejuni, EBV, CMV, HSV, and Mycoplasma. C. jejuni is often associated with more severe axonal cases and most likely sensitizes the immune system to shared antigens.
Clinical CourseInitial paresthesias in fingers/toes followed by weaknessWeakness rapidly worsens, sensory loss usually minimalUsually symmetric, though can be asymmetric initiallyClassically distal weakness ascending up legs and arms, but proximal weakness not uncommon at onset
Cranial nerve involvement (unilateral or bifacial weakness 50%, oculomotor paralysis 5%, charachteristic in Miller Fischer Syndrome
66% reach nadir in 2 weeks, 92% in 3 weeks; by definition must peak at 4 weeks
Brief plateau phase then improvement and gradual resolution over weeks to months
ComplicationsRespiratory weakness/failure (20-30% will need intubation at some point during admission)Autonomic dysfunction in up to 65% including: arrythmias, hypotension or hypertension, labile fluctuating BP, Ileus, urinary retentionPain in up to 85%: typically back pain, radiculopathic and musculoskeletal, the straight leg raise test will be positive
Papilledema (secondary to high CSF protein)Compression neuropathies (particularly ulnar and peroneal)DVT/PESIADH (26%)Acute Renal Injury (secondary to IVIG TX)Hypercalcemia (secondary to immobility)Hepatocelluar dysfunction (30% early on, as high as 60% later in course
Mortality/Morbidity85% of patients will achieve a full and functional recovery within 6-12 months, maximal recovery at 18 months7-15% of patients will have permanent neurological sequelae including bilateral foot drop, intrinsic hand muscle wasting, sensory ataxia, dysesthesiaDespite intensive care, 3-8% of patients die
Required criteria for typical GBSRequired FeaturesProgressive weakness in both arms and legsAreflexia (or hyporeflexia)
Features supportive of DiagnosisProgression of symptoms over days to 4 weeksRelative symmetricMild sensory signs or symptomsCN involvement, especially bilateral facial weaknessRecovery begins 2-4 weeks after progression ceasesAbsence of fever at onsetTypical CSF and EMG/NCS features
PathophysiologyGBS is believed to result from autoimmune humoral- and cell-mediated responsesto a recent infection or any of a long list of medical problems. Antibodies formed against ganglioside-like epitopes in the lipopolysaccharide (LPS)layer of some infectious agents have been shown in both necropsy and animal models to cross-react with the ganglioside surface molecules of peripheral nerves.
Symptoms generally coincide pathologically with various patterns of lymphocytic infiltration and macrophage-mediated demyelination, depending on the subtype in question. In a subset of patients, GBS is associated primarily with myelin-sparing axonal damage resulting from a direct cellular immune attack on the axon itself.
Types/VariantsAcute Inflammatory Demylinating Polyradiculoneuropathy (AIDP)Acute Motor-Sensory Axonal Neuropathy (AMSAN)Acute Motor Axonal Neuropathy (AMAN)Miller Fisher VariantPharyngeal-Cervical-Brachial VariantAcute Pandysautonomia
Acute Inflammatory Demylinating Polyradiculoneuropathy (AIDP)Most common variant, 85% of casesPrimarily MotorGenerally preceded by bacterail or viral infectionLymphocytic infiltration and macrophage mediated demylination of periopheral nerves is presentSymptoms generally resolve with remylination, max of 4 weeks of progression
Acute Motor-Sensory Axonal NeuropathyMotor and sensory involvement with severe courseRespiratory and bulbar involvementPrimary axonal degenerationPatients are typically adults with both motor and sensory dysfunction with marked muscle wasting and poor recovery
Acute Motor Axonal Neuropathy (AMAN)Motor only with early and severe respiratory involvement, primary axonal degenerationMore prevalent amongst pediatric age groupsUp to 75% positive for C. jejuni serology, often also anti-GM1, anti-GD1a positiveHypereflexia is significantly associated with the presence of anti-GM1 antibodiesCharacterized by a rapidly progressive weakness, ensuing respiratory failure, and good recovery.
Miller Fisher VariantTriad: opthalmoplegia, sensory ataxia, areflexia5% of all cases96% positive for anti-GQ1b (antiganglioside) antibodiesPatients may also have mild limb weakness, ptosis, facial palsy, or bulbar palsy.The ataxia tends to be out of proportion to the degree of sensory loss.Recovery generally occurs within 1-3 months
Pharyngeal-Cervical-Brachial VariantOften associated with IgG anti-GT1aPresents with proximal descending weaknessMust distinguish from botulism and diptheria
Acute PandysautonomiaWidespread sympathetic and parasympathetic failureVery rareCardiovascular involvement is common, and dysrhythmias are a significant source of mortality in this form of diseaseRecovery is gradual and often incomplete
WorkupClinical DiagnosisElevated or rising protein levels on serial lumbar punctures and 10 or fewer mononuclear cells/mm very presumptiveNormal CSF protein does not rule out GBS as the level may remain normal in 10% of patients, and a rise in the CSF protein level may not be observed until 1-2 weeks after the onset of weakness
ImagingMRI is sensitive but nonspecificSpinal nerve root enhancement with gadolinium is a nonspecific feature seen in inflammatory conditions and is caused by disruption of the blood-nerve barrierSelective anterior nerve root enhancement appears to be strongly suggestive of GBSThe cauda equine nerve roots are enhanced in 83% of patients
Nerve Conduction StudiesA delay in F waves is present, implying nerve root demyelinationCompound muscle action potential (CMAP) amplitude may be decreasedPatients may evidence of conduction block or dispersion of responses at sites of natural nerve compression. The extent of decreased action potentials correlates with prognosis
TreatmentOnly plasmapheresis (the exchange of patients plasma for albumin) and intravenous serum globulin (IVIG) have proven effectiveBoth therapies have been shown to shorten recovery time by as much 50%Combining plasma exchange and IVIG neither improved outcomes nor shortened the duration of illnessCorticosteriods are ineffective as monotherapy
IVIGRandomized trials in severe disease show that IVIG started within 4 weeks from onset hastens recovery as much as pasmapheresisDosed at 0.4 gram/kg/day IV for 5 DaysSame dose in pediatricsMay increase serum viscosity and tromboembolic eventsMay increase frequency of migrainesMay cause aseptic meningitis
Sequela of IVIGIncreased antiviral and antibacterial antibody titers for one monthSix-fold increase in ESR lasting two to three weeksApparent hyponatremia