Guillain-Barre Syndrome

Definition
Guillain-Barr syndrome (GBS) o Acute, frequently severe autoimmune polyradiculoneuropathy o Characterized by progressive symmetric weakness and loss of deep tendon reflexes Subtypes of GBS determined by electrodiagnostic and pathologic distinctions o Acute inflammatory demyelinating polyneuropathy (AIDP) By far the most common o Acute motor axonal neuropathy (AMAN) o Acute motor and sensory axonal neuropathy o Miller Fisher syndrome

Epidemiology

Incidence
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~0.1 case per 100,000 per month ~3500 cases per year in the U.S. and Canada

Age
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Risk Factors

Affects every age group In Western countries, adults more frequently affected than children o Age distribution varies among subtypes. AIDP: adults more affected than children AMAN: primarily children and young adults Acute motor and sensory axonal neuropathy: mostly adults Miller Fisher syndrome: adults and children Sex o Males are at 1.5-fold higher risk than females. Seasonality o Occurs year-round Antecedent acute infection o ~70% of cases occur 13 weeks after an acute infectious process, usually respiratory or GI. 2030% of all cases in North America, Europe, and Australia are preceded by infection or reinfection with Campylobacter jejuni. o C. jejuni has also been implicated in summer outbreaks of AMAN among children and young adults exposed to chickens in rural China.

A similar proportion is preceded by a human herpes virus infection, often cytomegalovirus (CMV) or Epstein-Barr virus. Other viruses as well as the bacterium Mycoplasma pneumoniaehave been identified as antecedent infections. Recent immunization

Swine influenza vaccine administered widely in the U.S. in 1976 is the most notable example. o Influenza vaccines in use from 19921994 resulted in only 1 additional case of GBS per million persons vaccinated. o Older-type rabies vaccine prepared in nervous system tissue is implicated as a trigger of GBS in developing countries where it is still used.

Etiology
Evidence supports an autoimmune basis for AIDP, the most common type of GBS. o Concept extends to all subtypes. It is likely that both cellular and humoral immune mechanisms contribute to tissue damage. o Circumstantial evidence suggests that all GBS results from immune responses to nonself antigens (infectious agents, vaccines) that misdirect to host nerve tissue through a resemblance-of-epitope (molecular mimicry) mechanism. o It was initially thought to be a T cellmediated disorder. Current data suggest autoantibodies directed against nonprotein determinants, and against gangliosides in particular, may be central in many cases. o In AIDP, anti-GM1 (monosialoganglioside) antibodies may be present, especially with antecedent C. jejuni infection. o In AMAN, variably associated with antibodies against gangliosides GD1a, GM1, GM1b, and GalNAc-GD1a o In Miller Fisher syndrome, 90% associated with anti-GQ1b antibodies o Lymphocytic infiltration of spinal roots and macrophage-mediated demyelination occur. Pathologic findings

AIDP: Initial attack on Schwann cells leads to widespread myelin damage, macrophage activation, and lymphocytic infiltration. Variable secondary axonal damage o AMAN: initial attack on motor neuron nodes of Ranvier, with frequent periaxonal macrophages Extent of axonal damage is highly variable. o Acute motor and sensory axonal neuropathy: same as AMAN, but also affects sensory nerves and roots Axonal damage is usually severe. o Miller Fisher syndrome: very few cases studied; appears to resemble AIDP
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Associated Conditions

Lymphoma, including Hodgkins disease HIV-seropositive individuals Systemic lupus erythematosus

Symptoms & Signs

Overview o Fever and constitutional symptoms are absent at onset. Sensorimotor manifestations o Progressive areflexic motor paralysis Evolves rapidly Usual pattern is ascending paralysis. o First may come to attention as rubbery legs Weakness typically evolves over hours to a few days. o Frequently accompanied by tingling dysesthesias in the extremities. o May reach nadir as late as 4 weeks after onset. o Legs are usually more affected than arms. o Facial diparesis is present in 50%. o Lower cranial nerves are frequently involved; results in bulbar weakness and difficulty with handling secretions and maintaining airway. Deep tendon reflexes usually disappear within the first few days of onset even in muscle groups that maintain some strength. Pain o Pain in the neck, shoulder, back, or diffusely over the spine is common in the early stages, occurring in ~50% of patients.

Deep aching pain in weakened muscles that patients liken to having overexercised the previous day. o Sometimes dysesthetic pain in the extremities, as a manifestation of sensory nerve fiber involvement o Self-limited and should be treated with standard analgesics Cutaneous sensory deficits May or may not occur Loss of pain and temperature sensation Usually relatively mild Bladder dysfunction o May occur in severe cases but is usually transient o Prominent bladder dysfunction early in course should prompt consideration of other possibilities, particularly spinal cord disease. Autonomic involvement o Common in severe cases requiring critical care management Loss of vasomotor control with wide fluctuation in blood pressure, postural hypotension, and cardiac dysrhythmias Requires close monitoring and management Can be fatal Special features of subtypes other than AIDP o AMAN Reflexes are usually preserved. o Acute motor and sensory axonal neuropathy Similar to AMAN, but more severe Sensory symptoms tend to be more severe. o Miller Fisher syndrome Typically presents with ophthalmoplegia, loss of reflexes, and ataxia ~25% develop weakness of the extremities.
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Differential Diagnosis
Acute myelopathies o Especially with prolonged back pain and sphincter disturbances o Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) can present identically to GBS, but course is more persistent. Symptoms may be progressive or relapse and remit. Brainstem ischemia

Diagnostic Approach

Lower cranial nerve involvement by GBS may initially be mistaken for brainstem stroke. Botulism o Pupillary reactivity lost early Diphtheria o Early oropharyngeal disturbances Lyme polyradiculitis and other tick-borne paralyses Porphyria o Abdominal pain, seizures, psychosis o Selective involvement of motor neurons Vasculitic neuropathy o Progressive, asymmetric multifocal mononeuropathies o Erythrocyte sedimentation rate usually elevated Poliomyelitis o Fever and meningismus common CMV polyradiculitis in immunocompromised patients Critical illness neuropathy Neuromuscular disorders such as myasthenia gravis Poisonings with organophosphates, thallium, or arsenic Tick paralysis Paralytic shellfish poisoning Severe hypophosphatemia
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Diagnosis is made by recognizing the pattern of: o Rapidly evolving paralysis with areflexia o Absence of fever or other systemic symptoms o Characteristic history of antecedent infection Required diagnostic criteria o Progressive weakness of 2 or more limbs due to neuropathy (excluding Miller Fisher and other variant syndromes) o Areflexia o Disease course < 4 weeks o Exclusion of other causes, such as: Vasculitis (polyarteritis nodosa, systemic lupus erythematosus, Churg-Strauss syndrome) Toxins (organophosphates, lead) Diphtheria Porphyria Localized spinal cord disorder or cauda equina syndrome Supportive diagnostic criteria o Relatively symmetric weakness o Mild sensory involvement o Facial nerve or other cranial nerve involvement

Laboratory Tests

Absence of fever Typical cerebrospinal fluid (CSF) profile (acellular, increase in protein level) o Electrophysiologic evidence of demyelination In addition to the defined subgroups of GBS, limited or regional GBS syndromes encountered uncommonly include: o Pure sensory forms o Ophthalmoplegia with anti-GQ1b antibodies as part of severe motor-sensory GBS o GBS with severe bulbar and facial paralysis, sometimes associated with antecedent CMV infection and anti-GM2 antibodies o Acute pandysautonomia
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CSF findings o Often normal when symptoms have been present for < 48 hours o By the end of the first week, the protein level is usually elevated. CSF protein 110 g/L (1001000 mg/dL) without accompanying pleocytosis (albuminocytologic dissociation) o Both tau and 14-3-3 protein levels are reported to be elevated early (during the first few days of symptoms) in some cases. o On occasion, a transient mild increase in CSF white cell count (10100/L) occurs early in the course of GBS. o Sustained CSF pleocytosis suggests: An alternative diagnosis (e.g., viral myelitis) or Concurrent diagnosis (e.g., unrecognized HIV infection) Serologic test for HIV in patient with GBS with risk factors for HIV or CSF pleocytosis Serologic tests for antibodies are not clinically available with 1 exception: o Serum IgG antibodies to GQ1b for diagnosis of Miller Fisher Syndrome

Imaging

Not indicated unless needed to rule out other diagnoses o MRI of the spinal cord can help distinguish GBS (normal study) from spinal cord compression or acute myelopathy.

Diagnostic Procedures

Electrodiagnostic features o AIDP: findings of demyelination (see below) o AMAN: axonal findings (see below) o Acute motor and sensory axonal neuropathy: axonal findings o Miller Fisher syndrome: findings of demyelination o Abnormalities are mild or absent in the early stages. o Lag behind the clinical evolution o In cases with demyelination, usual features are: Prolonged distal latencies Conduction velocity slowing Evidence of conduction block Temporal dispersion of compound action potential o In cases with primary axonal pathology: Principal finding is reduced amplitude of compound action potentials. Conduction slowing is absent. Prolongation of distal latencies is absent. o Electrodiagnostic testing can also be helpful in rare instances when a diagnosis of a muscular (e.g., polymyositis) or neuromuscular junction (e.g., myasthenia gravis) disorder must be ruled out. Overview o If the diagnosis of GBS is strongly suspected, initiate treatment without waiting for results of electrodiagnostic and CSF studies. o Most patients require hospitalization. o Almost 30% require ventilatory assistance at some time during the illness. o No treatment completely reverses the process, but intravenous immune globulin (IVIg) therapy or plasma exchange may hasten recovery if initiated early. o Glucocorticoids do not improve recovery time, and are not typically used for treating patients with GBS. o If recovery is prolonged, physical and occupational therapy enhance return to normal activities.

Treatment Approach

Specific Treatments
Immunotherapy ~2 weeks after the first motor symptoms, immunotherapy is no longer effective.

High-dose IVIg therapy and plasmapheresis are equally effective.

Combination of the 2 is not significantly better than either alone. IVIg is often the initial therapy because of ease of administration and good safety record. IVIg is administered as 5 daily infusions; total dose of 2 g/kg body weight. Evidence suggests GBS autoantibodies are neutralized by anti-idiotypic antibodies present in IVIg preparations, perhaps accounting for therapeutic effect. Plasmapheresis o ~4050 mL/kg plasma exchange 4 times over course of a week A brief course of retreatment may benefit patients who initially improve with treatment but relapse in the second or third week.
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Conservative management Very mild cases, especially in patients who appear to have reached a plateau when initially seen, may be managed without IVIg or plasma exchange.

Monitoring
In early phase as GBS is worsening, most patients require monitoring in a critical care setting. o Particular attention to vital capacity, heart rhythm, blood pressure, nutrition, deep vein thrombosis prophylaxis, cardiovascular status, and chest physiotherapy Early consideration (after 2 weeks of intubation) of tracheotomy o ~30% of patients with GBS require ventilatory assistance, sometimes for several weeks or longer. o Frequent turning and assiduous skin care o Daily range-of-motion exercises to avoid joint contractures o Daily reassurance as to the generally good outlook for recovery

Complications

Persistent paralysis Respiratory failure Aspiration Pneumonia

Prognosis
Once clinical worsening stops and the patient reaches a plateau, further progression is unlikely. Recovery is often rapid in AIDP and AMAN, but slow and often incomplete in acute motor and sensory axonal neuropathy. Overall, ~85% of patients achieve a full functional recovery. o Time frame: several months to 1 year o Minor findings on examination (such as areflexia) may persist. o Prognosis has been proved to improve significantly with treatment by plasmapheresis. Need for mechanical ventilation reduced by nearly half, from 27% to 14% Increase in the likelihood of full recovery at 1 year, from 55% to 68% Outlook is worst in patients with severe proximal motor and sensory axonal damage. o Axonal damage may be either primary or secondary. o Successful regeneration is very difficult. Other factors that worsen the outlook for recovery: o Advanced age o A fulminant or severe attack o Delay in the onset of treatment Relapse o May occur in the second or third week in patients who are treated early and improve o Brief retreatment with the original therapy usually effective Late relapses o 510% of patients typically have 1 or more late relapses. These patients are then classified as having CIDP. Mortality rate is < 5% in optimal settings.

Deep vein thrombosis Urinary retention Pressure ulcers Joint contractures

Prevention ICD-9-CM

No preventive measures are currently known. 357.0 Acute infective polyneuritis

See Also

Internet Sites
Professionals o Homepage National Institute of Neurological Disorders and Stroke o Guillain-Barre Syndrome ClinicalTrials.gov Patients o NINDS Guillain-Barre Syndrome Fact Sheet National Institute of Neurological Disorders and Stroke o Guillain-Barre Syndrome MedlinePlus

Approach to Peripheral Neuropathy Chronic Inflammatory Demyelinating Polyneuropathy

General Bibliography
Hughes RA et al: Clinical applications of intravenous immunoglobulins in neurology. Clin Exp Immunol 158 Suppl 1:34, 2009 [PMID:19883422] Hughes RA et al: Practice parameter: immunotherapy for Guillain-Barr syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 61:736, 2003 [PMID:14504313] Hughes RA, Cornblath DR: Guillain-Barr syndrome. Lancet 366:1653, 2005 [PMID:16271648] Hughes RA, Swan AV, van Doorn PA: Corticosteroids for Guillain-Barr syndrome. Cochrane Database Syst Rev 2:, 2010 [PMID:20166061] Hughes RA et al: Supportive care for patients with guillain-barre syndrome.Arch Neurol 62:1194, 2005 [PMID:16087757] Mukerji S et al: Cardiovascular complications of the Guillain-Barr syndrome. Am J Cardiol 104:1452, 2009 [PMID:19892067] Racca F et al: Respiratory management of acute respiratory failure in neuromuscular diseases. Minerva Anestesiol 76:51, 2010 [PMID:20125073] Sharshar T et al: Early predictors of mechanical ventilation in Guillain-Barr syndrome. Crit Care Med 31:278, 2003 [PMID:12545029] Snyder LA, Rismondo V, Miller NR: The fisher variant of guillain-barr syndrome (fisher syndrome). J Neuroophthalmol 29:312, 2009 [PMID:19952907] Winer JB: When the Guillain-Barre patient fails to respond to treatment.Pract Neurol 9:227, 2009 [PMID:19608773] This topic is based on Harrisons Principles of Internal Medicine, 17th edition, chapter 380, Guillain-Barr

Syndrome and Other Immune-mediated Neuropathies by SL Hauser and AK Asbury.

PEARLS
Cardinal feature of GBS is generalized areflexia. Transient back pain is common at the onset of GBS. Vasculitic neuropathy can mimic all of the major features of GBS. In China, seasonal (summer) epidemics of AMAN have occurred due to exposure to C. jejuni. Early respiratory failure in GBS typically manifests as hypercapnia and not hypoxia. o Pulse oximetry is therefore insufficient to monitor patients for progressive respiratory decline.