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The author reviews current treatment approaches for the management of acute immune-mediated peripheral neuropathies, including the Guillain-Barr syndrome together with the clinical variants, which are acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and the Fisher syndrome. A summary of clinical evidence for drug therapies is provided, with additional recommendations for commonly used treatment modalities including a focus on the approach to using intravenous immune globulin and plasma exchange therapy.
Introduction
The acute immune-mediated peripheral neuropathies represent a challenging but treatable array of disorders for the clinical neurologist. Commonly used treatment strategies include therapeutic plasma exchange (PE) and intravenous immune globulin (IVIG). Although these therapies are effective, questions regarding dosing, timing, and concern for adverse events or poor tolerability often hinder their use in clinical practice. For some immune neuropathies, sufficient clinical evidence and guidelines are available to aid the clinician in providing appropriate therapy, as in the case of IVIG for the treatment of Guillain-Barr syndrome (GBS). The term GBS can be used to denote a syndrome that includes acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and variants, or for AIDP alone. Variant neuropathies of GBS include acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and the Fisher syndrome (FS). In the context of treatment, there are more data for AIDP and only limited data for the rare variants. The purpose of this article is to provide helpful information to guide the clinician on the appropriate use of PE and IVIG in GBS, and to provide a brief summary of the evidence for these and other therapies used in the treatment of acute immune-mediated neuropathies.
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Product
Sugar Content
pH
Infusion Rate
Filtration
3, 6, 12 gram vials
Lyophilized 21 powder
96%
720 g/mL
Initial: 0.5 1.67 mg/kg/min grams of Titrate as sucrose 6.46.8 tolerated to Not required per gram maintenance of protein infusion of 3 mg/kg/min Initial: 0.5 mg/kg/min 5 g/100 Titrate as Recommended mL 5.06.0 tolerated to 1520 micron D-sorbitol maintenance infusion of 5 mg/kg/min Initial: 0.8 mg/kg/min Titrate as tolerated to 4.65.1 Not required maintenance infusion of 8.9 mg/kg/min Initial: 0.5 mL/kg/h Titrate as tolerated to maintenance Required 15 6.47.2 rate of 4 micron mL/kg/h (8 mL/kg/h for 10% solution) Initial: 12 mg/kg/min Titrate as 4.04.5 tolerated to Not required maintenance infusion of 8 mg/kg/min Initial: 0.5 mg/kg/min Titrate as tolerated to 5.16.0 Not required maintenance infusion of 3.33 mg/kg/min Initial: 0.5 mg/kg/min Titrate as tolerated to 4.65.0 Not required maintenance infusion of 48 mg/kg/min
3045
97%
<50 g/mL
<3.2 mEq/L
240370 mOsm/L
PID
35
98%
None
90%
Gamunex (Talecris Biotherapeutics, PID ITP Inc., Research CIDP Triangle Park, NC)
35
98%
258 mOsmol/kg
None
PID
40.7
96%
0.2 mg/mL
30 mmol/L
310380 mOsmol/kg
36.6
98%
25 g/mL
Trace
240440 mOsmol/kg
None
CIDP, Chronic inflammatory demyelinating polyradiculoneuropathy; CLL, chronic lymphocytic leukemia; ITP, idiopathic thrombocytopenic purpura; KS, Kawasaki syndrome; PID, primary immunodeficiency. The primary component of IVIG is immunoglobulin G, which is responsible for its therapeutic effects. The usual effective dose of IVIG for inflammatory neuropathies
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is 2 g per kg body weight, typically divided over 2 to 5 days. The rationale for this dose was initially based upon earlier studies of patients with idiopathic thrombocytopenia. The optimal dose of IVIG for neurologic disorders is not conclusively known. Following IVIG infusion, immunoglobulin G rapidly distributes within the intravascular and extravascular compartments with a peak serum concentration typically seen within 72 hours of infusion.[7] Although serum levels of IVIG are generally not measured, a recent pharmacokinetic study of IVIG in AIDP patients suggested that the change in serum immunoglobulin G levels may be predictive of therapeutic responses.[7] The half life of IVIG is ~20 days and immunoglobulins are primarily cleared in the plasma. Dosing of IVIG is typically done using total body weight. For obese patients (>100 kg), many clinicians use an adjusted body weight based upon IVIG pharmacokinetics. IVIG is generally well tolerated. Common adverse reactions include chills, fever, headache, fatigue, rigors, tremor, nausea, myalgias, malaise, and infusion-related reactions. More serious adverse events occur less frequently and include anaphylaxis, aseptic meningitis, acute renal failure, and venous thromboembolism. All patients receiving IVIG should have their vital signs checked at least every 15 minutes during the first hour of infusion and periodically thereafter. Surveillance for tolerability and adverse events should be done judiciously with each infusion session. Pretreatment with acetaminophen, antihistamines, such as diphenhydramine, or corticosteroids may help prevent or minimize adverse events.[8] Markers of renal function should be monitored before each IVIG infusion and periodically thereafter. Appropriate chemical or physical prophylaxis for venous thromboembolism is also warranted. Too rapid rate of infusion may contribute to the incidence of adverse effects. Typically, IVIG infusions are initiated at a slow rate and increased based upon patient tolerability. At any point during an infusion the rate can be decreased to improve tolerability. In general, patients with renal dysfunction should have their rate of infusion decreased by one half of the normal infusion rate. IVIG is expensive and its availability may be limited in some centers. The clinical decision to use IVIG over alternative therapies should be done on an individualized basis and include such factors as pregnancy, disease severity, patient comorbidities, and tolerability.
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Interventional Regimen
Severe Complications
Plasma exchange 5 treatments over Hypotension, arrhythmias, infection, malaise, fever, 7 to 14 days flushing, dizziness, hypocalcemia Intravenous immune globulin 0.4 g/kg daily for 5 days Headache, myalgia, chills, fever, nausea, vomiting, fatigue, tremor, infusion site reactions
Pneumothorax, hemorrhagic complications, sepsis, thromboembolism, anaphylaxis Acute renal failure, thromboembolism, aseptic meningitis, myocardial infarction, anaphylaxis
Summary
Current treatment guidelines recognize PE and IVIG as equally efficacious agents for the treatment of GBS/AIDP.[1] Both agents are clinically proven to hasten the time to recovery and improve disability scores when administered within the early stages of disease progression.[2,6] Due to a lack of data, recommendations for IVIG and PE in the treatment of AMAN, AMSAN, and FS are less well defined, but they are likely reasonable treatment options. The clinical decision as to which agent should be used should be made on an individual basis. In comparative trials, IVIG appeared to be better tolerated and have fewer complications than PE.[6,15]
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Because of this, along with its ease of administration, IVIG is often recommended over PE therapy.[6,15] Despite strong efficacy with these two agents, ~10% of patients will relapse or have an inadequate response following treatment intervention.[14] Risk for relapse is high in patients receiving PE. Repeat administrations of the initial agent may be beneficial in some patients.[14,17] Combination therapies are not recommended.[1] A small number of patients will fail to respond to any treatment and may go on to develop a chronic disability or not survive the initial disease course.[18] For patients with only mild forms of AIDP, few data are available to clarify the role of PE and IVIG. Despite effective therapies and supportive measures, residual functional deficits may persist in approximately one third of patients who experience AIDP.[37]
References
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