Nov 22, 2007

Acute Inflammatory Demyelinating Polyradiculoneuropathy

During World War I, Guillain, Barré, and Strohl described a series of patients with a similar presentation and decreased or absent deep tendon reflexes. They also described albuminocytologic dissociation in the cerebrospinal fluid (CSF), ie, increased CSF protein in the absence of increased WBCs. This allowed them to differentiate AIDP from poliomyelitis, the most common acute paralytic syndrome of that era. (AIDP often is referred to as Guillain-Barré syndrome [GBS]).

Myelin breakdown and axonal degeneration were observed in nerve biopsies from patients with AIDP by Haymaker and Kernohan in 1949. An allergic etiology was suggested by Krucke in 1955 after he observed lymphocytic infiltrates within biopsy specimens. An autoimmune process was supported by Waksman and Adams when they created the experimental allergic neuritis model by injecting peripheral nerve tissue into rodents.

Pathophysiology: AIDP is believed to be caused by an immunologic attack that is directed against myelin components. This results in a demyelinating polyneuropathy. Both cellular and humoral immune mechanisms appear to play a role. Early inflammatory lesions consist of a lymphocytic infiltrate that is adjacent to segmental demyelination. Macrophages are more prominent several days later.

The peripheral nerve changes consist of varying degrees of perivascular edema, accumulations of mononuclear cells, and paranodal and less commonly, segmental demyelination. They are often multifocal with some predilection for the nerve roots, sites of entrapment, and distal ends. In the axonal variant of GBS, axonal degeneration often predominates. Severe GBS is often associated with axonal degeneration as well, which results in wallerian degeneration. Axonal degeneration occurs either as a primarily axonal process or as a bystander-type axonal degeneration, associated with demyelination. Rarely, the pathologic process extends into the central nervous system.

As the regeneration occurs, nerve sprouting and increased scarring often results.

With electron microscopy, macrophages are observed stripping off the myelin sheath. Humoral molecules such as antimyelin antibodies and complement likely contribute to the process by directing macrophages to Schwann cells by opsonization. Indeed, complement and antibodies have been found to coat the myelin sheath. The changes are observed in nerve roots, peripheral nerves, and cranial nerves. In acute motor axonal neuropathy (AMAN, an AIDP variant), deposited complement is found at the nodes of Ranvier, while myelin often is left undamaged.

Damage to the myelin sheath leads to segmental demyelination. This results in decreased nerve conduction velocity and, at times, conduction block. In this current review, AIDP refers to the more common demyelinating form unless otherwise specified.

Frequency:

Mortality/Morbidity: In 3 recent large studies, mortality rate ranged from 2-6%.

Race: AIDP occurs in all races and in all regions of the world.

Sex: The male-to-female ratio is 1.1-1.7:1.

Age: Patients have ranged in age from 2 months to 95 years.

Surgical Care: Tracheostomy is necessary in many intubated patients. Those requiring long-term enteral nutrition typically require a gastrostomy or jejunostomy.

Consultations:

Diet: No special diet is required.

The mechanism of action of plasma exchange is not known. Suggested mechanisms include the removal of antibody, complement components, immune complexes, lymphokines, and acute-phase reactants. The generally recommended regimen includes every other day plasma exchange, totaling 6 exchanges in 2 weeks, with 3-3.5 L exchanged per treatment. If venous access is not of sufficient quality to ensure rapid blood withdrawal, a central line should be a consideration (in about 20% of cases).

Plasmapheresis (PE) is more frequently associated with severe adverse effects requiring cessation of therapy, including a bleeding diathesis. In addition, PE requires special, appropriate equipment and trained personnel. Also, younger children may be at risk for bleeding after insertion of wide catheters. Transient hypotension, which might occur, is corrected by adjusting the inflow-to-outflow ratio. Other common side effects include paresthesias, and rarely hypersensitivity reactions and hypocalcemia.

Drug Name
IV Immunoglobulin (IVIg) or gamma globulin (many manufacturers) -- IVIg is prepared from serum pooled from many donors by fractionation and purification. Most manufacturers include a detergent step to help prevent spread of viruses. Mechanism of action is poorly understood. However, it is believed to act by down-regulating antibody and cytokine production and by neutralizing antibodies specific for myelin. Also appears to down-regulate pro-inflammatory cytokines, such as IL-1 and gamma-IFN. Other proposed mechanisms are Fc receptor blockade and interference with complement cascade (ie, interfering with opsonization).
Adult Dose0.4 g/kg/d for 5 d has been used most often
Alternative regimen is 1-2 g/kg/d for 2 d
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; IgA immunodeficiency (if present, low-IgA preparations available)
Severe congestive heart disease is relative contraindication
InteractionsNone reported
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCommon adverse effects include headache and itching—pretreatment with acetaminophen and diphenhydramine help prevent these effects
Patients with prior cardiac history are at risk for pulmonary edema—if it occurs, furosemide is drug of first choice
Rarer adverse effects include aseptic meningitis, stroke, skin rashes, renal tubular necrosis; hepatitis C has been transmitted by IVIg in past, but current preparations include detergent step
Can artificially decrease serum sodium and elevate ESR
Drug Name
Plasmapheresis or plasma exchange -- This treatment entails removing blood from body, spinning it to separate cells from plasma, and replacing cells suspended in fresh frozen plasma, albumin, or saline. Can be performed using either 2 large-bore peripheral IV sites or multiple lumen central line.
May not be effective if started more than 2 wk after onset of symptoms.
Adult DoseTypical protocol: 200-250 mL/kg for each of 4 or 5 exchanges during an 8- to 10-d period
Pediatric DoseAdminister as in adults
ContraindicationsRecent myocardial infarction; coronary artery disease; arrhythmias; severe renal failure; severe hepatic failure; bleeding disorder
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsBack-to-back plasmapheresis sessions may remove clotting factors and can alter coagulation test results
Common adverse effects include headaches
Rare cases of myocardial infarction and stroke have been reported
Drug Name
Heparin -- Given subcutaneously, interacts with antithrombin III to decrease clot proliferation. This can result in decreased incidence of deep venous thrombosis.
Adult Dose5000 U SC tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia
InteractionsDigoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsSome preparations contain benzyl alcohol as preservative and, when used in large amounts, may be associated with fetal toxicity (ie, gasping syndrome); preservative-free heparin recommended in neonates
Use with caution in patients with shock or severe hypotension