Acute Inflammatory Demyelinating Polyradiculoneuropathy

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Background

Acute inflammatory demyelinating polyneuropathy (AIDP) is an autoimmune process that is characterized by progressive areflexic weakness and mild sensory changes. Sensory symptoms often precede motor weakness. About 20% of patients end up with respiratory failure. Many variants exist. In the West, the most common presentation is a subacute ascending paralysis. This is associated with distal paresthesias and loss of deep tendon reflexes. Progression is often maximal by the end of 4 weeks, then the condition usually plateaus before slowly improving. In 1859, Landry described 10 cases characterized by ascending paralysis and sensory changes.

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.[1] An allergic etiology was suggested by Krucke in 1955 after he observed lymphocytic infiltrates within biopsy specimens.[2] An autoimmune process was supported by Waksman and Adams when they created the experimental allergic neuritis model by injecting peripheral nerve tissue into rodents.[3]

Pathophysiology

Acute inflammatory demyelinating polyneuropathy 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 Guillain-Barré syndrome, axonal degeneration often predominates. Severe Guillain-Barré syndrome 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.

Epidemiology

Frequency

United States

Acute inflammatory demyelinating polyneuropathy is the most common acquired demyelinating polyneuropathy. The incidence is 0.6-1.7 cases per 100,000 per year. No significant seasonal variation has been noted.

International

Frequency is not well documented. Of 2 predominant Guillain-Barré syndrome subtypes, a demyelinating subtype (AIDP) predominates in the United States and Europe, and axonal subtype (AMAN) is the predominant form in China. Previous clinical studies suggested that AMAN also occurs in Mexican children.[4] Similar outbreaks have been reported in Mexico, Spain, and Jordan.

Mortality/Morbidity

In 3 recent large studies, mortality rate ranged from 2-6%.

Race

Acute inflammatory demyelinating polyneuropathy 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.

History

Physical

A detailed physical examination can help support the diagnosis of acute inflammatory demyelinating polyneuropathy and/or exclude disorders in the differential diagnosis.

Causes

Acute inflammatory demyelinating polyneuropathy is thought to be caused by a dysregulated immune response against myelin. This response may be triggered by several illnesses and conditions. Two thirds of patients with AIDP recall an antecedent upper respiratory or gastrointestinal infection or syndrome from 1-6 weeks prior to the onset of weakness.

Laboratory Studies

Imaging Studies

Other Tests

Procedures

Lumbar puncture is performed to obtain CSF for analysis (see Lab Studies).

Histologic Findings

Nerve biopsy is seldom required to diagnose acute inflammatory demyelinating polyradiculoneuropathy. However, in patients with prolonged clinical courses, histologic examination can help to differentiate CIDP from AIDP. Nerve biopsies in AIDP show an inflammatory infiltrate during the first few days.

Later on, macrophages are seen, sometimes with myelin stripping. Axons are usually spared. Under electron microscopy, macrophages (which are stripping myelin) are seen beneath the basement membrane and are usually advancing along the minor dense line.

Medical Care

Advances in supportive medical care have resulted in improved survival rates in acute inflammatory demyelinating polyneuropathy (AIDP).

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.

Activity

Keep patients ambulatory if they are able to walk without assistance. Most patients who are admitted to the hospital require bedrest.

Medication Summary

Immunomodulatory therapy with either IVIg or plasmapheresis has been demonstrated to result in more rapid recovery of AIDP than other treatments or no treatment. Recent large studies have demonstrated that the 2 treatments are equal in efficacy. Bedridden and critically ill patients also require treatment to prevent complications.

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.

Immune globulin IV (IVIg)

Clinical Context:  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).

Plasmapheresis or plasma exchange

Clinical Context:  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.

Class Summary

AIDP is believed to be caused by immune dysregulation resulting from an attack against myelin. Therapy directed at the immune system can result in more rapid recovery. IVIG is especially proven highly effective in children.

Heparin

Clinical Context:  Given subcutaneously, interacts with antithrombin III to decrease clot proliferation. This can result in decreased incidence of deep venous thrombosis.

Class Summary

Bedridden patients are at risk for deep venous thrombosis. This risk can be reduced by mild anticoagulation.

Further Inpatient Care

Based on the severity of symptoms, patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) may require further inpatient services.

Further Outpatient Care

Transfer

Complications

Critically ill patients are susceptible to the same complications as other intubated patients, including pneumonia, sepsis, skin decubiti, deep venous thrombosis, and urinary tract infections. Patients with AIDP have some unique complications that may cause significant morbidity, the most common being pain, labile blood pressure, and increased sensitivity to cardiac medications.

Prognosis

Author

Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital

Disclosure: Abbott Labs None None; Teva Marion None None; Boeringer-Ingelheim Honoraria Speaking and teaching

Coauthor(s)

Richard A Sater, MD, PhD, Consulting Staff, High Point Neurological Associates

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Director of Neurology Clinic, St Louis ConnectCare; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Disclosure: Baxter Grant/research funds Other; Amgen Grant/research funds None

Chief Editor

Nicholas Lorenzo, MD, Consulting Staff, Neurology Specialists and Consultants

Disclosure: Nothing to disclose.

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