Acute and Chronic Inflammatory Demyelinating Polyneuropathy in HIV

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Overview

Human immunodeficiency virus (HIV) infection is an important cause of inflammatory demyelinating neuropathies. In 2 case series up to 30% of patients presenting with acute inflammatory demyelinating polyradiculoneuropathy (aka Guillain-Barré syndrome) were HIV positive. It is important to exclude HIV infection in any patient who presents with these conditions. The history, physical examination, and course resemble those in HIV-seronegative patients.

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Pathophysiology

While many of the clinical manifestations of HIV infection are caused by immune deficiency, others are a manifestation of the general state of immune activation evidenced by T-cell activation and hypergammaglobulinemia, which can result in autoimmunity.

In HIV-positive patients, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is thought to occur during seroconversion or while CD4 cell counts are still high, and only rarely with low CD4 cell counts. Cytomegalovirus infection must be considered  in patients with acute neuropathy and CD4 counts below 50 cells/μL.

Similar mechanisms are responsible for the increased incidence of AIDP and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in the HIV-positive population. Several in vitro studies have shown that the binding of HIV envelope protein gp120 to chemokine receptors leads to activation of the caspase pathway and axonal degeneration. Perineuronal Schwann cells may have a neuroprotective role.

AIDP rarely can also be seen in the setting of an immune reconstitution inflammatory syndrome (IRIS) when antiretrovirals are initiated in patients with CD4 counts below 100 cells/μL.[1]

One case study suggests that patients with HIV can develop acute motor axonal neuropathy at any stage of the disease process unrelated to CD4 levels. It is hypothesized that this is mediated by a "macrophage activation syndrome" where macrophages attack myelin and nodes of Ranvier induced by cytokines.[16]

Epidemiology

Inflammatory demyelinating neuropathies are diagnosed in one third of HIV-seropositive patients referred for peripheral nerve diseases. While CIDP was more frequent than AIDP in 2 European and North American reports, the converse was true in a larger series of African patients: 16 AIDP but no CIDP patients were found.[2, 3, 4]

Prognosis

The prognosis in patients with HIV-associated AIDP or CIDP is similar to that in HIV-seronegative patients.

For additional information see Acute Inflammatory Demyelinating Polyradiculoneuropathy and Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

One study comparing AIDP in HIV-seropositive versus HIV-seronegative patients found no significant differences between the 2 groups in days spent in the intensive care unit or days ventilated. This was particularly true of HIV-seropositive patients with CD4+ T-cell counts above 200/mL on admission.[5]

Clinical Presentation

AIDP presents most often at seroconversion, rarely in late AIDS.[6]  CIDP can occur at any phase of HIV disease.[7]  HIV-associated AIDP has been associated with more frequent recurrences and with evolution into, rather than among, HIV-seronegative patients.

Characteristic features of inflammatory demyelinating polyradiculoneuropathies include the following:

Differential Diagnosis

The differential diagnosis includes the following:

Other problems to be considered in the differential diagnosis are as follows:

Workup

In HIV-associated AIDP the cerebrospinal fluid (CSF) may demonstrate a mild lymphocytic pleocytosis (10-50 cells/µL), which helps differentiate it from AIDP in HIV-seronegative patients. Similarly, the presence of pleocytosis in a patient with otherwise typical AIDP warrants consideration of underlying HIV disease. Significantly elevated CSF protein is another characteristic finding.

Though CSF pleocytosis may suggest HIV infection, lack of pleocytosis does not exclude HIV infection. CSF pleocytosis can also occur in neurologically intact individuals with HIV infection.

On electromyography/nerve conduction studies, findings are consistent with a primarily demyelinating process, often with secondary axonal degeneration:

Histologic findings include segmental demyelination, mononuclear perivascular infiltration in the endoneurium, perineurial edema, and variable Wallerian degeneration. Viral particles and RNA usually are not present.

Treatment & Management

Treatment is similar to that of HIV-seronegative patients. The goal is to diminish the general state of immune activation, which may be responsible for autoimmunity. Intravenous immunoglobulin (IVIG) and plasmapheresis[8] are preferred to immunosuppression. In patients with CIDP, oral prednisone can be used if benefits are expected to outweigh the risk of further immune suppression.

During a 7 to 10-day period, 4-5 plasmapheresis procedures may be performed. Potential complications include autonomic instability, hypercalcemia, and bleeding caused by depletion of clotting factors.

The choice among IVIG, plasmapheresis, and steroids (for CIDP) must be individualized. The cost of IVIG, the invasive nature of plasmapheresis, and the long-term effects of steroids must be considered. If available, IVIG is a better option.

In advanced HIV disease, with a CD4+ T-cell count of less than 100 cells/µL, opportunistic infections such as cytomegalovirus may need to be investigated and empiric therapy instituted.

Author

Florian P Thomas, MD, PhD, MA, MS, Chair, Neuroscience Institute and Department of Neurology, Director, National MS Society Multiple Sclerosis Center and Hereditary Neuropathy Foundation Center of Excellence, Hackensack University Medical Center; Founding Chair and Professor, Department of Neurology, Hackensack Meridian School of Medicine at Seton Hall University; Professor Emeritus, Department of Neurology, St Louis University School of Medicine; Editor-in-Chief, Journal of Spinal Cord Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Erik Z Krause, DO, Resident Physician, Department of Neurology, St Louis University School of Medicine

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: Received salary from Medscape for employment. for: Medscape.

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

Disclosure: Nothing to disclose.

Chief Editor

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM, Adjunct Associate Professor of Neurology, University of Missouri-Columbia School of Medicine; Medical Director of St Mary's Stroke Program, SSM Neurosciences Institute, SSM Health

Disclosure: Nothing to disclose.

Additional Contributors

Pradeep C Bollu, MD, Assistant Professor of Neurology, Associate Director of Sleep Disorders Center, Associate Director of Neurology Residency Program, Associate Director of Sleep Medicine Fellowship Program, Co-Director of MDA Clinic, Department of Neurology, University of Missouri-Columbia School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Mandeep Garewal, MD, and Sofia Yahya, MD, to the development and writing of the source article.

References

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