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.
For patient education information, visit eMedicineHealth's Sexual Health Center. Also, see eMedicineHealth's patient education article HIV/AIDS.
For other discussions on of HIV infection, see Medscape Reference articles HIV Disease, Pediatric HIV Infection, and Antiretroviral Therapy for HIV Infection.
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]
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]
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]
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:
The differential diagnosis includes the following:
Other problems to be considered in the differential diagnosis are as follows:
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 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.