HIV-associated peripheral neuropathy: epidemiology, pathophysiology and treatment

Abstract

Peripheral neuropathy is the most frequent neurological complication associated with human immunodeficiency virus type 1 (HIV) infection and advanced acquired immunodeficiency syndrome (AIDS). There are at least 6 patterns of HIV-associated peripheral neuropathy, although these diagnoses are often overlooked or misdiagnosed. Distal symmetrical polyneuropathy (DSP) is the most common form of peripheral neuropathy in HIV infection. DSP occurs mainly in patients with advanced immunosuppression and may also be secondary to the neurotoxicity of several antiretroviral agents. Treatment of painful DSP is primarily symptomatic, while pathogenesis-based therapies are under investigation. Reduction or discontinuation of neurotoxic agents should be considered if possible. Inflammatory demyelinating polyneuropathy (IDP) can present in an acute or chronic form. The acute form may occur at the time of primary HIV infection or seroconversion. Cerebrospinal fluid lymphocytic pleocytosis (10 to 50 cells/mm3) is helpful in the diagnosis of HIV-associated IDP. Treatment consists of immunomodulatory therapy. Progressive polyradiculopathy (PP) most commonly occurs in advanced immunosuppression and usually is caused by cytomegalovirus (CMV) infection. Rapidly progressive flaccid paraparesis, radiating pain and paresthesias, areflexia and sphincter dysfunction are the cardinal clinical features. Rapid diagnosis and treatment with anti-CMV therapy are necessary to prevent irreversible neurological deficits resulting from nerve root necrosis. Mononeuropathy multiplex (MM) that occurs in early HIV infection is characterised by self-limited sensory and motor deficits in the distribution of individual peripheral nerves. In advanced HIV infection, multiple nerves in two or more extremities or cranial nerves are affected. Treatment includes immunomodulation or anti-CMV therapy. Autonomic neuropathy may be caused by central or peripheral nervous system abnormalities. Treatment is supportive with correction of metabolic or toxic causes. Diffuse infiltrative lymphocytosis syndrome (DILS) presents as a Sjögren's-like disorder with CD8 T cell infiltration of multiple organs. Antiretroviral therapy and steroids may be effective treatments.