Dr Faktorovich is Assistant Professor of Neurology (pending), Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY; Dr Simpson is Professor of Neurology, Icahn School of Medicine, Mt Sinai, New York, NY.
Human immunodeficiency virus (HIV) is responsible for a wide spectrum of neurologic manifestations, with etiologies ranging from inflammatory, infectious, neoplastic. and more. The development of antiretroviral therapy (ART) has dramatically increased life expectancy, however neurologic complications remain a significant cause of long-term disability. Understanding and recognizing these conditions is crucial in effectively managing HIV patients.
Peripheral neuropathy is the most common neurological complication in HIV/AIDS, it affects between 30% to 60% of individuals. It can be related to the virus itself, ART neurotoxicity, and other comorbidities. Distal sensory polyneuropathy (HIV-DSP) is the most common type of peripheral neuropathy, typically presenting with ascending numbness, paresthesia, and burning-type pain that occurs in a “stocking-glove” distribution.
Neurological evaluation reveals depressed ankle reflexes, increased vibratory threshold, and decreased sensation to pain and temperature. Proprioceptive loss, muscle weakness, and atrophy can be seen late in the disease course. Electrodiagnostic testing demonstrates a symmetrical, sensorimotor axonal neuropathy. Skin biopsy may also be useful, given the loss of epidermal nerve fibers which has been shown to correlate with clinical severity of DSP.1
In the pre-ART era, HIV-DSP was associated with high viral load and low CD4 count. However, since the development of ART, this association has not been clearly demonstrated. Furthermore, some anti-retroviral agents, specifically dideoxy-nucleoside reverse transcriptase inhibitors have neurotoxic effects on peripheral nerve. Although the presentation can be similar, drug-related peripheral neuropathy is typically rapidly progressive, often within weeks of initiating an offending agent. Recognition is important, as the neuropathy typically improves with discontinuing the agent.
Inflammatory demyelinating polyneuropathy
HIV-related, inflammatory demyelinating polyneuropathy can occur at any point in the disease course, presenting in the acute or chronic form, similar to non-HIV related inflammatory demyelinating polyneuropathy. Acute inflammatory demyelinating polyneuropathy typically occurs as a monophasic illness, with symptoms peaking around 2 weeks followed by variable recovery time. It is more commonly seen with CD4 count of greater than 200 cells/mm3 (eg, during seroconversion).2 Chronic inflammatory demyelinating polyneuropathy progresses over 8 weeks or more. Clinical presentation usually involves progressive, ascending weakness that starts in the legs. Pain accompanies the condition in more than 80% of cases, described as dysesthesias and/or deep, aching pain in the legs or lower back.3 Symptoms are notable for areflexia, ascending weakness, and relative sparing of sensation although some sensory impairment can occur. As in HIV negative individuals, these conditions are thought to be immune-mediated. In advanced AIDS, additional studies (ie, viral testing and nerve biopsy) may be necessary to rule out primary cytomegalovirus (CMV) infection of the peripheral nerve.
Electrodiagnostic testing typically reveals a primarily demyelinating, sensorimotor neuropathy, although secondary axonal loss may occur, especially in chronic inflammatory demyelinating polyneuropathy. Unlike seronegative patients where high protein without pleocytosis in the cerebral spinal fluid is a classic finding; cerebrospinal fluid testing is less reliable in the HIV population. HIV patients can have mild lymphocytic pleocytosis. MRI studies are usually normal, however may reveal evidence of nerve root enhancement.
Treatment of these conditions relies on immunomodulatory therapies such as intravenous immunoglobulin, plasmapheresis, and with caution, steroids, as well as neuropathic pain medications as needed.
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