Peripheral Neuropathies

HIV-1 infection can be complicated by several neuropathies, including both polyneuropathies and focal neuropathies (Table 411-2) . The most common of these, sometimes called HIV-related distal sensory polyneuropathy, is a distal, predominantly sensory polyneuropathy that manifests in late HIV-1 infection. In this axonal neuropathy, sensory symptoms exceed both sensory and motor dysfunction and severity ranges from asymptomatic increase in sensory thresholds to paresthesias and numbness to severe neuropathic pain. The latter begins with distal burning of the toes or bottoms of the feet and may ascend subacutely or more indolently to the ankles or beyond. Although associated with HIV-1 infection, like the AIDS dementia complex, its pathogenesis is unknown and is speculated to relate to cytokine-mediated injury. Unlike the CNS disease, however, antiretroviral therapy does not appear to reverse the condition. Rather, treatment is directed at relief of pain, using tricyclic antidepressants, gabapentin or, when necessary, narcotic analgesics.

A second and clinically very similar sensory polyneuropathy is caused by some of the nucleoside antiretroviral drugs, including zalcitabine, didanosine, and stavudine.

Clinical differentiation of this dose-related neuropathy from HIV-related polyneuropathy is difficult and relies on temporal linking of onset with drug therapy or its alleviation, after a delay of several weeks, when the drug is stopped. Electromyography or other laboratory studies are not helpful in separating these conditions.

Among the focal neuropathies, CMV causes an uncommon but severe polyradiculopathy that usually begins with pain, weakness and sensory loss in the lumbosacral roots and progresses over days in ascending fashion to affect thoracic and cervical roots. The CSF usually has a characteristic polymorphonuclear cell-predominant pleocytosis. Rapid institution of treatment is paramount in halting its progression which may otherwise be fatal. CMV can also cause a severe mononeuritis multiplex, often involving proximal nerves. This occurs in the setting of low CD4+ lymphocyte counts and also mandates rapid treatment, even without laboratory proof of its cause. It should be distinguished from a more benign and limited mononeuritis multiplex that can occur with higher CD4 counts and likely has an immunopathologic basis.