In contrast to populations before the era of highly active antiretroviral therapy, DSP in the Manhattan HIV Brain Bank cohort is not associated with increased viral load or decreased CD4 cell counts in this cross-sectional analysis. Symptoms in DSP are associated with substance use disorders, but no difference in morphologic structure is seen in nerves of patients with HIV infection with and without substance use histories. Previously reported virologic and immunologic underpinnings of DSP may be affected by highly active antiretroviral therapy. Furthermore, symptoms of DSP in substance users may be altered by central mechanisms of increased or decreased tolerance to sensory disturbance.

Mice with severe combined immunodeficiency (scid mice) and infected with the relapsing fever agent Borrelia turicatae develop manifestations that resemble those of disseminated Lyme disease. We have characterized two isogenic serotypes, A and B, which differ in their variable small proteins (Vsps) and disease manifestations. Serotype A but not serotype B was cultured from the brain during early infection, and serotype B caused more severe arthritis, myocarditis, and vestibular dysfunction than serotype A. Here we compared the localization and number of spirochetes and the severity of inflammation in scid mice, using immunostained and hematoxylin-and-eosin-stained coronal sections of decalcified heads. Spirochetes in the brain localized predominantly to the leptomeninges, and those in peripheral tissues localized mainly to the extracellular matrix. There were significantly more serotype A than B spirochetes in the leptomeninges and more serotype B than A spirochetes in the skin. The first tissue where spirochetes were observed outside the vasculature was the dura mater. Inflammation was more severe in the skin than in the brain. VspA, VspB, and the periplasmic flagellin protein were expressed in all tissues examined. These findings indicate that isogenic but antigenically distinct Borrelia serotypes can have marked differences in their localization in tissues.Relapsing fever is a disease of humans caused by several species of the genus Borrelia (3). During infection there may be several febrile periods and spirochetemia separated by periods of well-being. The disease is also notable for involvement of the nervous system; manifestations include encephalitis, meningitis, peripheral and cranial neuritis, myelitis, and neuropsychiatric disturbances (9). These bacteria persist in the host through antigenic variation of single surface lipoproteins of two types: variable small proteins (Vsps) of about 23 kDa, and variable large proteins (Vlps) of about 38 kDa. We found that mice with severe combined immunodeficiency (scid mice) infected with Borrelia turicatae, the agent of tick-borne relapsing fever in southwestern North America, develop manifestations that resemble those of disseminated Lyme disease (14). Two serotypes, A and B, differed in the Vsps they expressed and the disease they produced in mice. Overall, serotype B was more virulent than serotype A; it killed infant mice and caused severe arthritis, myocarditis, and vestibular dysfunction (14, 33). Serotype A, on the other hand, was more neurotropic: it infected the brain early in the infection, even though its density in the blood was 10-fold lower than that of serotype B.Serotype A is defined by the expression of VspA, and serotype B is defined by the expression of VspB. The silent and expressed genes for VspA and VspB have been cloned and characterized (13, 33). VspA and VspB are part of a larger family of proteins that includes the Vsps of Borrelia hermsii and the OspCs of the Lyme disease spirochetes B. burgdorferi, B.afzelii, and B. garinii. The sequence ...

Lidocaine 5% gel is a safe but ineffective agent in the treatment of pain in HIV-associated DSP.

Peripheral neuropathy is associated with numerous systemic illnesses including HIV infection. Neuropathic pain constitutes approximately 25-50% of all pain clinic visits. Distal symmetrical polyneuropathy (DSP) is the most common form of peripheral neuropathy in individuals with HIV infection. DSP is distinguished from other forms of neuropathy on the basis of history and neurological examination. The pain associated with DSP can be debilitating. Therefore, it is important to diagnose HIV-associated DSP properly and treat the neuropathic pain in order to improve quality of life. We review the clinical manifestations, epidemiology, pathophysiology and management strategies for HIV-associated DSP.

HCV and biochemical indices of liver function associate differentially with nervous system abnormalities in this HIV-infected population. Neurological abnormalities correlate with biochemical indices of liver function, whereas neuropsychological and psychiatric dysfunction are linked to HCV infection. We postulate that multifactorial impacts of HCV and liver disease on HIV-related nervous system disorders may originate in different anatomical and cellular compartments.