Neurological Symptoms, Not Signs,<br />Are Common in Early HIV Infection

Objective. To examine the cross-sectional prevalence of neurological symptoms and signs in a large cohort of human immunodeficiency virus (HIV)-seropositive men, and determine the relationship of the symptoms to disease stage, immunologic markers, and independent variables from neuropsychological (NP) testing and psychiatric interview. Methods: One hundred-nine controls and 386 HIV-infected volunteers enrolled in the HIV Neurobehavioral Research Center (HNRC) longitudinal study. The majority, without acquired immune deficiency syndrome (AIDS), were screened for alcohol/substance abuse; previous diagnosis of HIV-associated dementia; and HIV-unrelated developmental, neurological, medical, and neurobehavioral conditions which potentially impair cognition; and underwent a structured neurological interview and examination, standardized NP testing, and psychiatric interview as part of a more extensive battery. A large subset (N = 377) underwent lumbar puncture for cerebrospinal fluid (CFS) examination. We examined the relationship of sixteen select but independent variables, using stepwise multiple regressions, from demographic/staging, immunological, NP, and psychiatric domains to neurological symptoms in an effort to identify possible predictors of subclinical nervous systems involvement. Results. All categories of neurological symptoms were significantly more prevalent among medically asymptomatic (CDC stage A) subjects than controls, with a further rise in prevalence in those with more advanced stages of infection. The most marked rise was seen in cognitive and sensorimotor complaints. In contrast, significant findings on neurological examination were evident in only the sicker (stage C) subjects. Stage of illness, serum β2-microglobulin, psychiatric indices of depressed mood or anxiety, and NP "motor" performance were the most significant independent variables associated with the presence of neurological symptoms. CSF pleocytosis was seen early (CDC stage A), and may reflect the presence of HIV in the central nervous system (CNS) at the least stages of infection. We also confirmed the value of CSF β2m and neopterin as important markers of advancing disease stage. Whether they predict subclinical CNS involvement is to be determined by longitudinal observations. Conclusion. Neurological complains are common in medically asymptomatic HIV subjects whereas signs are not. The symptoms correlate with commonly determined independent measures of depression, anxiety, NP tests of fine motor speed and strength, as well as indices of disease worsening (CDC stage, serum β2m).     

Neurologic Manifestations<br />of HIV Infection Without AIDS:Follow-UP of a Cohort<br />of Homosexual and Bisexual Men

To identify neurological abnormalities in HIV infection, 159 HIV-seropositive men without AIDS and 76 seronegative controls underwent standardized general and neurological examinations, lumbar puncture (LP), neuropsychological (NP) assessment, and brain magnetic resonance (MR) imaging. History, physical, and laboratory evaluations were repeated every six months. NP tests (all subjects) and MR imaging (seropositives only) was repeated every 6-12 months; LP (seropositives only) was repeated yearly. Mean follow-up was 24.6 months. Neurological abnormalities, most related to hearing, were seen in 60 (38.2%) of 157 seropositives and 23 (30.3%) of 76 controls at baseline (p = NS). During follow-up, 43 (31.6%) of 136 seropositives had persistent hearing abnormalities compared to 9 (14.1%) of 64 seronegatives (p = 0.008). Seven HIV-seropositives developed peripheral neuropathy; this was more common among those with hearing abnormalities (p = 0.03). HIV-seropositives performed less well on NP tests than controls, but overall performance did not decline. Worsening brain atrophy by MR imaging or cerebrospinal fluid abnormalities are more common in HIV-seropositives than seronegatives and may share a common mechanism with peripheral neuropathy. Further study is needed to determine whether these abnormalities portend more serious neurological disease.     

Effect of zidovudine on cerebrospinal fluid in patients with HIV infection and acute neurological disease.

Two cases of HIV infection associated with neurological complications are described. The patients had been followed with repeated cerebrospinal fluid (CSF) analyses 1-3 years before the neurological disease and 5 months after zidovudine treatment. CSF mononuclear cell count and the AIDS predictors beta 2-microglobulin and neopterin decreased in CSF after treatment and were lower or at the level seen 1-3 years before treatment. The results suggest that zidovudine has a suppressive effect on the HIV infection in CNS at least for 5 months, even when low zidovudine doses (500 mg daily) were used.     

Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features

OBJECTIVE: To define clinical and laboratory features that identify patients with neurosyphilis. METHODS: Subjects (n=326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/ microL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result. RESULTS: Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer > or =1 : 32 increased the odds of neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4+ T cell count < or =350 cells/ microL conferred 3.10-fold increased odds of neurosyphilis in HIV-infected subjects. Similar results were obtained when neurosyphilis was more stringently defined as a reactive CSF VDRL test result. CONCLUSION: Serum RPR titer helps predict the likelihood of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis.     

Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment

STUDY OBJECTIVES: To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement. PATIENTS: Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period. INTERVENTIONS: Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebrospinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis. RESULTS: Treponema pallidum was isolated from the CSF of 12 (30%) of 40 patients (95% CI, 17 to 46) with untreated primary and secondary syphilis; isolation of T. pallidum was significantly associated (P = 0.008) with the presence of two or more abnormal laboratory variables (among leukocyte count, protein concentration, and CSF-Venereal Disease Research Laboratory [VDRL] test). Two (67%) of 3 early latent (CI, 13 to 100) and 3 (20%) of 15 late latent syphilis patients (CI, 5 to 47) also had reactive CSF-VDRL tests and elevated cell and protein levels, although T. pallidum was not isolated. Concurrent infection with the human immunodeficiency virus (HIV) was not associated with isolation of T. pallidum, increased number of CSF abnormalities, or reactive CSF serologic tests for syphilis, although CSF pleocytosis was commoner in subjects infected with HIV. Treatment with conventional benzathine penicillin G (2.4 mIU) failed to cure 3 of 4 patients with secondary syphilis from whom T. pallidum was isolated before therapy; all 3 patients in whom treatment failed were HIV seropositive when treated or seroconverted during follow-up. CONCLUSIONS: Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.     

Neurological symptoms during primary human immunodeficiency virus (HIV) infection correlate with high levels of HIV RNA in cerebrospinal fluid.

This analysis involves 22 patients with diagnosed symptomatic human immunodeficiency virus (HIV) infection. Neurologic symptoms were present in 11 patients, ranging from severe and persistent headache to clinical signs suggestive of meningitis. A strong correlation between neurological symptoms and cerebrospinal fluid (CSF) viral load was found. The mean CSF HIV ribonucleic acid (RNA) level was 4. 12 log for patients with neurological symptoms and 2.58 log for patients without neurological symptoms (P<.00001). Plasma viral load alone does not correlate or predict central nervous system (CNS) involvement. In our sample of patients, HIV RNA levels could be detected in most patients regardless of the presence of neurological symptoms. Moreover, early treatment including drugs with high levels of penetration in the CNS must be considered for patients with primary HIV infection.     

Clinical characteristics,diagnosis, and predictors of neurosyphilis patients with human immunodeficiency virus co-infection: A retrospective study at infectious diseases hospitals in two cities of China

This study aimed to compare between the clinical and laboratory characteristics of neurosyphilis and those of syphilis in human immunodeficiency virus (HIV) positive and explore the risk factors associated with the occurrence of neurosyphilis in the HIV infected.In-patients diagnosed with HIV and syphilis co-infection who underwent a lumbar puncture and completed cerebrospinal fluid (CSF) examination were divided into neurosyphilis group and syphilis group. The demographic characteristics, symptoms and signs, and laboratory tests of the 2 groups were comparatively analyzed. Logistic regression analysis was used to explore the risk factors associated with the occurrence of neurosyphilis.Among 81 patients, 33 patients were assigned to the neurosyphilis group, and 48 to the syphilis group. There were no significant differences in the age, gender, marital status, acquired immunodeficiency syndrome course, opportunistic infections, serum HIV viral load, and history of syphilis treatment. The difference in HIV transmission route between the 2 groups was statistically significant (P = .010), and the patients from the neurosyphilis group were mainly infected via heterosexual contact. The proportion of serum toludine red unheated serum test (TRUST) titer ≥1:16 in the neurosyphilis group were 78.8%, which was significantly higher compared to the syphilis group (48.9%). The level of CSF white blood cell count, CSF protein, and CSF HIV viral load in the neurosyphilis group were significantly higher than those of the syphilis group. The proportion of patients with neurological symptoms and signs in the neurosyphilis group was significantly higher compared to the syphilis group (P < .001). Multivariate logistic regression analysis showed that heterosexual contact transmission route, not received antiretroviral therapy, lower CD4 cell count and higher serum TRUST titer, untreated with syphilis, and neurological symptoms and signs were risk factors associated with the occurrence of neurosyphilis.The serum TRUST titer, CSF white blood cell count, CSF protein level, CSF HIV viral load, and the percentage of neurological symptoms and signs in the neurosyphilis group were higher. Heterosexual transmission route, not received antiretroviral therapy, and untreated with syphilis prompted the possibility of neurosyphilis occurrence.     

Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

Background  

Central nervous system (CNS) exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF) provides a useful window into and model of human CNS HIV infection.     

Elevated neopterin and beta 2-microglobulin levels in blood and cerebrospinal fluid occur early in HIV-1 infection

Neopterin and beta 2-microglobulin (beta 2-M) concentrations in cerebrospinal fluid (CSF) and blood were measured in 56 individuals in various stages of HIV-1 infection. Elevated levels of neopterin as well as beta 2-M were found in the CSF of three patients with primary HIV-1 infection and also in subjects in the early stages of chronic HIV-1 infection, with the highest levels in HIV-1 isolation-positive people. There was a clear correlation between the concentrations of the two substances and the levels seemed to increase in parallel with progress of infection. A similar pattern was found in blood. Higher concentrations of neopterin and beta 2-M in CSF than in blood were found in patients with advanced dementia in particular. These findings indicate that the cellular immune system in the central nervous system (CNS) may be activated during the early stages of HIV-1 infection without concomitant overt neurological symptoms. The pathological processes in CNS and blood seem to develop in parallel rather than being restricted to one compartment.     

未经治疗梅毒患者脑脊液检测的意义

目的　观察艾滋病病毒 (HIV)阴性、未经治疗、且无神经损害临床表现的梅毒患者的脑脊液常规及梅毒抗体的检测情况 ,并探讨这些指标的诊断意义。方法　对 36例未经治疗且无神经系统临床表现的梅毒 (其中二期16例 ,隐性 2 0例 )患者脑脊液进行脑脊液常规、梅毒暗视野检查、聚合酶链反应 (PCR)及脑脊液梅毒抗体试验、梅毒血清快速反应素试验 [(RPR)、IgM、梅毒参比试验 (VDRL)、荧光密螺旋体抗体 (TPPA)、梅毒螺旋体明胶颗粒凝集试验 (FTA Abs) ]检测。结果　在所检测的 36例梅毒患者脑脊液中 ,常规检测发现 2 4例 (6 6 6 7% )蛋白升高 ,11例 (30 6 % )葡萄糖升高 ,未发现红细胞和白细胞 ;有 19例 (5 2 78% )梅毒患者脑脊液存在≥ 1种梅毒抗体。其中 6例 (16 7% )VDRL阳性 ,13例 (36 39% )FTA Abs阳性 ,14例 (38 33% )TPHA阳性 ,RPR、IgM、TP PCR及梅毒暗视野检查均阴性 ;二期和隐性梅毒各项指标检测结果之间差异无显著的统计学意义 (P >0 0 5 ) ;而脑脊液VDRL、FTA Abs、TPPA三种检测结果之间差异有显著的统计学意义 (P <0 0 5 )。结论　未经治疗的梅毒患者其脑脊液存在异常 ,这些异常的结果表明部分未经治疗的梅毒患者存在无症状神经梅毒。     

Increased intrathecal release of soluble fractalkine in HIV-infected patients

The CX(3)C chemokine fractalkine is suggested to play an important role in inflammatory brain diseases, for example, because of its chemotactic properties. To investigate the release of soluble fractalkine in HIV-induced brain diseases fractalkine levels were determined in cerebrospinal fluid (CSF) and serum samples of HIV-infected patients with (n = 10) and without (n = 23) HIV-induced CNS complications, using semiquantitative Western blot analysis. Fractalkine CSF levels were significantly elevated (p < 0.05) in HIV-infected patients with CNS diseases compared with those without, and compared with HIV-negative controls (n = 23). Fractalkine serum concentrations did not differ between the two groups of HIV-infected patients, but were significantly elevated (p < 0.05) in HIV-infected patients with CNS complications compared with HIV-negative controls. Levels of fractalkine did not correlate with the CSF and serum HIV load and other CSF parameters. In one patient with HIV-associated dementia and myelopathy CSF fractalkine levels decreased on initiation of antiretroviral therapy and subsequent clinical improvement. In conclusion, intrathecal fractalkine release was observed in the majority of patients with HIV infection. The highest levels of soluble fractalkine were detected in CSF (and serum) samples of patients with HIV-induced CNS disorders. These results suggest a dysregulation of brain soluble fractalkine release during HIV infection.     

Relationship of cerebrospinal fluid immune activation associated factors to HIV encephalitis.

OBJECTIVES AND DESIGN: Because macrophages are the predominant immune cell and the predominant infected cell in the brains of patients with HIV encephalitis, we studied macrophage and immune activation-associated factors in the cerebrospinal fluid (CSF) from 39 autopsied AIDS cases for whom complete neuropathologic evaluation of the brain was available. RESULTS: CSF HIV p24 antigen was present in less than one-third of cases (11 out of 39). Less than half of the autopsies with moderate to severe parenchymal infection by HIV had high levels of CSF p24, although all autopsies with elevated levels of HIV p24 had moderate to severe HIV encephalitis. Elevated levels of cytokines, beta 2-microglobulin, neopterin, and quinolinic acid were observed. CONCLUSIONS: Although many of the CSF findings showed a strong correlation with each other, none showed a strong correlation with the severity of HIV infection of the brain itself. The absence of a close association between CSF abnormalities and HIV encephalitis could reflect the abundance of complicating opportunistic infections in these terminally ill patients or the inadequacy of CSF as a marker of basal ganglia involvement in HIV encephalitis. These findings complicate interpretation of clinical studies of CSF in patients with AIDS where neuropathologic evaluation is unavailable.     

Calprotectin in cerebrospinal fluid of the HIV infected: a diagnostic marker of opportunistic central nervous system infection?

The calprotectin level in the cerebrospinal fluid (CSF) of 15 HIV positive patients with symptoms from the central nervous system (CNS) was measured. All 5 patients with opportunistic infections had levels above the reference range and all 10 patients with HIV associated encephalopathy had levels within the reference range. Thus, the calprotectin level in CSF can be of diagnostic value in differentiating between HIV associated encephalopathy and opportunistic infection in the HIV positive patient with symptoms from the CNS.     

Serum TRSUT Titer ≥1:16 Is a Predictor for Neurosyphilis Among HIV-Infected Patients With Concurrent Syphilis and No Neurological Symptoms

Investigating the predictors for lumbar puncture to diagnose the asymptomatic neurosyphilis among HIV and syphilis co-infected patients in Shanghai, China.Respectively, screening the medical records from August 1, 2009 to June 30, 2015. Those HIV-infected patients with concurrent syphilis who had received lumbar puncture were selected and their clinical and demographic data were recorded. Participants comprised symptomatic and asymptomatic patients. The latter ones could be further divided into 3 groups: late syphilis, early syphilis with anti-syphilis treatment failure, and early syphilis with serum toludine red unheated serum test (TRUST) ≥1:32. Both syphilis stage and anti-syphilis treatment effect were defined by common criteria, and syphilis of unknown duration was considered as late syphilis. Asymptomatic neurosyphilis was defined as neurosyphilis without neurological symptoms such as headache, cognitive dysfunction, motor deficits, auditory or ophthalmic abnormalities, and stroke. Neurosyphilis was defined as reactive cerebrospinal fluid (CSF) TRUST and/or CSF white blood cell >20 cells/μL without other reasons. Mann–Whitney test and Fisher''s exact test were used for analyzing the difference between neurosyphilis and non-neurosyphilis group. Logistic regression test was performed to analyze the risk factors for neurosyphilis.In total, 170 participants were collected, and the rate of neurosyphilis was 32.35%. Among all the 105 participants without neurological symptoms, 80 patients were with late syphilis and 25 were with early syphilis. Among the early syphilis patients, 23 had a TRUST ≥1:32 and the other 2 experienced an anti-syphilis treatment failure. The differences of clinical and demographic variables between neurosyphilis and non-neurosyphilis group were not statistically significant except the serum TRUST titer (P < 0.01). From HIV/syphilis co-infected patients with or without neurological symptom, those who had neurological symptoms, CD4 <350 per μL and serological TRUST titer ≥1:16 were 4.9-fold (95% confidence interval [CI]: 2.37–10.31), 4.3-fold (95% CI: 1.17–15.78), and 4.1-fold (95% CI: 1.58–10.76), respectively, more likely to be diagnosed with neurosyphilis. Asymptomatic patients whose serum TRUST titer ≥1:16 were 8.48-fold (95% CI: 1.08–66.63) more likely to have asymptomatic neurosyphilis.Among asymptomatic HIV-infected patients with late syphilis or early syphilis experienced an anti-syphilis treatment failure, those who have a serum TRUST titer ≥1:16 are suggested to perform lumbar puncture in order to avoid delayed diagnosis and the occurrence of severe sequelae of syphilis.     

Genetic analysis of HIV type 1 env gene in cerebrospinal fluid and plasma of infected Chinese paid blood donors

HIV infection in the central nervous system (CNS) can progress to AIDS dementia complex (ADC). Currently, the HIV-1 env gene in the CNS of infected Chinese paid blood donors (PBDs) has not been well characterized. In the study, the C2-V5 regions of the HIV env gene were cloned and sequenced from both cerebrospinal fluid (CSF) and plasma samples of six HIV-infected Chinese PBDs. Sequence analysis revealed that the sequences from Henan province clustered closely with subtypes B' and B, and the levels of diversity from the CNS were significantly lower than those from blood (p<0.0001). In addition, all viral quasispecies from CNS use CCR5 as the coreceptor. These data provide valuable information on HIV pathogenesis in the CSF and plasma of infected Chinese PBDs, and our findings could enhance insights into HIV-associated neurological disease.     

Detection of Toxoplasma gondii soluble antigen, SAG-1(p30), antibody and immune complex in the cerebrospinal fluid of HIV positive or negative individuals

Active infection by T. gondii was evaluated by immunoassay for soluble SAG-1 (p30), the major surface antigen from T. gondii, specific antibodies and immune complexes in human cerebrospinal fluid (CSF) samples. A total of 263 samples of CSF were collected from hospitalized patients presenting neurological disorders and analyzed for antibodies to HIV. Patients were divided into two groups: HIV positive (n = 96) or HIV negative (n =167). The results of the assays showed that 45% of all samples were positive for soluble SAG-1. Toxoplasma Ag/Ab immune complexes were detected in 19% of the CSF samples and 62% were positive for T. gondii- specific IgG. A combination of these assays in the presence of clinical findings consistent with active Toxoplasma infection may predict the presence of toxoplasmic encephalitis. Moreover, detection of soluble SAG-1 in the CSF of these individuals appears consistent with active infection.     

Complicações Neurológicas em Pacientes com Endocardite Infecciosa: Perspectivas de um Centro Terciário

Background:Neurological complications are common in patients with infective endocarditis (IE). Recent data suggest that neurologic events are a major determinant of prognosis, and that surgery is critical in improving the outcome.Objective:To characterize patients with IE and neurological complications and to determine predictors of embolization to the central nervous system (CNS) and mortality.Methods:Retrospective analysis of patients admitted to a tertiary center with the diagnosis of IE from 2006 to 2016. Statistical significance was defined by a p-value < 0.05.Results:We identified 148 episodes of IE, 20% of which had evidence of CNS embolization. In patients with CNS embolization, 76% presented with ischemic stroke. During follow-up, 35% were submitted to surgery and both in-hospital and one-year mortality were 39%. These patients had longer hospitalizations, but there were no significant differences regarding mortality in patients with and without CNS embolization. The independent predictors of neurological complications were diabetes (p=0.005) and the absence of fever at presentation (p=0.049). Surgery was associated with lower mortality (0 vs. 58%; p=0.003), while patients with septic shock had a poorer prognosis (75 vs. 25%; p=0.014). In multivariate Cox regression, human immunodeficiency virus (HIV) infection was the only independent predictor of in-hospital and 1-year mortality (p=0.011 in both).Conclusions:In this population, embolization to the CNS was common, more often presented as ischemic stroke, and was associated with longer hospitalization, although without significant differences in mortality. In patients with CNS embolization, those submitted to surgery had a good clinical evolution, while patients with septic shock and HIV infection had a worse outcome. These results should be interpreted with caution, taking into consideration that patients with more severe complications or more fragile were probably less often considered for surgery, resulting in selection bias.     

Macrophage Activation Factors<br />in the Brains of AIDS Patients

HIV, soluble HLA class I (sHLA-I), quinolinic acid (QUIN), and the monokines IL-1β, IL-6, and TNF-α were measured by ELISA and PCR in brain tissue of 60 AIDS autopsies without evidence of CNS opportunistic infections. Individual cases showed good interrogational correlations for the factors measured. There was a positive correlation between concentrations of IL-1β and IL-6. Brain viral burden correlated with intraparenchymal levels of sHLA-I, IL-1β, and IL-6. Comparison of neuritic damage and levels of immune mediators implicates macrophage activation factors in the etiology of neurologic damage in AIDS.     

Blood-Brain Barrier Integrity<br />in HIV Infection:Evaluation by Contrast-Enhanced<br />Magnetic Resonance Imaging

This study assesses the integrity of the blood-brain barrier (BBB) in human immunodeficiency virus (HIV) seropositive individuals to magnetic resonance imaging (MRI) contrast agent Gd-DTPA. Twelve HIV seropositive patients and six control subjects had T2-weighted and serial pre- and post-contrast TI-weighted MRI. Ten of the twelve seropositive patients demonstrated white matter hyperintensity with or without atrophy on T2-weighted MRI and 8/10 who underwent neurological examination demonstrated neurological abnormalities. No statistically significant differences of trends in white matter pixel values were observed between pre- and post-contrast scans in any of the patients or controls. Serial T1-weighted MRI does not demonstrate any change in the integrity of the BBB to Gd-DTPA in HIV seropositive patients, regardless of the presence or absence of white matter hyperintensity with or without atrophy on T2-weighted MRI or clinical signs of HIV-I associated with cognitive/motor complex.     

ANTIBODIES TO HIV ARE PRODUCED WITHIN THE CENTRAL NERVOUS SYSTEM OF ALL SUBJECTS WITH ALL CATEGORIES OF HIV INFECTION

Anti-HIV antibodies were found in the cerebrospinal fluid of all 41 subjects tested whose serum contained these antibodies. To ensure that locally produced antibody was being detected, a sensitive assay was used to demonstrate the integrity of the blood-brain barrier. Antibodies to ubiquitous adenovirus group antigens were sought, simultaneously, in CSF and serum. A lack of adenovirus antibodies in CSF of subjects seropositive for adenovirus was required before CSF anti-HIV antibodies could be considered to be produced within the central nervous system.
Of the 41 subjects tested eight were asymptomatic, eight were clinically well but had persistent lymphadenopathy, 14 were immunodeficient arid had constitutional symptoms (AIDS-related complex or ARC) and 11 had AIDS. Ofigoclonal banding was detected in the CSF of 16 subjects and a pleocytosis was present in 24. Neither finding clustered with a particular stage of infection. It appears that HIV infection of T lymphocytes and the central nervous system occurs simultaneously, early in the course of the infection. All HIV infected subjects are at risk of developing primary neurological as well as immunological sequelae. Currently poorly understood resistance factors must protect both lymphocytes and nervous system tissue from damage by the HIV virus, as to date, the majority of infected subjects have not become immunodeficient or developed neurological disease.