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Space-occupying Lesions in the Brain

Neurologic disorders are common in persons infected with the human immunodeficiency virus type 1 (HIV-1). Indeed, at autopsy, 70% to 80% of patients with AIDS have pathologic findings in the central nervous system (CNS), including infections, neoplasms, and degenerative conditions of uncertain etiology, such as vacuolar myelopathy; furthermore, diseases within the CNS have become major immediate causes of death in patients with AIDS.
The high prevalence and variety of diseases affecting the CNS is a consequence of the direct involvement of the brain by HIV-1 as well as the profound immunosuppression that occurs as the systemic retroviral illness progresses. Because the spectrum of problems involving the CNS is broad and because many of these conditions respond to specific therapies, the evaluation of the HIV-1–infected patient with neurologic symptoms or signs must be systematic, expeditious, and thorough. This chapter focuses on the prevalent infectious syndromes that involve the meninges and brain. Although the common CNS syndromes are discussed as distinct clinical entities, it must be emphasized that the patient with advanced HIV-1 disease can present with multiple disorders; for example, patients with AIDS can experience cryptococcal meningitis and cerebral toxoplasmosis concurrently.
A neurotropic retrovirus, HIV-1 appears to invade the CNS during the primary infection. The virus has been isolated from the cerebrospinal fluid (CSF) of adults with acute HIV-1 infection and from those with AIDS, and HIV-1 RNA has been detected by polymerase chain reaction (PCR) in the CSF of most patients at all stages of the disease. In addition, HIV-1 has been detected in a number of CNS cell populations, including endothelial cells, macrophages, and microglial cells. Finally, HIV-1 DNA has been found in the brains of about 50% of patients with asymptomatic infection and 100% of patients with AIDS.
Patients with acute HIV-1 infection can present with fever, malaise, myalgias, arthralgias, headache, and photophobia; on occasion, an acute encephalopathy dominates the clinical picture. The CSF abnormalities in patients with acute HIV-1 infection include a lymphocytic pleocytosis (<200 cells per cubic millimeter) and an elevated protein concentration. Thus, the possibility of HIV-1 infection should be considered in the adult who has aseptic meningitis and risk factors for infection with the virus (a history of IV drug use, homosexuality, or heterosexual promiscuity). In the patient with aseptic meningitis and risk factors, PCR or another assay to detect HIV-1 RNA in serum should be performed, and HIV-1 serologies should be obtained 1 and 3 months following the episode to detect seroconversion. The symptoms in patients with acute HIV-1 meningitis usually resolve within 4 weeks. Of note, some patients can experience a chronic meningitis syndrome, apparently caused by HIV-1.
Many patients with latent-stage (asymptomatic) HIV-1 infection have abnormal CSF profiles, typically a lymphocytic pleocytosis (60 mg/dL); these CSF abnormalities may or may not be accompanied by clinical evidence of meningitis. The CSF of patients with AIDS is characterized by an elevated protein level but no pleocytosis. Because of the high prevalence of abnormal spinal fluid findings in this patient population, the results of the CSF analysis must be interpreted with caution in patients who have an enigmatic neurologic process.
Patients with HIV-1 infection are at risk to experience meningitis caused by a variety of microbes, and reports of infection with bacteria (Streptococcus pneumoniae, Listeria monocytogenes), spirochetes (Treponema pallidum), mycobacteria (Mycobacterium tuberculosis, Mycobacterium avium-intracellulare), and fungi (Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis) have appeared in the medical literature. In addition, lymphomatous meningitis can develop in these patients as a complication of a systemic lymphoma. Accordingly, the appropriate microbiologic, serologic, or cytologic tests should be performed in the HIV-infected patient with an acute or chronic meningitis syndrome and epidemiologic, clinical, or laboratory evidence of one of these conditions. Of note, PCR of the CSF for the detection of M. tuberculosis DNA appears to be a very rapid, sensitive, and specific assay for establishing a diagnosis of tuberculous meningitis.
Although uncommonly, HIV-1–infected patients can present with acute syphilitic meningitis or meningovascular syphilis, a dramatic manifestation of neurosyphilis. In addition, these patients are at risk to experience asymptomatic neurosyphilis. Because the spinal fluid Venereal Disease Research Laboratory (VDRL) test in the setting of HIV-1 infection can be nonreactive, the possibility of neurosyphilis should be considered in the patient with positive peripheral blood serologies [VDRL, rapid plasma reagin (RPR)] and compatible cellular and biochemical CSF findings; for example, in one report of 11 patients with oligosymptomatic or asymptomatic neurosyphilis, the CSF VDRL assay was determined to be 100% specific but only 33% sensitive. In any case, T. pallidum can be recovered from the CSF in 20% to 25% of adults with primary or secondary syphilis, and so the potential for relapse within the CNS exists in penicillin-treated, HIV-positive patients. Finally, the utility of T. pallidum DNA PCR in the CSF remains under investigation.
C. neoformans, a fungus found in bird excreta and soil throughout the United States, is the most common cause of nonviral meningitis in patients infected with HIV-1. Before the widespread use of fluconazole, cryptococcal meningitis was reported in about 10% of patients infected with AIDS; the prevalence appears substantially lower at present. Often the initial manifestation of the underlying retroviral disease, cryptococcal meningitis is usually seen in HIV-1–infected patients whose CD4-cell counts are below 100/mm3. The illness presents as a subacute or chronic meningitis syndrome with fever, lethargy, nausea, headache, and nonfocal findings on neurologic examination; papilledema can be present. Results of computed tomography (CT) and magnetic resonance imaging (MRI) are usually normal. The CSF findings are variable, but a pleocytosis, a depressed glucose concentration (hypoglycorrhachia), and an elevated protein level are characteristic; however, in patients with advanced retroviral disease, the spinal fluid cell count, glucose level, and protein level can all be normal. Fortunately, cryptococcal antigen is detectable in the CSF and serum in more than 90% of patients, typically at high titer (>1:1,024). Spinal fluid cultures will reveal the presence of the fungus in virtually all patients, and blood cultures will be positive in 50% to 60% of cases. Higher-dose amphotericin B (0.7 mg/kg per day) with or without flucytosine (100 mg/kg per day) appears to be the treatment of choice for the initial 2 weeks of therapy; fluconazole or itraconazole can be utilized for consolidation therapy. However, some authorities recommend that fluconazole alone be employed as initial therapy in patients with mild disease. Liposomal amphotericin B has also been shown to be effective as initial therapy for crytococcal meningitis, and the use of the agent might be considered in patients who cannot tolerate amphotericin B. In any case, primary therapy for cryptococcal meningitis should be continued until the CSF cultures are sterile. Of note, because of defects in the mechanisms through which the polysaccharide is eliminated, cryptococcal antigen can remain detectable for extended periods of time.
Because relapse occurs in 40% to 60% of treated patients, lifelong suppressive therapy (secondary prophylaxis) is required, and fluconazole (200 mg orally per day) should be used for this purpose. Finally, low-dose fluconazole (200 mg orally thrice weekly) represents effective primary prophylaxis for the infection, and the antifungal should be given to patients with AIDS whose CD4-cell counts are below 100/mm3.
Space-occupying Lesions in the Brain
HIV-1–infected patients frequently present with abnormal findings on the neurologic examination and parenchymal lesions revealed by CT of the brain. Although a number of diseases can result in space-occupying lesions in the brain, the most common entities are toxoplasmosis and lymphoma. Pyogenic brain abscesses, cryptococcomas, tuberculomas, Kaposi’s sarcoma, and even cytomegalovirus (CMV) infection are rare causes of intracerebral masses in these patients.
A protozoan pathogen, Toxoplasma gondii is capable of causing single or multiple cerebral abscesses. The disease usually results from the reactivation of viable organisms encysted in extraneural sites during the primary infection. The risk for cerebral disease approaches 10% among persons with HIV-1 infection who have serologic evidence of prior infection with T. gondii; indeed, toxoplasmosis is the most common cause of intraparenchymal brain lesions in HIV-1–infected patients. The problem is usually seen in persons with CD4-cell counts below 100/mm3.
Most patients with cerebral toxoplasmosis present with focal neurologic problems, such as aphasia, hemiparesis, and complete hemiplegia, that evolve during 1 to 2 weeks; headache, fever, seizures, and changes in mental status also occur. In other patients, toxoplasmosis can present as an acute confusional state, with or without focal findings; these patients can have a diffuse necrotizing encephalitis rather than focal lesions. CT with contrast material will demonstrate single or multiple enhancing lesions in virtually all patients; the lesions are most commonly seen in the region of the basal ganglia or at the junction of the gray and white matter in the cerebral hemispheres. Although the test is not often required, MRI can detect lesions not visualized by CT; with MRI, multiple abscesses will be detected in more than 80% of patients. Toxoplasma serologies are positive in more than 95% of patients with CNS infection. Because the CSF changes are nondiagnostic, the standard analysis of CSF has been considered rarely helpful in the management of these patients; however, PCR of the CSF to detect T. gondii DNA may prove to be a very useful assay. In any case, because the intracranial pressure of patients with intracerebral mass lesions can be increased, a lumbar puncture in this setting does carry a risk for herniation.
Primary lymphoma of the CNS, which has been associated with the Epstein-Barr virus, is the lesion most frequently confused with toxoplasmosis. Although rare in the general population, the disease occurs in about 5% of patients with AIDS; most persons with the malignancy have a CD4-cell count below 50/mm3. In contrast to patients with toxoplasmosis, those with CNS lymphoma tend to present without focal neurologic signs but with a slowly evolving encephalopathy that is characterized by apathy and an altered mental status; nevertheless, the overlap in the clinical manifestations of the two diseases is great. Unfortunately, the anatomic location and CT appearance of toxoplasmosis and lymphoma are similar. Equally important, in up to 40% of patients, the malignancy is multicentric, and so the presence of more than one ring-enhancing lesion on CT does not exclude the possibility of a lymphoma; furthermore, 60% to 70% of patients with primary CNS lymphoma will have positive serologic tests for T. gondii. Of note, in recent investigations, PCR for Epstein-Barr virus DNA in CSF appears to be a very sensitive method for identifying patients with primary CNS lymphoma, and single-photon emission computed tomography (SPECT) with thallium 201 has been reported as a novel method for accurately distinguishing toxoplasmosis from lymphoma.
The approach to the HIV-1–infected patient with a space-occupying brain lesion varies from institution to institution; however, for the AIDS patient with multiple ring-enhancing lesions, empiric antitoxoplasmal therapy is usually given and the clinical response to treatment is monitored. Most patients with cerebral toxoplasmosis demonstrate an improvement in their systemic or neurologic symptoms within 2 weeks and a radiologic response within 3 weeks; of note, abnormalities on CT can persist for up to 6 months. The usual therapy is a combination of pyrimethamine (200 mg by mouth on the first day and then 75 to 100 mg daily), sulfadiazine (1 to 1.5 g orally every 6 hours), and folinic acid (10 to 15 mg daily) given for 4 to 6 weeks; clindamycin (600 mg by vein or by mouth every 6 hours) can be used in patients intolerant of sulfadiazine. When given with pyrimethamine and folinic acid, azithromycin, clarithromycin, and dapsone are among the other agents that have been shown to be effective in the therapy of CNS toxoplasmosis. A stereotactic or open brain biopsy is reserved for patients with single lesions that suggest lymphoma and for patients who fail to respond to antitoxoplasmal therapy within 7 to 14 days.
The outlook for patients with cerebral toxoplasmosis tends to be good, and many survive for extended periods of time. In contrast, the prognosis for patients with primary CNS lymphoma is poor; most succumb within 2 to 4 months. Finally, because the discontinuation of antitoxoplasmal therapy results in a recrudescence of the infection in up to 50% of treated patients, long-term (lifelong) suppressive therapy is indicated; pyrimethamine (25 to 50 mg daily) and folinic acid (5 to 10 mg daily) plus sulfadiazine (0.5 to 1.0 g four times daily) or clindamycin (300 mg four times daily) should be given.
Patients infected with HIV-1 can present with changes in mental status because of meningitis or cerebral mass lesions. These patients can also experience a deterioration in cognitive function caused by intercurrent conditions, including viral encephalitis (CMV, herpes simplex virus, herpes zoster virus, human herpesvirus 6) and metabolic encephalopathy (hypoxemia, drugs). Of note, PCR of the CSF for CMV DNA appears to be a rapid and sensitive technique for establishing a diagnosis of CMV encephalitis or ventriculoencephalitis, and PCR of the CSF has been employed to monitor the response of AIDS patients with CMV disease to antiviral (ganciclovir) therapy.
HIV-infected persons are also at risk for the development of progressive multifocal leukoencephalopathy (PML), which is caused by the reactivation of papovaviruses, usually Jamestown Canyon (JC) virus, and is characterized by personality changes, an altered mental status, aphasia, ataxia, and hemiparesis; occasionally, new-onset seizures are the first manifestation of PML. CT in patients with PML characteristically reveals hypodense, nonenhancing lesions confined to the white matter. Traditionally, a brain biopsy has been required for definitive diagnosis; however, PCR of the CSF for JC virus DNA appears to be a very promising assay. Unfortunately, most patients with PML die within a few months of diagnosis. The most common cause of a deterioration in cognitive function in patients infected with HIV-1, however, is the AIDS dementia complex.
Also referred to as AIDS-related dementia and AIDS encephalopathy, the AIDS dementia complex is characterized by a progressive impairment in cognitive function that is accompanied by behavioral changes and motor abnormalities. Not common in HIV-1–infected persons who are asymptomatic and constitutionally well, the prevalence of the AIDS dementia complex increases with advanced degrees of immunosuppression; the risk for the disorder also rises with age and appears to be greatest in patients with AIDS who are more than 50 years of age. Depending on the criteria used, the disorder has been detected in 25% to 90% of all patients with AIDS. Early in the course, patients with the AIDS dementia complex experience impairments in cognitive function, such as forgetfulness and an inability to concentrate, and personality changes, including apathy, withdrawal, and depression. As the condition progresses, often during a period of months, the cognitive function deteriorates, and the behavioral and motor abnormalities become more prominent; leg weakness, a loss of balance, and clumsiness of the arms and hands are common complaints. Late in the course, ataxia, psychiatric disturbances, mutism, paraplegia, incontinence, and myoclonus occur. Intercurrent illness can accentuate the neurologic findings at any stage. CT reveals cortical atrophy in about 75% of patients with the AIDS dementia complex; the CSF and electroencephalogram findings are usually abnormal, but the changes are not diagnostic of the condition. Most patients succumb within a few months following the onset of severe dementia.
The AIDS dementia complex results from infection of the CNS by HIV-1. The histo-pathology of the brains of many patients is compatible with a diffuse viral infection, suggesting a direct insult by HIV-1; however, the brains of other patients indicate that immune and other indirect mechanisms of injury contribute prominently to the neuropathology. Apoptosis, which is induced by soluble factors, including cytokines (e.g., tumor necrosis factor-a), that are produced by neighboring and uninfected cells, is one important mechanism of neuronal injury. Of note, the magnitude of cytokine production appears to be related to the extent of viral replication. Thus, it is not surprising that clinical investigations have shown that the severity of AIDS dementia complex parallels CSF levels of HIV-1 RNA. A number of other potential mechanisms of neuronal damage have been suggested; these include neurotoxicity by quinolinic acid released by HIV-infected macrophages and cellular injury by HIV-specific cytotoxic T cells. In any case, the severity of the dementia reflects the extent of the pathologic changes in the brain.
Because the CNS changes are attributable to infection with HIV-1, clinicians have been hopeful that antiretroviral therapy would prove useful in the prevention and therapy of the AIDS dementia complex, and initial reports have in general indicated a benefit of antiretroviral drugs. In particular, long-term therappy with zidovudine prevents the onset of neurocognitive defects in patients with symptomatic HIV-1 disease or AIDS, and the medication improves neurocognitive functions, such as memory and attention, in HIV-1–infected patients with AIDS dementia complex; these benefits appear to be sustained for at least months. Didanosine also appears to be effective. The impact of combination antiretroviral therapy (e.g., reverse transcriptase inhibitors plus protease inhibitors) on the incidence and clinical course of AIDS dementia complex remains to be determined. (A.L.E.)
Anaissie E, et al. Central nervous system histoplasmosis. Am J Med 1988;84:215.
The manifestations of CNS histoplasmosis in patients with AIDS include meningitis, multiple brain abscesses, or a single, large, space-occupying lesion.
Appleman ME, et al. Cerebrospinal fluid abnormalities in patients without AIDS who are seropositive for the human immunodeficiency virus. J Infect Dis 1988;158:193.
The authors report that 38.6% of 114 asymptomatic persons infected with HIV-1 had abnormal findings in the CSF.
d’Arminio MA, et al. A comparison of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients. J Neurol 1997;244:35.
The detection of JC virus DNA, CMV DNA, Epstein-Barr virus DNA, or T. gondii DNA by PCR of CSF represents a promising method for establishing etiologic diagnoses in AIDS patients with intracranial lesions.
Arribas JR, et al. Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS and CMV infection of the central nervous system. J Infect Dis 1995;172:527.
The authors conclude that PCR of CSF for CMV DNA is more useful than clinical and neuroradiologic tests to document CMV infection of the CNS and that the levels of CSF DNA correlate with the severity of infection.
Berger JR, et al. Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus. Ann Intern Med 1987;107:78.
Detailed descriptions of the clinical features and radiologic findings of progressive multifocal leukoencephalopathy are provided by the authors, who present 16 patients and review 12 previously reported cases.
Brouwers P, et al. Effect of combination therapy with zidovudine and didanosine on neuropsychological functioning in patients with symptomatic HIV disease: a comparison of simultaneous and alternating regimens. AIDS 1997;11:59.
In this small, nonblinded study, zidovudine and didanosine were both effective in improving memory and attention in patients with AIDS dementia.
Carrigan DR, Harrington D, Knox KK. Subacute leukoencephalitis caused by CNS infection with human herpesvirus 6 manifesting as acute multiple sclerosis. Neurology 1996;47:145.
Human herpesvirus 6 has been added to the list of viral agents that can produce diffuse or multifocal demyelination in the CNS of adults with AIDS.
Chuck SL, Sande MA. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med 1989;321:794.
After a retrospective review of the records of 106 patients with cryptococcal meningitis, the authors concluded that the addition of flucytosine to amphotericin B neither enhances survival nor prevents relapse; in addition, they noted that flucytosine had to be discontinued in 53% of the patients because of leukopenia or thrombocytopenia.
Cinque P, et al. Diagnosis and clinical management of neurological disorders caused by cytomegalovirus in AIDS patients. J Neurovirol 1998;4:129.
The central and peripheral nervous system disorders caused by CMV in patients infected with HIV are reviewed, and the role of PCR of the CSF in the diagnosis and management of the diseases is discussed.
Dannemann B, et al. Treatment of toxoplasmal encephalitis in patients with AIDS: a randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. Ann Intern Med 1992;116:33.
In this study of 59 patients with cerebral toxoplasmosis, the clinical response to therapy and survival were comparable with pyrimethamine (a loading dose of 200 mg orally followed by 75 mg daily) plus sulfadiazine [100 mg/kg body weight (up to 8 g/d) given orally in four divided doses per day] and pyrimethamine plus clindamycin (1,200 mg given intravenously every 6 hours for 3 weeks followed by 300 mg orally every 6 hours).
Dismukes WE. Cryptococcal meningitis in patients with AIDS. J Infect Dis 1988; 157:624.
The author provides a detailed review of the clinical manifestations and laboratory findings of the disease in patients infected with HIV-1.
Epstein LG, Gendelman HE. Human immunodeficiency virus type 1 infection of the nervous system: pathogenic mechanisms. Ann Neurol 1993;33:429.
The authors review the mechanisms through which HIV-1 produces disease in the CNS, emphasizing the role that retrovirus-infected macrophages play in initiating neurotoxicity.
Gabuzda DH, Hirsch MS. Neurologic manifestations of infection with human immuno-deficiency virus. Ann Intern Med 1987;107:383.
Aseptic meningitis, subacute encephalitis, and the other neurologic syndromes attributable to HIV-1 infection are reviewed.
Gorman JM, et al. The effect of zidovudine on neuropsychiatric measures in HIV-infected men. Am J Psychiatry 1993;150:505.
In a prospective, 6-month study of 50 HIV-infected men, a significant improvement in neuropsychiatric parameters was not detected in subjects receiving zidovudine.
Grant I, et al. Evidence for early central nervous system involvement in the acquired immunodeficiency syndrome (AIDS) and other human immunodeficiency virus (HIV) infections. Ann Intern Med 1987;197:828.
Employing extensive neuropsychologic testing, the authors detected abnormalities in 53% of patients with asymptomatic HIV-1 infection, 47% of patients with AIDS-related complex, and 87% of patients with AIDS.
Grant IH, et al. Toxoplasma gondii serology in HIV-infected patients: the development of central nervous system toxoplasmosis in AIDS. AIDS 1990;4:519.
The authors detected antibody to T. gondii in 32% of 411 patients, and they observed that symptomatic CNS infection developed in 24% of the patients with antitoxoplasmal antibodies.
Hollander H. Cerebrospinal fluid normalities and abnormalities in individuals infected with human immunodeficiency virus. J Infect Dis 1988;158:855.
The CSF changes that occur at each stage of infection with HIV-1 are reviewed in detail.
Holton PD, et al. Prevalence of neurosyphilis in human immunodeficiency virus-infected patients with latent syphilis. Am J Med 1992;93:9.
In this study of HIV-1–infected patients with latent syphilis, the investigators found that 9% also had asymptomatic neurosyphilis. The authors conclude that HIV-1–infected persons who have positive results on serum testing for syphilis (VDRL, RPR) should undergo a lumbar puncture to detect evidence of asymptomatic neurosyphilis.
Holtzman DM, Kaku DA, So YT. New-onset seizures associated with human immu-nodeficiency virus infection: causation and clinical features in 100 cases. Am J Med 1989;87:173.
The authors found that although toxoplasmosis and HIV encephalopathy were the most frequently identified causes of recent-onset seizures, the spectrum of infectious and noninfectious causes was broad.
van der Horst CM, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl J Med 1997;337:15–21.
In this double-blind, multicenter trial, patients given a higher dose of amphotericin B plus flucytosine for the initial 2 weeks of therapy demonstrated a higher CSF sterilization rate and a lower mortality rate at 2 weeks than did patients treated with amphotericin B alone; however, the overall case-fatality rates at 10 weeks were similar. Subsequent consolidation therapy was of comparable efficacy with fluconazole or itraconazole.
Johns DR, Tierney M, Felsenstein D. Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus. N Engl J Med 1987;316:1569.
In this report of four HIV-1–infected men with neurosyphilis, the authors note that such patients can present with a variety of clinical illnesses, including acute syphilitic meningitis and meningovascular syphilis. The authors also emphasize that neurosyphilis can evolve in HIV-1–infected persons who have received conventional antimicrobial therapy for early-stage syphilis.
Jurado R, Carpenter SL, Rimland D. Case report: trimethoprim-sulfamethoxazole– induced meningitis in patients with HIV infection. Am J Med Sci 1996;312:27.
A reminder that medications, including trimethoprimsulfamethoxazole, can lead to an aseptic meningitis syndrome.
Kalayjian RC, et al. Cytomegalovirus ventriculoencephalitis in AIDS: a syndrome with distinct clinical and pathologic features. Medicine (Baltimore) 1993;72:67.
The authors describe the unique clinical, CSF, and pathologic findings of this terminal complication of AIDS.
Katz DA, Berger JR, Duncan RC. Neurosyphilis: a comparative study of the effects of infection with human immunodeficiency virus. Arch Neurol 1993;50:243.
In this retrospective review of 46 patients hospitalized with neurosyphilis, the investigators found that the HIV-1–infected group more frequently presented with signs of secondary syphilis and symptomatic meningitis; in addition, a higher WBC count and a lower glucose concentration were usually observed in the CSF of patients with an underlying retroviral infection.
Leenders AC, et al. Liposomal amphotericin B (AmBisome) compared with amphotericin B, both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS 1997;11:1463.
In a study of 28 patients, liposomal amphotericin B (4 mg/kg per day) was found to be less nephrotoxic, have equal clinical efficacy, and produce a more rapid sterilization of the CSF than amphotericin B alone (0.7 mg/kg per day).
Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. Clin Infect Dis 1992;15:211.
The authors provide an in-depth review of the problem and an algorithm useful in the management of patients with space-occupying brain lesions.
Luft BJ, et al. Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. N Engl J Med 1993;329:995.
In a study of 49 patients with suspected CNS toxoplasmosis treated empirically with oral clindamycin (600 mg four times daily) and pyrimethamine (75 mg daily), the authors found that 86% of the patients who responded improved neurologically within 7 days. The investigators also concluded that patients with a presumptive diagnosis of toxoplasmosis who experience an early neurologic deterioration or fail to respond after 10 to 14 days of therapy should be considered candidates for brain biopsy.
Malessa R, et al. Oligosymptomatic neurosyphilis with false-negative CSF-VDRL in HIV-infected individuals. Eur J Med Res 1996;1:299.
Using clinical criteria and the response to antibiotic therapy for neurosyphilis, the authors conclude that the CSF VDRL test was only 33% sensitive in detecting infection with T. pallidum among the 11 HIV-infected patients studied.
Malone JL, et al. Syphilis and neurosyphilis in a human immunodeficiency virus type 1-seropositive population: evidence for frequent serologic relapse after therapy. Am J Med 1995;99:55–63.
Patients with reactive CSF VDRL assays are among those at high risk to experience relapses or treatment failures; these patients require prolonged monitoring and occasionally multiple courses of therapy.
Melton ST, Kirkwood CK, Ghaemi SN. Pharmacotherapy of HIV dementia. Ann Pharmacol 1997;31:457.
A comprehensive review of the AIDS dementia complex, with emphasis on the beneficial effects of zidovudine on the incidence and course of the disorder.
Moulignier A, et al. AIDS-associated cytomegalovirus infection mimicking central nervous system tumors: a diagnostic challenge. Clin Infect Dis 1996;22:626.
The authors report their findings in three patients with AIDS whose clinical and neuroradiologic findings initially suggested neoplasm but in whom brain biopsy confirmed a diagnosis of focal infection caused by CMV.
Murray-Pulsifer K. Two central nervous system infectious diseases in a patient with AIDS. J Fam Pract 1993;36:660.
The author describes a patient with AIDS and concurrent cryptococcal meningitis and toxoplasmal encephalitis.
Powderly WG, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. N Engl J Med 1992;326:793.
In a prospective randomized trial that compared fluconazole (200 mg daily given orally) with amphotericin B (1 mg/kg body weight given weekly intravenously), the investigators found that the relapse rate for symptomatic cryptococcal meningitis was 2% among patients assigned to fluconazole versus 18% among patients administered amphotericin B. In addition, bacteremias and serious drug-related toxicities were more common in the amphotericin B-treated group.
Price RW, Brew BJ. The AIDS dementia complex. J Infect Dis 1988;158:1079.
The clinical manifestations and pathophysiology of the condition are reviewed, and a detailed scheme for the clinical staging of the disorder is presented.
Qureshi AI, et al. Human immunodeficiency virus and stroke in young patients. Arch Neurol 1997;54:1150.
Infection with HIV is associated with an increased risk for stroke and cerebral infarction in young patients.
Rolfs RT, et al. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus unfection. N Engl J Med 1997; 337:307.
The addition of a 10-day course of oral amoxicillin plus probenecid did not improve the efficacy of benzathine penicillin G alone in the therapy of primary or secondary syphilis in HIV-infected patients; clinically defined failure rates were uncommon in both HIV-infected and non–HIV-infected patients.
Schmitt FA, et al. Neuropsychological outcome of zidovudine (AZT) treatment of patients with AIDS and AIDS-related complex. N Engl J Med 1988;319:1573.
Cognitive abnormalities attributable to the AIDS dementia complex may be decreased with the use of zidovudine.
Sidtis JJ, et al. Stable neurological function in subjects treated with 2’3′-dideoxyinosine. J Neurovirol 1997;3:233.
Didanosine (dideoxyinosine, DDI) may have a benefit in the prevention and therapy of AIDS dementia complex similar to that of zidovudine.


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