Normalisation of Cerebrospinal Fluid Biomarkers Parallels Improvement of Neurological Symptoms Following HAART in HIV Dementia--case Report

Overview

Journal BMC Infect Dis

Publisher Biomed Central

Specialty Infectious Diseases

Date 2006 Sep 19

PMID 16978408

Citations 5

Authors

Lars-Magnus Andersson

Lars Hagberg

Lars Rosengren

Dietmar Fuchs

Kaj Blennow

Magnus Gisslen

Affiliations

Soon will be listed here.

Abstract

Background: Since the introduction of HAART the incidence of HIV dementia has declined and HAART seems to improve neurocognitive function in patients with HIV dementia. Currently, HIV dementia develops mainly in patients without effective treatment, though it has also been described in patients on HAART and milder HIV-associated neuropsychological impairment is still frequent among HIV-1 infected patients regardless of HAART. Elevated cerebrospinal fluid (CSF) levels of markers of neural injury and immune activation have been found in HIV dementia, but neither of those, nor CSF HIV-1 RNA levels have been proven useful as diagnostic or prognostic pseudomarkers in HIV dementia.

Case Presentation: We report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral naïve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART. Improvement of neurocognitive function was paralleled by normalisation of CSF neural markers (NFL, Tau and GFAP) levels and a decline in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels.

Conclusion: The value of these CSF markers as prognostic pseudomarkers of the effect of HAART on neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal studies.

Citing Articles

HIV-Associated Neurocognitive Impairment in the Modern ART Era: Are We Close to Discovering Reliable Biomarkers in the Setting of Virological Suppression?.

Bandera A, Taramasso L, Bozzi G, Muscatello A, Robinson J, Burdo T Front Aging Neurosci. 2019; 11:187.

PMID: 31427955 PMC: 6687760. DOI: 10.3389/fnagi.2019.00187.

Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.

Anesten B, Yilmaz A, Hagberg L, Zetterberg H, Nilsson S, Brew B Neurol Neuroimmunol Neuroinflamm. 2016; 3(6):e300.

PMID: 27868081 PMC: 5104266. DOI: 10.1212/NXI.0000000000000300.

HIV/neuroAIDS biomarkers.

Rahimian P, He J Prog Neurobiol. 2016; 157:117-132.

PMID: 27084354 PMC: 5705228. DOI: 10.1016/j.pneurobio.2016.04.003.

Should antiretroviral therapy for HIV infection be tailored for intracerebral penetration?.

Koopmans P, Ellis R, Best B, Letendre S Neth J Med. 2009; 67(6):206-11.

PMID: 19749389 PMC: 5077299.

Antiretroviral therapy and central nervous system HIV type 1 infection.

Price R, Spudich S J Infect Dis. 2008; 197 Suppl 3:S294-306.

PMID: 18447615 PMC: 2628635. DOI: 10.1086/533419.

References

Robertson K, Fiscus S, Kapoor C, Robertson W, Schneider G, Shepard R . CSF, plasma viral load and HIV associated dementia. J Neurovirol. 1998; 4(1):90-4. DOI: 10.3109/13550289809113485. View

Bouwman F, Skolasky R, Hes D, Selnes O, Glass J, Royal W . Variable progression of HIV-associated dementia. Neurology. 1998; 50(6):1814-20. DOI: 10.1212/wnl.50.6.1814. View

Wiley C, Soontornniyomkij V, L Radhakrishnan , Masliah E, Mellors J, Hermann S . Distribution of brain HIV load in AIDS. Brain Pathol. 1998; 8(2):277-84. PMC: 8098236. DOI: 10.1111/j.1750-3639.1998.tb00153.x. View

Takahashi K, Wesselingh S, Griffin D, McArthur J, Johnson R, Glass J . Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry. Ann Neurol. 1996; 39(6):705-11. DOI: 10.1002/ana.410390606. View

Petito C, Cash K . Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann Neurol. 1992; 32(5):658-66. DOI: 10.1002/ana.410320509. View

McArthur J, Griffin D, Hoover D, Selnes O, Miller E, Margolick J . The diagnostic utility of elevation in cerebrospinal fluid beta 2-microglobulin in HIV-1 dementia. Multicenter AIDS Cohort Study. Neurology. 1992; 42(9):1707-12. DOI: 10.1212/wnl.42.9.1707. View

Abdulle S, Hagberg L, Gisslen M . Effects of antiretroviral treatment on blood-brain barrier integrity and intrathecal immunoglobulin production in neuroasymptomatic HIV-1-infected patients. HIV Med. 2005; 6(3):164-9. DOI: 10.1111/j.1468-1293.2005.00281.x. View

Studahl M, Rosengren L, Gunther G, Hagberg L . Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction. J Neurol. 2000; 247(8):636-42. DOI: 10.1007/s004150070134. View

Dougherty R, Skolasky Jr R, McArthur J . Progression of HIV-associated dementia treated with HAART. AIDS Read. 2002; 12(2):69-74. View

10.

Hagberg L, Fuchs D, Rosengren L, Gisslen M . Intrathecal immune activation is associated with cerebrospinal fluid markers of neuronal destruction in AIDS patients. J Neuroimmunol. 2000; 102(1):51-5. DOI: 10.1016/s0165-5728(99)00150-2. View

11.

Marshall D, Brey R, Butzin C, Lucey D, Abbadessa S, Boswell R . CSF changes in a longitudinal study of 124 neurologically normal HIV-1-infected U.S. Air Force personnel. J Acquir Immune Defic Syndr (1988). 1991; 4(8):777-81. View

12.

Marra C, Lockhart D, Zunt J, Perrin M, Coombs R, Collier A . Changes in CSF and plasma HIV-1 RNA and cognition after starting potent antiretroviral therapy. Neurology. 2003; 60(8):1388-90. PMC: 2683839. DOI: 10.1212/01.wnl.0000058768.73358.1a. View

13.

Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E . Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?. Mol Chem Neuropathol. 1995; 26(3):231-45. DOI: 10.1007/BF02815140. View

14.

Rosengren L, Karlsson J, Karlsson J, Persson L, Wikkelso C . Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF. J Neurochem. 1996; 67(5):2013-8. DOI: 10.1046/j.1471-4159.1996.67052013.x. View

15.

Norgren N, Rosengren L, Stigbrand T . Elevated neurofilament levels in neurological diseases. Brain Res. 2003; 987(1):25-31. DOI: 10.1016/s0006-8993(03)03219-0. View

16.

Fuchs D, Chiodi F, Albert J, Asjo B, Hagberg L, Hausen A . Neopterin concentrations in cerebrospinal fluid and serum of individuals infected with HIV-1. AIDS. 1989; 3(5):285-8. DOI: 10.1097/00002030-198905000-00006. View

17.

Schacker T, Collier A, Hughes J, Shea T, Corey L . Clinical and epidemiologic features of primary HIV infection. Ann Intern Med. 1996; 125(4):257-64. DOI: 10.7326/0003-4819-125-4-199608150-00001. View

18.

Gisslen M, Rosengren L, Hagberg L, Deeks S, Price R . Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment interruption in HIV-1 infection. AIDS Res Ther. 2005; 2:6. PMC: 1198215. DOI: 10.1186/1742-6405-2-6. View

19.

. Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Report of a Working Group of the American Academy of Neurology AIDS Task Force. Neurology. 1991; 41(6):778-85. DOI: 10.1212/wnl.41.6.778. View

20.

Elovaara I, Seppala I, Poutiainen E, Suni J, Valle S . Intrathecal humoral immunologic response in neurologically symptomatic and asymptomatic patients with human immunodeficiency virus infection. Neurology. 1988; 38(9):1451-6. DOI: 10.1212/wnl.38.9.1451. View