title: Peripheral neuropathy in primary HIV infection associates with systemic and central nervous system immune activation.
abstract: BACKGROUND
  Peripheral neuropathy (PN) is a frequent complication of chronic HIV infection. We prospectively studied individuals with primary HIV infection (<1 year after transmission) to assess the presence of and laboratory associations with PN in this early stage.
  
  
  METHODS
  Standardized examination and analysis of blood and cerebrospinal fluid (CSF) was performed in participants with laboratory-confirmed primary HIV infection. PN was defined as ≥1 of the following unilateral or bilateral signs: decreased distal limb position, vibration, or temperature sense or hyporeflexia; symptomatic PN (SPN) was defined as the presence of these signs with symptoms. Analysis used nonparametric statistics.
  
  
  RESULTS
  Overall, 20 (35%) of 58 antiretroviral-naive male subjects without diabetes evaluated at a median of 107 days post HIV transmission met criteria for PN. Thirteen (65%) of 20 PN subjects met criteria for SPN; 6 (30%) of 20 had bilateral findings. PN subjects and no PN subjects (NPN) did not differ in median age, days post HIV transmission, blood CD4 or CD8 counts, CSF or plasma HIV RNA levels, CSF white blood cell counts, or CSF to blood albumin ratio. PN and SPN subjects had elevated CSF neopterin (P = 0.003 and P = 0.0005), CSF monocyte chemoattractant protein-1 (P = 0.006 and P = 0.01), and blood neopterin (P = 0.006 and P = 0.009) compared with NPN subjects. PN subjects had a higher percentage of activated phenotype CSF CD8 T lymphocytes than NPN subjects (P = 0.009).
  
  
  CONCLUSIONS
  Signs of PN were detected by detailed neurologic examination in 35% of men enrolled in a neurological study at a median of 3.5 months after HIV transmission. PN during this early period may be mediated by systemic and nervous system immune responses to HIV.
authors.affiliation: *Department of Neurology, Yale University School of Medicine, New Haven, CT; †Department of Neurology, Harborview Medical Center, University of Washington Medical Center, Seattle, WA; ‡Department of Neurology, University of California San Francisco, San Francisco, CA; §Department of Neurology, University of North Carolina, Chapel Hill, NC; and ‖Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Austria.
authors.forename: Samantha X Y
authors.initials: SX
authors.lastname: Wang
authors.forename: Emily L
authors.initials: EL
authors.lastname: Ho
authors.forename: Marie
authors.initials: M
authors.lastname: Grill
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lee
authors.forename: Julia
authors.initials: J
authors.lastname: Peterson
authors.forename: Kevin
authors.initials: K
authors.lastname: Robertson
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.forename: Serena
authors.initials: S
authors.lastname: Spudich
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D054357:Chemokine CXCL10 / Q000097:blood / Q000134:cerebrospinal fluid; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications* / Q000276:immunology; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood / Q000134:cerebrospinal fluid; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000821:virology*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D012367:RNA, Viral; D019798:Neopterin
references.citation: Arch Neurol. 1995 Jan;52(1):45-51
references.pmid: 7826275
references.citation: Mol Med. 1997 Aug;3(8):553-64
references.pmid: 9307983
references.citation: Ann Neurol. 1997 Sep;42(3):368-72
references.pmid: 9307260
references.citation: J Infect Dis. 2011 Dec 15;204(12):1936-45
references.pmid: 22021620
references.citation: Neurol Clin. 2007 Feb;25(1):209-55
references.pmid: 17324726
references.citation: Neurology. 2010 Dec 7;75(23):2087-96
references.pmid: 21135382
references.citation: Neurology. 2007 Oct 30;69(18):1781-8
references.pmid: 17967994
references.citation: Proteomics Clin Appl. 2010 Mar;4(3):295-303
references.pmid: 21137050
references.citation: Lancet. 1986 Apr 12;1(8485):852
references.pmid: 2870330
references.citation: J Neuroimmunol. 2005 Nov;168(1-2):154-63
references.pmid: 16091292
references.citation: BMC Neurol. 2007 Apr 05;7:8
references.pmid: 17411437
references.citation: Drugs. 2000 Jun;59(6):1251-60
references.pmid: 10882161
references.citation: J Virol. 2008 Jun;82(11):5510-8
references.pmid: 18353964
references.citation: AIDS. 2002 Feb 15;16(3):407-12
references.pmid: 11834952
references.citation: J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):544-52
references.pmid: 18362693
references.citation: J Immunol. 1999 Sep 1;163(5):2953-9
references.pmid: 10453044
references.citation: AIDS. 2000 Oct 20;14(15):2333-9
references.pmid: 11089621
references.citation: Can J Neurol Sci. 2009 May;36(3):285-95
references.pmid: 19534327
references.citation: Clin Immunol Immunopathol. 1989 Jul;52(1):10-8
references.pmid: 2656013
references.citation: Clin Exp Immunol. 1992 Dec;90(3):376-82
references.pmid: 1458674
references.citation: Clin Med (Lond). 2011 Dec;11(6):571-5
references.pmid: 22268312
references.citation: Arch Neurol. 1993 Feb;50(2):167-71
references.pmid: 8381649
references.citation: AIDS Res Ther. 2010 Jun 03;7:15
references.pmid: 20525234
references.citation: J Neuroimmunol. 1999 Jan 1;93(1-2):172-81
references.pmid: 10378881
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13795-800
references.pmid: 12374865
references.citation: Acta Neuropathol. 1995;90(3):244-50
references.pmid: 8525797
references.citation: J Infect Dis. 2011 Sep 1;204(5):753-60
references.pmid: 21844301
references.citation: Am J Pathol. 2011 Nov;179(5):2337-45
references.pmid: 21924225
references.citation: J Neurosci. 2001 Jul 15;21(14):5027-35
references.pmid: 11438578
references.citation: AIDS. 1992 Aug;6(8):793-7
references.pmid: 1418775
references.citation: Mol Pain. 2011 May 20;7:40
references.pmid: 21599974
references.citation: J Peripher Nerv Syst. 2001 Mar;6(1):21-7
references.pmid: 11293804
references.citation: Neurology. 2002 Jun 25;58(12):1764-8
references.pmid: 12084874
references.citation: Scand J Infect Dis. 1986;18(6):591-2
references.pmid: 3468607
references.citation: Arch Neurol. 1994 Mar;51(3):236
references.pmid: 8129632
references.citation: Infect Dis Clin North Am. 2007 Mar;21(1):19-48, vii
references.pmid: 17502228
references.citation: Mol Pain. 2008 Mar 19;4:10
references.pmid: 18353190
references.citation: Ann Neurol. 1998 Nov;44(5):831-5
references.pmid: 9818943
references.citation: Clin Infect Dis. 2000 Jun;30(6):962-5
references.pmid: 10880317
references.citation: Res Virol. 1990 Jul-Aug;141(4):427-33
references.pmid: 2080315
references.citation: AIDS. 1998 Jul 30;12(11):1267-73
references.pmid: 9708405
references.citation: J Infect Dis. 2004 Jun 15;189(12):2202-12
references.pmid: 15181567
references.citation: J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Aug 1;18(4):332-40
references.pmid: 9704938
references.citation: J Neurol Sci. 1996 Mar;136(1-2):117-28
references.pmid: 8815158
references.citation: Ann Intern Med. 1987 Dec;107(6):849-51
references.pmid: 3688679
references.citation: AIDS. 2011 Apr 24;25(7):919-28
references.pmid: 21330902
references.citation: Neurology. 2004 Apr 27;62(8):1378-83
references.pmid: 15111677
references.citation: J Infect Dis. 2012 Jul 15;206(2):275-82
references.pmid: 22551810
references.citation: J Neurosci. 2011 Jul 27;31(30):10819-28
references.pmid: 21795534
references.citation: Neurology. 2005 Mar 8;64(5):842-8
references.pmid: 15753420
references.citation: Neurology. 1994 Jun;44(6):1120-30
references.pmid: 7516054
references.citation: J Neurosci. 2001 Apr 15;21(8):2808-19
references.pmid: 11306633
references.citation: Ann Neurol. 1988 May;23(5):485-92
references.pmid: 2839106
references.citation: J Neuroimmunol. 2001 May 1;116(1):29-39
references.pmid: 11311327
references.citation: Neurology. 1999 Feb;52(3):607-13
references.pmid: 10025796