The role of infections in the pathogenesis and course of multiple sclerosis.
Interplay between susceptibility genes and environmental factors is considered important player in the genesis of multiple sclerosis (MS). Among environmental factors, a role for an infectious pathogen has long been considered central to the disease process. This opinion has support both from epidemiological data and the findings of immunological abnormalities in spinal fluid that reflect an immune response to an as yet undetermined antigen, possibly a pathogen, in the cerebrospinal fluid. Our review will outline the current understanding of the role of infection in the causation and progression of MS. We will review the data that point to an infectious cause of MS and consider the specific agents Chlamydophila (Chlamydia) pneumoniae, Human Herpes Virus 6, and Epstein-Barr Virus, that are implicated in either the development or progression of MS.
Pawate
Siddharama
S
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. siddharama.pawate@vanderbilt.edu
Sriram
Subramaniam
S
Acta Neuropathol. 2001 Jun;101(6):601-4
11515789
Neurol India. 1999 Mar;47(1):18-21
10339703
J Neurol Sci. 2006 Jun 15;245(1-2):123-6
16650874
Clin Microbiol Rev. 2004 Jan;17(1):174-207
14726460
J Neurol Neurosurg Psychiatry. 1994 Aug;57(8):975-6
7520057
Neurology. 1982 Feb;32(2):143-50
6976526
Mayo Clin Proc. 1999 Feb;74(2):163-70
10069356
Arch Neurol. 2005 Sep;62(9):1345-56
16157741
Neurology. 1989 Dec;39(12):1566-72
2586770
Ann Neurol. 2005 Dec;58(6):939-45
16315280
Ann Acad Med Singap. 1985 Jan;14(1):32-6
4004124
Neurology. 1999 Oct 12;53(6):1367-8
10522909
Brain. 2007 Nov;130(Pt 11):2800-15
17956913
J Clin Epidemiol. 2001 Jan;54(1):1-22
11165464
Acta Neurol Scand Suppl. 2006;183:48-50
16637929
Ann Neurol. 1982 Jan;11(1):35-40
7036846
Mult Scler. 2006 Aug;12(4):397-411
16900753
J Physiol Pharmacol. 2006 Sep;57 Suppl 3:29-50
17033104
J Infect Dis. 2003 May 1;187(9):1377-87
12717618
Neurology. 1998 Feb;50(2):571-2
9484408
J Neurol Neurosurg Psychiatry. 1966 Feb;29(1):60-8
5910580
Ann Neurol. 1994 Dec;36 Suppl 2:S180-93
7998787
Clin Microbiol Rev. 2006 Jan;19(1):80-94
16418524
Neurology. 2000 Jul 25;55(2):178-84
10908887
Clin Sci (Lond). 2008 Apr;114(8):509-31
18336368
J Exp Med. 2007 Nov 26;204(12):2899-912
17984305
Neurology. 2001 Aug 28;57(4):746
11524506
Neurology. 2000 Jan 11;54(1):265
10636169
Lancet. 2008 Oct 25;372(9648):1502-17
18970977
Nat Med. 1997 Dec;3(12):1394-7
9396611
Neuroepidemiology. 1988;7(4):168-80
3194042
N Engl J Med. 2006 Mar 2;354(9):942-55
16510748
Int MS J. 2003 Apr;10(1):22-8
12906767
Ann N Y Acad Sci. 2007 Jun;1108:567-77
17894021
Ann Neurol. 2004 Apr;55(4):458-68
15048884
Lancet Neurol. 2008 Mar;7(3):268-77
18275928
Neurology. 2006 Aug 22;67(4):652-9
16870812
Lancet Neurol. 2006 Apr;5(4):343-54
16545751
Brain. 2008 Jul;131(Pt 7):1712-21
18550621
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7583-8
9207135
Eur J Neurol. 2006 Jul;13(7):700-22
16834700
J Neurovirol. 1995 Sep;1(3-4):253-8
9222363
Clin Microbiol Rev. 1993 Oct;6(4):382-427
8269393
Mult Scler. 2002 Aug;8(4):289-94
12166498
Neurology. 1989 Dec;39(12):1637-9
2586781
Rev Med Virol. 2005 May-Jun;15(3):179-211
15782388
Brain. 2000 May;123 ( Pt 5):968-74
10775541
Ann Neurol. 2007 Jun;61(6):514-23
17455291
Lancet Infect Dis. 2007 Apr;7(4):266-81
17376384
Ann Neurol. 2000 Jun;47(6):707-17
10852536
Ann Neurol. 2007 Apr;61(4):288-99
17444504
Brain. 2005 Jul;128(Pt 7):1649-66
15872019
Semin Neurol. 2007 Feb;27(1):78-85
17226744
Neurology. 2003 Nov 25;61(10):1373-7
14638958
Acta Neurol Scand. 1998 Nov;98(5):302-9
9858098
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7440-4
7638210
Scand J Immunol. 1993 Mar;37(3):369-76
8441923
Am J Phys Med Rehabil. 1995 Nov-Dec;74(6):415-8
8534384
Pediatr Rev. 2005 Mar;26(3):79-85
15743754
Curr Opin Neurol. 2001 Jun;14(3):355-9
11371760
Lancet. 2002 Apr 6;359(9313):1221-31
11955556
Lancet Neurol. 2007 Oct;6(10):903-12
17884680
Neurol Clin. 2005 Feb;23(1):107-29, vi-vii
15661090
Brain. 1988 Feb;111 ( Pt 1):1-25
3365543
Neurol India. 1999 Mar;47(1):8-11
10339701
J Med Virol. 2002 Mar;66(3):394-9
11793393
N Engl J Med. 1994 Aug 18;331(7):432-8
8035839
Ann Neurol. 1999 Jul;46(1):6-14
10401775
Lancet. 1985 Jun 8;1(8441):1313-5
2860501
Ann Neurol. 1994 Dec;36 Suppl 2:S231-43
7998792
Neurol Clin. 2008 Aug;26(3):657-74, viii
18657720
Neurol Clin. 2008 Aug;26(3):833-54, x-xi
18657729
Neurol Clin. 1999 Nov;17(4):783-800
10517928
J Neurovirol. 2000 May;6 Suppl 2:S134-40
10871801
J Neurol. 1993 Jul;240(7):417-22
8410082
Lancet Neurol. 2006 Nov;5(11):932-6
17052660
Int Rev Neurobiol. 2007;79:341-56
17531849
J Neurol Neurosurg Psychiatry. 2009 Jun;80(6):620-5
19168469
QJM. 2006 Sep;99(9):609-23
16905752
Neurology. 1976 Jun;26(6 PT 2):14-7
944886
J Neurol Sci. 2003 Feb 15;206(2):153-5
12559503
Brain. 2002 May;125(Pt 5):952-60
11960885
Neuroepidemiology. 1993;12(1):1-5
8327018
Brain Res Bull. 2003 Aug 15;61(3):321-6
12909302
Acta Neurol Scand. 2002 Aug;106(2):63-83
12100366