title: Updates on clinically isolated syndrome and diagnostic criteria for multiple sclerosis.
abstract: Clinically isolated syndrome (CIS) is a central nervous system demyelinating event isolated in time that is compatible with the possible future development of multiple sclerosis (MS). Early risk stratification for conversion to MS helps with treatment decisions. Magnetic resonance imaging (MRI) is currently the most useful tool to evaluate risk. Cerebrospinal fluid studies and evoked potentials may also be used to assess the likelihood of MS. Four clinical trials evaluating the benefits of either interferon β (IFN-β) or glatiramer acetate (GA) within the first 3 months after a high-risk CIS demonstrate decreased rates of conversion to clinically definite MS (CDMS) and a lesser degree of MRI progression with early treatment. In the 3-, 5-, and 10-year extension studies of 2 formulations of IFN-β, the decreased conversion rate to CDMS remained meaningful when comparing early treatment of CIS to treatment delayed by a median of 2 to 3 years. Diagnostic criteria have been developed based on the clinical and MRI follow-up of large cohorts with CIS and provide guidance on how to utilize clinical activity in combination with radiographic information to diagnose MS. The most recent 2010 McDonald criteria simplify requirements for dissemination in time and space and allow for diagnosis of MS from a baseline brain MRI if there are both silent gadolinium-enhancing lesions and nonenhancing lesions on the same imaging study. The diagnostic criteria for MS require special consideration in children at risk for acute disseminated encephalomyelitis (ADEM), in older adults who may have small vessel ischemic disease, and in ethnic groups that more commonly develop neuromyelitis optica (NMO).
authors: Department of Neurology, University of California, San Francisco, CA, USA.
authors: Jacqueline F
authors: JF
authors: Marcus
authors: Emmanuelle L
authors: EL
authors: Waubant
keywords: autoimmune diseases of the nervous system; demyelinating diseases; imaging; multiple sclerosis; outcomes
references: Arch Neurol. 1987 Jan;44(1):21-3
references: 3800716
references: Brain. 1993 Feb;116 ( Pt 1):135-46
references: 8453454
references: Mult Scler. 2008 Sep;14(8):1026-30
references: 18632775
references: J Neurol. 2008 Aug;255(8):1159-63
references: 18446305
references: Neurology. 2008 Mar 25;70(13 Pt 2):1079-83
references: 17881717
references: Mult Scler. 2012 May;18(5):679-82
references: 22013145
references: Rev Neurol Dis. 2005 Summer;2(3):109-16
references: 16400309
references: Convuls Ther. 1996 Jun;12(2):104-7
references: 8744170
references: J Neurol Neurosurg Psychiatry. 1988 Dec;51(12):1569-71
references: 3221224
references: J Neurol. 2008 Oct;255(10):1449-63
references: 19005625
references: J Neurol. 2009 Jul;256(7):1061-6
references: 19252775
references: Int Rev Neurobiol. 2007;79:449-74
references: 17531854
references: Neurology. 2006 Sep 12;67(5):809-13
references: 16966542
references: Neurology. 2007 Jun 12;68(24 Suppl 4):S12-5
references: 17562845
references: Ann Neurol. 1983 Mar;13(3):227-31
references: 6847134
references: Neuroradiology. 2009 May;51(5):279-92
references: 19277621
references: J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1225-30
references: 12933923
references: AJNR Am J Neuroradiol. 2001 Aug;22(7):1362-7
references: 11498428
references: Ann Neurol. 2011 Jul;70(1):182-3
references: 21710623
references: Med Clin North Am. 2009 Mar;93(2):451-76, ix-x
references: 19272518
references: Mult Scler. 2009 Jul;15(7):887-8
references: 19542266
references: Cochrane Database Syst Rev. 2000;(4):CD001331
references: 11034713
references: Lancet. 2009 Oct 31;374(9700):1503-11
references: 19815268
references: Ann Neurol. 2010 Feb;67(2):159-69
references: 20225269
references: Brain. 1987 Dec;110 ( Pt 6):1579-616
references: 3427402
references: Arch Neurol. 2000 Jul;57(7):974-9
references: 10891979
references: J Neurol Neurosurg Psychiatry. 1998 May;64 Suppl 1:S2-5
references: 9647277
references: Neurology. 1999 Sep 22;53(5):1107-14
references: 10496275
references: J Neurol Neurosurg Psychiatry. 1996 May;60(5):572-5
references: 8778266
references: Curr Treat Options Neurol. 2010 May;12(3):244-55
references: 20842585
references: Lancet Neurol. 2005 May;4(5):281-8
references: 15847841
references: Phys Med Rehabil Clin N Am. 2005 May;16(2):383-409, viii
references: 15893678
references: Ann Neurol. 2005 Dec;58(6):840-6
references: 16283615
references: Neurology. 2003 Mar 11;60(5):848-53
references: 12629245
references: Brain. 2003 Oct;126(Pt 10):2279-90
references: 12847079
references: Lancet. 2001 May 19;357(9268):1576-82
references: 11377645
references: Neurology. 2006 Oct 10;67(7):1242-9
references: 16914693
references: Radiology. 1991 Jul;180(1):215-21
references: 2052698
references: Lancet. 2004 Oct 23-29;364(9444):1489-96
references: 15500893
references: J Child Neurol. 1997 Oct;12(7):448-54
references: 9373802
references: Neurology. 2002 Oct 22;59(8):1224-31
references: 12391351
references: Neurology. 2010 Oct 19;75(16):1423-7
references: 20826711
references: Arch Neurol. 2001 Dec;58(12):2044-5
references: 11735778
references: J Neuroophthalmol. 2009 Jun;29(2):104-6
references: 19491632
references: Brain. 1991 Dec;114 ( Pt 6):2437-50
references: 1782525
references: BMJ. 2006 Mar 4;332(7540):525-7
references: 16513709
references: Mult Scler. 2005 Aug;11(4):373-7
references: 16042216
references: Brain. 2007 May;130(Pt 5):1235-43
references: 17449477
references: J Neurol. 2003 Dec;250(12):1447-52
references: 14673577
references: Neuroradiology. 1988;30(4):299-302
references: 3050587
references: Arq Neuropsiquiatr. 2008 Mar;66(1):120-38
references: 18392436
references: J Clin Neuromuscul Dis. 2008 Dec;10(2):52-5
references: 19169090
references: Ann Neurol. 2011 Feb;69(2):292-302
references: 21387374
references: Neurology. 1998 Aug;51(2):529-34
references: 9710030
references: Ann Neurol. 1999 Dec;46(6):878-86
references: 10589540
references: N Engl J Med. 2002 Jan 17;346(3):158-64
references: 11796849
references: Ann Neurol. 2000 Jun;47(6):831-5
references: 10852554
references: Neurology. 2004 Nov 23;63(10):1966-7
references: 15557527
references: Arch Ophthalmol. 2003 Jul;121(7):944-9
references: 12860795
references: AJNR Am J Neuroradiol. 1995 Feb;16(2):259-64
references: 7726070
references: Ann Neurol. 2008 Dec;64(6):707-13
references: 19107998
references: Neuroradiology. 1996 May;38(4):317-21
references: 8738086
references: Ann Neurol. 2001 Jul;50(1):121-7
references: 11456302
references: J Pediatr. 2004 Feb;144(2):246-52
references: 14760270
references: Int MS J. 2007 Mar;14(1):29-34
references: 17509251
references: Neurology. 1988 Oct;38(10):1511-5
references: 3419593
references: J Pediatr. 2006 Jul;149(1):125-7
references: 16860140
references: Neurology. 2002 Jan 8;58(1):143-6
references: 11781423
references: J Clin Endocrinol Metab. 2004 Oct;89(10):4923-8
references: 15472186
references: Brain. 2007 May;130(Pt 5):1206-23
references: 17439988
references: Lancet Neurol. 2009 Nov;8(11):987-97
references: 19748319
references: J Neurol Neurosurg Psychiatry. 1988 Feb;51(2):285-7
references: 3346696
references: Neurology. 2009 Sep 22;73(12):941-8
references: 19641168
references: Neuroradiology. 1994 Jul;36(5):382-7
references: 7936181
references: Lancet Neurol. 2007 Sep;6(9):805-15
references: 17706564
references: Neurology. 2003 Feb 25;60(4):721-2
references: 12601124
references: Med Clin North Am. 2003 Jul;87(4):867-97, viii-ix
references: 12834152
references: Lancet Neurol. 2007 Aug;6(8):677-86
references: 17616439
references: Ann N Y Acad Sci. 1965 Mar 31;122:552-68
references: 14313512
references: Neurology. 2007 Apr 17;68(16 Suppl 2):S23-36
references: 17438235
references: Ann Neurol. 1993 Jan;33(1):18-27
references: 8494332
references: Mult Scler. 2008 Jun;14(5):631-5
references: 18566026
references: Radiology. 1987 Feb;162(2):509-11
references: 3797666
references: Mult Scler. 2003 Feb;9(1):39-43
references: 12617267
references: Mult Scler. 2001 Dec;7(6):359-63
references: 11795456
references: Lancet. 1997 Mar 29;349(9056):902-6
references: 9093250
references: Ann Neurol. 2002 Jul;52(1):47-53
references: 12112046
references: Curr Treat Options Neurol. 2009 May;11(3):203-10
references: 19364455
references: Neurology. 2009 Mar 3;72(9):800-5
references: 19073949
references: Neurology. 2007 Apr 17;68(16 Suppl 2):S54-65
references: 17438239
references: Brain. 2004 May;127(Pt 5):1101-7
references: 14998914
references: Brain. 1998 Mar;121 ( Pt 3):495-503
references: 9549525
references: AJNR Am J Neuroradiol. 2007 Feb;28(2):262-6
references: 17296991
references: Neurology. 2004 Dec 14;63(11):2028-33
references: 15596745
references: J Neurol Neurosurg Psychiatry. 2006 Jul;77(7):830-3
references: 16043456
references: J Neurol. 1999 Sep;246(9):770-5
references: 10525973
references: Neurol Sci. 2004 Nov;25 Suppl 4:S361-3
references: 15727234
references: AJNR Am J Neuroradiol. 2007 Oct;28(9):1645-9
references: 17885241
references: J Neuroimmunol. 2010 Feb 26;219(1-2):1-7
references: 19782408
references: Lancet Neurol. 2007 Oct;6(10):887-902
references: 17884679
references: Neurologist. 2009 Jan;15(1):1-5
references: 19131851
references: Mult Scler. 2010 Jan;16(1):55-61
references: 19995838
references: Arch Neurol. 1991 Oct;48(10):1086-8
references: 1929904
references: AJNR Am J Neuroradiol. 2000 Apr;21(4):702-6
references: 10782781
references: Neurology. 1988 Dec;38(12):1822-5
references: 3057397
references: Cleve Clin J Med. 2006 Jan;73(1):91-102
references: 16444920
references: Annu Rev Neurosci. 2008;31:247-69
references: 18558855
references: Neurology. 2006 May 23;66(10):1485-9
references: 16717206
references: Nervenarzt. 2006 Apr;77(4):430-8
references: 16341736
references: Mult Scler. 2009 Feb;15(2):159-73
references: 18987106
references: Wien Med Wochenschr. 1986 Sep 30;136(18):477-80
references: 2948324
references: AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1034-8
references: 10871009
references: Eur J Radiol. 2008 Sep;67(3):409-14
references: 18434066
references: Lancet. 2007 Aug 4;370(9585):389-97
references: 17679016
references: Neurology. 2006 Feb 28;66(4):576-8
references: 16505315
references: Arch Ophthalmol. 1988 Aug;106(8):1051-3
references: 3041942
references: J Neurol. 2008 Apr;255(4):480-7
references: 18004635
references: Mult Scler. 2009 Apr;15(4):472-8
references: 19153171
references: Arch Neurol. 2007 Oct;64(10):1416-22
references: 17923625
references: Clin Neurol Neurosurg. 2006 Mar;108(3):271-4
references: 16378679
references: Neurol Sci. 2009 Oct;30(5):421-30
references: 19609739
references: Mt Sinai J Med. 2008 Mar-Apr;75(2):157-67
references: 18500719
references: Brain. 2004 Sep;127(Pt 9):1942-7
references: 15289266
references: Brain. 2000 Dec;123 Pt 12:2407-22
references: 11099444
references: Arch Neurol. 2005 Jun;62(6):865-70
references: 15956157
references: N Engl J Med. 2011 Dec 8;365(23):2188-97
references: 22150037
references: Neurology. 2010 Feb 2;74(5):399-405
references: 20124205
references: Neurology. 2007 Apr 17;68(16 Suppl 2):S70-4
references: 17438242
references: J Neurol. 2000 Jun;247(6):435-42
references: 10929272
references: Arch Neurol. 2006 Apr;63(4):614-9
references: 16606781
references: Arch Neurol. 2004 Feb;61(2):217-21
references: 14967769
references: Arch Ophthalmol. 2008 Jul;126(7):994-5
references: 18625951
references: Mult Scler. 2008 Nov;14(9):1157-74
references: 18805839
references: Neurology. 1999 Sep 11;53(4):679-86
references: 10489026
references: Brain. 2008 Jul;131(Pt 7):1759-75
references: 18535080
references: Neurology. 2007 Apr 17;68(16 Suppl 2):S7-12
references: 17438241
references: Neurology. 2010 Feb 2;74(5):427-34
references: 20054006
references: Neuropediatrics. 2004 Apr;35(2):143-6
references: 15127316
references: Neurology. 2006 Mar 14;66(5):678-84
references: 16436649
references: Mult Scler. 1998 Oct;4(5):408-12
references: 9839300
references: Arch Neurol. 1982 Jun;39(6):350-4
references: 7092611
references: Arch Intern Med. 1994 Jan 10;154(1):97-101
references: 8267494
references: Neurology. 2010 Nov 30;75(22):1988-94
references: 21115953
references: J Neuroimmunol. 2006 Nov;180(1-2):17-28
references: 16945427
references: AJNR Am J Neuroradiol. 2006 Feb;27(2):455-61
references: 16484429
references: Neurology. 2003 Sep 9;61(5):602-11
references: 12963748
references: N Engl J Med. 1992 Feb 27;326(9):581-8
references: 1734247
references: J Neurol Neurosurg Psychiatry. 1993 Nov;56(11):1219-20
references: 8229035
references: Ann Neurol. 1989 Jan;25(1):43-9
references: 2913928
references: J Neurol. 2000 Dec;247(12):977-9
references: 11200696
references: Pediatrics. 1986 Jan;77(1):107-12
references: 3940347
references: Arch Neurol. 2009 May;66(5):587-92
references: 19433658
references: NeuroRx. 2005 Apr;2(2):277-303
references: 15897951
references: Arch Neurol. 2012 Feb;69(2):183-90
references: 21987393
references: Brain. 2003 Feb;126(Pt 2):276-84
references: 12538397
references: Neurology. 2008 Sep 30;71(14):1090-3
references: 18824673
references: Lancet. 1988 Nov 19;2(8621):1202-3
references: 2903418
references: Int MS J. 2007 Jun;14(2):58-63
references: 17686345
references: Arch Neurol. 2008 Aug;65(8):1044-51
references: 18541787
references: Brain. 1997 Nov;120 ( Pt 11):2059-69
references: 9397021
references: Klin Wochenschr. 1990 Dec 4;68(23):1183-8
references: 2280582
references: Semin Neurol. 1986 Mar;6(1):24-32
references: 3503355
references: Neurology. 2003 Jan 14;60(1):27-30
references: 12525713
references: J Clin Apher. 1994;9(1):1-5
references: 8195107
references: Lancet Neurol. 2007 Sep;6(9):773-81
references: 17689148
references: N Engl J Med. 2000 Sep 28;343(13):898-904
references: 11006365
references: Neurology. 1988 Feb;38(2):180-5
references: 3340277
references: Radiology. 2002 Apr;223(1):46-56
references: 11930047
references: Mult Scler. 2005 Aug;11(4):390-4
references: 16042219