Top

Published in:

01-10-2010 | Review

The radiologically isolated syndrome: take action when the unexpected is uncovered?

Authors: Johann Sellner, Lucas Schirmer, Bernhard Hemmer, Mark Mühlau

Published in: Journal of Neurology | Issue 10/2010

Abstract

The increasing diagnostic application of magnetic resonance imaging (MRI) in neurology has resulted in an increase in accidental disclosure of asymptomatic brain pathologies with potential clinical significance. Here, we discuss the incidental detection of multiple sclerosis (MS) typical central nervous system (CNS) lesions fulfilling MRI criteria for dissemination in space (radiologically isolated syndrome, RIS) and its diagnostic, prognostic and therapeutic implications. Three recent studies, including a total of 136 RIS cases which were followed for up to 10 years, indicate that a subgroup of such patients will develop MS. MRI-based dissemination in time (DIT) was determined in more than two-thirds and clinically isolated syndrome (CIS) occurred in almost one-third of the patients. Presence of Gadolinium (Gd)-enhancing lesions was identified as potential predictor for MRI-based DIT in one study, and pathological visual evoked potential (VEP) examinations at baseline and Gd-enhancement at the second MRI scan for CIS (clinical DIT) in another study. In the lack of established management guidelines, we propose a pragmatic diagnostic and therapeutic approach for patients with RIS. Individual concepts are required and both “wait” as well as “follow” strategies are justifiable. Further prospective studies are required to elucidate potential biomarkers for narrowing down the high-risk cohort and exploring further characteristics of this disease stage.

Barkhof F, Filippi M, Miller DH, Scheltens P, Campi A, Polman CH, Comi G, Ader HJ, Losseff N, Valk J (1997) Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 120:2059–2069CrossRefPubMed

Benedict RH, Fazekas F (2009) Benign or not benign MS. A role for routine neuropsychological assessment? Neurology 73:494–495CrossRefPubMed

Bot JC, Barkhof F, Polman CH, Lycklama a Nijeholt GJ, de Groot V, Bergers E, Ader HJ, Castelijns JA (2004) Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. Neurology 62:226–233PubMed

Bourdette D, Simon J (2009) The radiologically isolated syndrome: is it very early multiple sclerosis? Neurology 72:780–781CrossRefPubMed

Brex PA, Miszkiel KA, O’Riordan JI, Plant GT, Moseley IF, Thompson AJ, Miller DH (2001) Assessing the risk of early multiple sclerosis in patients with clinically isolated syndromes: the role of a follow up MRI. J Neurol Neurosurg Psychiatry 70:390–393CrossRefPubMed

Butler MA, Bennett TL (2003) In search of a conceptualization of multiple sclerosis: a historical perspective. Neuropsychol Rev 13:93–112CrossRefPubMed

Castaigne P, Lhermitte F, Escourolle R, Hauw JJ, Gray F, Lyon-Caen O (1981) Les scleroses en plaques asymptomatiques. Rev Neurol (Paris) 137:729–739

Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernandez O, Hartung H, Seeldrayers P, Sorensen PS, Rovaris M, Martinelli V, Hommes OR (2001) Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357:1576–1582CrossRefPubMed

Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517CrossRefPubMed

10.

Confavreux C, Vukusic S (2008) The clinical epidemiology of multiple sclerosis. Neuroimaging Clin N Am 18:589–622CrossRefPubMed

11.

Engell T (1989) A clinical patho-anatomical study of clinically silent multiple sclerosis. Acta Neurol Scand 79:428–430CrossRefPubMed

12.

Ergun U, Ozer G, Sekercan S, Artan E, Kudiaki C, Ucler S, Coskun O, Inan L (2009) Headaches in the different phases of relapsing-remitting multiple sclerosis: a tendency for stabbing headaches during relapses. Neurologist 15:212–216CrossRefPubMed

13.

Feuillet L, Reuter F, Audoin B, Malikova I, Barrau K, Cherif AA, Pelletier J (2007) Early cognitive impairment in patients with clinically isolated syndrome suggestive of multiple sclerosis. Mult Scler 13:124–127CrossRefPubMed

14.

Fisniku LK, Brex PA, Altmann DR, Miszkiel KA, Benton CE, Lanyon R, Thompson AJ, Miller DH (2008) Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 131:808–817CrossRefPubMed

15.

Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H (2009) The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 132:1175–1189CrossRefPubMed

16.

Gilbert JJ, Sadler M (1983) Unsuspected multiple sclerosis. Arch Neurol 40:533–536PubMed

17.

Hakiki B, Goretti B, Portaccio E, Zipoli V, Amato MP (2008) ‘Subclinical MS’: follow-up of four cases. Eur J Neurol 15:858–861CrossRefPubMed

18.

Hemmer B, Nessler S, Zhou D, Kieseier B, Hartung HP (2006) Immunopathogenesis and immunotherapy of multiple sclerosis. Nat Clin Pract Neurol 2:201–211CrossRefPubMed

19.

Hutchinson M (2009) Predicting and preventing the future: actively managing multiple sclerosis. Pract Neurol 9:133–143, (discussion 144)

20.

Jacobi C, Hahnel S, Martinez-Torres F, Rieger S, Juttler E, Heiland S, Jarius S, Meyding-Lamade U, Storch-Hagenlocher B, Wildemann B (2008) Prospective combined brain and spinal cord MRI in clinically isolated syndromes and possible early multiple sclerosis: impact on dissemination in space and time. Eur J Neurol 15:1359–1364CrossRefPubMed

21.

Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownscheidle CM, Murray TJ, Simonian NA, Slasor PJ, Sandrock AW (2000) Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 343:898–904CrossRefPubMed

22.

Kappos L, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Radu EW, Metzig C, Bauer L, Lanius V, Sandbrink R, Pohl C (2009) Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol 8:987–997CrossRefPubMed

23.

Kobelt G, Berg J, Lindgren P, Kerrigan J, Russell N, Nixon R (2006) Costs and quality of life of multiple sclerosis in the United Kingdom. Eur J Health Econ 7 S2:S96–104

24.

Kurne A, Isikay IC, Karlioguz K, Kalyoncu U, Aydin OF, Calguneri M, Karabudak R (2008) A clinically isolated syndrome: a challenging entity: multiple sclerosis or collagen tissue disorders: clues for differentiation. J Neurol 255:1625–1635CrossRefPubMed

25.

Lebrun C, Bensa C, Debouverie M, De Seze J, Wiertlievski S, Brochet B, Clavelou P, Brassat D, Labauge P, Roullet E (2008) Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile. J Neurol Neurosurg Psychiatry 79:195–198CrossRefPubMed

26.

Lebrun C, Bensa C, Debouverie M, Wiertlevski S, Brassat D, de Seze J, Rumbach L, Pelletier J, Labauge P, Brochet B, Tourbah A, Clavelou P (2009) Association between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: follow-up of 70 patients. Arch Neurol 66:841–846CrossRefPubMed

27.

Lyoo IK, Seol HY, Byun HS, Renshaw PF (1996) Unsuspected multiple sclerosis in patients with psychiatric disorders: a magnetic resonance imaging study. J Neuropsychiatry Clin Neurosci 8:54–59PubMed

28.

McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127CrossRefPubMed

29.

Miller D, Barkhof F, Montalban X, Thompson A, Filippi M (2005) Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 4:281–288CrossRefPubMed

30.

Miller D, McDonald I, Smith K (2006) The diagnosis of multiple sclerosis. In: Compston A (ed) McAlpine’s multiple sclerosis. Churchill Livingstone Elsevier, Cambridge, pp 347–388

31.

Miller DH, Weinshenker BG, Filippi M, Banwell BL, Cohen JA, Freedman MS, Galetta SL, Hutchinson M, Johnson RT, Kappos L, Kira J, Lublin FD, McFarland HF, Montalban X, Panitch H, Richert JR, Reingold SC, Polman CH (2008) Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler 14:1157–1174CrossRefPubMed

32.

Morris Z, Whiteley WN, Longstreth WT Jr, Weber F, Lee YC, Tsushima Y, Alphs H, Ladd SC, Warlow C, Wardlaw JM, Al-Shahi Salman R (2009) Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 339:b3016CrossRefPubMed

33.

Mowry EM, Pesic M, Grimes B, Deen S, Bacchetti P, Waubant E (2009) Demyelinating events in early multiple sclerosis have inherent severity and recovery. Neurology 72:602–608CrossRefPubMed

34.

Neema M, Goldberg-Zimring D, Guss ZD, Healy BC, Guttmann CR, Houtchens MK, Weiner HL, Horsfield MA, Hackney DB, Alsop DC, Bakshi R (2009) 3 T MRI relaxometry detects T2 prolongation in the cerebral normal-appearing white matter in multiple sclerosis. Neuroimage 46:633–641CrossRefPubMed

35.

Okuda DT (2009) Unanticipated demyelinating pathology of the CNS. Nat Rev Neurol 5:591–597CrossRefPubMed

36.

Okuda DT, Mowry EM, Beheshtian A, Waubant E, Baranzini SE, Goodin DS, Hauser SL, Pelletier D (2009) Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 72:800–805CrossRefPubMed

37.

Pittock SJ, McClelland RL, Mayr WT, Jorgensen NW, Weinshenker BG, Noseworthy J, Rodriguez M (2004) Clinical implications of benign multiple sclerosis: a 20-year population-based follow-up study. Ann Neurol 56:303–306CrossRefPubMed

38.

Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846CrossRefPubMed

39.

Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231CrossRefPubMed

40.

Putzki N, Pfriem A, Limmroth V, Yaldizli O, Tettenborn B, Diener HC, Katsarava Z (2009) Prevalence of migraine, tension-type headache and trigeminal neuralgia in multiple sclerosis. Eur J Neurol 16:262–267CrossRefPubMed

41.

Ranjeva JP, Audoin B, Au Duong MV, Confort-Gouny S, Malikova I, Viout P, Soulier E, Pelletier J, Cozzone PJ (2006) Structural and functional surrogates of cognitive impairment at the very early stage of multiple sclerosis. J Neurol Sci 245:161–167CrossRefPubMed

42.

Rocca MA, Ceccarelli A, Falini A, Colombo B, Tortorella P, Bernasconi L, Comi G, Scotti G, Filippi M (2006) Brain gray matter changes in migraine patients with T2-visible lesions: a 3-T MRI study. Stroke 37:1765–1770CrossRefPubMed

43.

Schirmer L, Albert M, Buss A, Schulz-Schaeffer WJ, Antel JP, Brück W, Stadelmann C (2009) Substantial early, but non-progressive neuronal loss in MS spinal cord. Ann Neurol 66:698–704CrossRefPubMed

44.

Sellner J, Greeve I, Findling O, Kamm CP, Minten C, Engelhardt B, Grandgirard D, Leib SL, Mattle HP (2008) Effect of interferon-beta and atorvastatin on Th1/Th2 cytokines in multiple sclerosis. Neurochem Int 53:17–21CrossRefPubMed

45.

Sellner J, Greeve I, Leib SL, Mattle HP (2008) Atorvastatin does not alter interferon Beta-induced changes of serum matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in patients with multiple sclerosis. Arch Neurol 65:672–674CrossRefPubMed

46.

Simioni S, Ruffieux C, Bruggimann L, Annoni JM, Schluep M (2007) Cognition, mood and fatigue in patients in the early stage of multiple sclerosis. Swiss Med Wkly 137:496–501PubMed

47.

Siva A, Saip S, Altintas A, Jacob A, Keegan B, Kantarci O (2009) Multiple sclerosis risk in radiologically uncovered asymptomatic possible inflammatory-demyelinating disease. Mult Scler 15:918–927CrossRefPubMed

48.

Thrower BW (2007) Clinically isolated syndromes: predicting and delaying multiple sclerosis. Neurology 68:S12–S15CrossRefPubMed

49.

Tienari PJ, Salonen O, Wikstrom J, Valanne L, Palo J (1992) Familial multiple sclerosis: MRI findings in clinically affected and unaffected siblings. J Neurol Neurosurg Psychiatry 55:883–886CrossRefPubMed

50.

Tintore M (2008) Rationale for early intervention with immunomodulatory treatments. J Neurol 255 (Suppl 1):37–43

51.

Tintore M, Rovira A, Martinez MJ, Rio J, Diaz-Villoslada P, Brieva L, Borras C, Grive E, Capellades J, Montalban X (2000) Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. AJNR Am J Neuroradiol 21:702–706PubMed

52.

Tintore M, Rovira A, Rio J, Nos C, Grive E, Sastre-Garriga J, Pericot I, Sanchez E, Comabella M, Montalban X (2003) New diagnostic criteria for multiple sclerosis: application in first demyelinating episode. Neurology 60:27–30PubMed

53.

Tintore M, Rovira A, Rio J, Nos C, Grive E, Tellez N, Pelayo R, Comabella M, Sastre-Garriga J, Montalban X (2006) Baseline MRI predicts future attacks and disability in clinically isolated syndromes. Neurology 67:968–972CrossRefPubMed

54.

Tintore M, Rovira A, Rio J, Tur C, Pelayo R, Nos C, Tellez N, Perkal H, Comabella M, Sastre-Garriga J, Montalban X (2008) Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis? Neurology 70:1079–1083CrossRefPubMed

55.

Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285CrossRefPubMed

56.

Weiner HL (2009) The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease? Ann Neurol 65:239–248CrossRefPubMed

Title: The radiologically isolated syndrome: take action when the unexpected is uncovered?
Authors: Johann Sellner
Lucas Schirmer
Bernhard Hemmer
Mark Mühlau
Publication date: 01-10-2010
Publisher: Springer-Verlag
Published in: Journal of Neurology / Issue 10/2010
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-010-5601-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The radiologically isolated syndrome: take action when the unexpected is uncovered?

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2010

Clinical progression in Charcot–Marie-Tooth disease type 1A duplication: clinico-electrophysiological and MRI longitudinal study of a family

Obituary

Homozygosity for c 6325T>G transition in the ATM gene causes an atypical, late-onset variant form of ataxia-telangiectasia

Abnormalities of cerebral arteries are frequent in patients with late-onset Pompe disease

4H syndrome: a rare cause of leukodystrophy

Effects of exercise induced oxidative stress on glutathione levels in Parkinson’s disease on and off medication