Clinically isolated syndromes suggestive of multiple sclerosis
- Michael J Olek, DO
Michael J Olek, DO
- Associate Professor of Neurology
- Loma Linda University Medical Center
INTRODUCTION AND DEFINITION
A clinically isolated syndrome (CIS) is a single attack compatible with multiple sclerosis, such as optic neuritis. An episode of CIS can create diagnostic and therapeutic dilemmas, since a substantial percentage of patients with CIS and MRI lesions go on to develop multiple sclerosis. Identifying those likely to develop multiple sclerosis may have particular importance, since accumulating evidence suggests that starting disease modifying therapies for patients with CIS can delay conversion to clinically definite multiple sclerosis.
A radiologically isolated syndrome (RIS) suggestive of multiple sclerosis is defined as a presentation without overt clinical symptoms but with MRI findings highly suggestive of multiple sclerosis based upon location and morphology within the central nervous system .
This topic will discuss the evaluation and treatment of CIS and RIS suggestive of multiple sclerosis.
Optic neuritis and other aspects of multiple sclerosis are discussed separately. (See "Diagnosis of multiple sclerosis in adults" and "Clinical features of multiple sclerosis in adults" and "Disease-modifying treatment of relapsing-remitting multiple sclerosis in adults" and "Treatment of progressive multiple sclerosis in adults" and "Symptom management of multiple sclerosis in adults" and "Optic neuritis: Pathophysiology, clinical features, and diagnosis" and "Optic neuritis: Prognosis and treatment".)
The typical patient with a clinically isolated syndrome (CIS) presents as a young adult with a single episode of central nervous system dysfunction followed by at least partial resolution. In contrast, a radiologically isolated syndrome (RIS) is defined by incidental MRI findings highly suggestive of multiple sclerosis in an asymptomatic patient lacking any history, symptoms, or signs of multiple sclerosis.
- Okuda DT, Mowry EM, Beheshtian A, et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 2009; 72:800.
- Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000; 343:1430.
- Miller DH, Chard DT, Ciccarelli O. Clinically isolated syndromes. Lancet Neurol 2012; 11:157.
- Barkhof F, Filippi M, Miller DH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997; 120 ( Pt 11):2059.
- Giorgio A, Stromillo ML, Rossi F, et al. Cortical lesions in radiologically isolated syndrome. Neurology 2011; 77:1896.
- Brex PA, Ciccarelli O, O'Riordan JI, et al. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 2002; 346:158.
- Frohman EM, Goodin DS, Calabresi PA, et al. The utility of MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003; 61:602.
- Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol 2008; 65:727.
- Fisniku LK, Brex PA, Altmann DR, et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008; 131:808.
- Tintoré M, Rovira A, Río J, et al. Baseline MRI predicts future attacks and disability in clinically isolated syndromes. Neurology 2006; 67:968.
- Okuda DT, Siva A, Kantarci O, et al. Radiologically isolated syndrome: 5-year risk for an initial clinical event. PLoS One 2014; 9:e90509.
- Kantarci OH, Lebrun C, Siva A, et al. Primary Progressive Multiple Sclerosis Evolving From Radiologically Isolated Syndrome. Ann Neurol 2016; 79:288.
- Optic Neuritis Study Group. The 5-year risk of MS after optic neuritis. Experience of the optic neuritis treatment trial. Neurology 1997; 49:1404.
- Beck RW, Trobe JD, Moke PS, et al. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial. Arch Ophthalmol 2003; 121:944.
- Bruna J, Martínez-Yélamos S, Martínez-Yélamos A, et al. Idiopathic acute transverse myelitis: a clinical study and prognostic markers in 45 cases. Mult Scler 2006; 12:169.
- Gajofatto A, Monaco S, Fiorini M, et al. Assessment of outcome predictors in first-episode acute myelitis: a retrospective study of 53 cases. Arch Neurol 2010; 67:724.
- Morrissey SP, Miller DH, Kendall BE, et al. The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis. A 5-year follow-up study. Brain 1993; 116 ( Pt 1):135.
- Ford B, Tampieri D, Francis G. Long-term follow-up of acute partial transverse myelopathy. Neurology 1992; 42:250.
- Scott TF, Kassab SL, Singh S. Acute partial transverse myelitis with normal cerebral magnetic resonance imaging: transition rate to clinically definite multiple sclerosis. Mult Scler 2005; 11:373.
- Bashir K, Whitaker JN. Importance of paraclinical and CSF studies in the diagnosis of MS in patients presenting with partial cervical transverse myelopathy and negative cranial MRI. Mult Scler 2000; 6:312.
- Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69:292.
- Montalban X, Tintoré M, Swanton J, et al. MRI criteria for MS in patients with clinically isolated syndromes. Neurology 2010; 74:427.
- Tintore M, Rovira À, Río J, et al. Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain 2015; 138:1863.
- Sombekke MH, Wattjes MP, Balk LJ, et al. Spinal cord lesions in patients with clinically isolated syndrome: a powerful tool in diagnosis and prognosis. Neurology 2013; 80:69.
- Miller DH, Filippi M, Fazekas F, et al. Role of magnetic resonance imaging within diagnostic criteria for multiple sclerosis. Ann Neurol 2004; 56:273.
- Tintoré M, Rovira A, Río J, et al. Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis? Neurology 2008; 70:1079.
- Bourdette D, Simon J. The radiologically isolated syndrome: is it very early multiple sclerosis? Neurology 2009; 72:780.
- Jacobs LD, Beck RW, Simon JH, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000; 343:898.
- Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001; 357:1576.
- Filippi M, Rovaris M, Inglese M, et al. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet 2004; 364:1489.
- Kappos L, Polman CH, Freedman MS, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006; 67:1242.
- Clerico M, Faggiano F, Palace J, et al. Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis. Cochrane Database Syst Rev 2008; :CD005278.
- Kinkel RP, Kollman C, O'Connor P, et al. IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology 2006; 66:678.
- Kappos L, Freedman MS, Polman CH, et al. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 2007; 370:389.
- Kappos L, Freedman MS, Polman CH, et al. 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 2009; 8:987.
- Edan G, Kappos L, Montalbán X, et al. Long-term impact of interferon beta-1b in patients with CIS: 8-year follow-up of BENEFIT. J Neurol Neurosurg Psychiatry 2014; 85:1183.
- Pittock SJ. Uncertain BENEFIT of early interferon beta-1b treatment. Lancet Neurol 2009; 8:970.
- Comi G, De Stefano N, Freedman MS, et al. Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial. Lancet Neurol 2012; 11:33.
- Comi G, Martinelli V, Rodegher M, et al. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 2009; 374:1503.
- Achiron A, Kishner I, Sarova-Pinhas I, et al. Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Arch Neurol 2004; 61:1515.
- Giovannoni G. The REFLEX study: a missed opportunity? Lancet Neurol 2012; 11:22.
- Goodin DS, Frohman EM, Garmany GP Jr, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002; 58:169.
- INTRODUCTION AND DEFINITION
- CLINICAL PRESENTATION
- Clinically isolated syndromes
- Radiologically isolated syndrome
- PROGRESSION TO MULTIPLE SCLEROSIS
- With a radiologically isolated syndrome
- After isolated optic neuritis
- After acute transverse myelitis
- McDonald diagnostic criteria
- - Applying the MRI criteria
- Oligoclonal bands
- Antimyelin antibodies
- - Clinical trials
- Glatiramer acetate
- Intravenous immune globulin
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS