Early Identification of Clinically Isolated Syndrome
The Queen Square group proposal also removed the option to include gadolinium enhancement as a feature of DIS and suggested only T2 lesions and their location be considered. The modified DIT criteria require ≥ one new T2 lesion(s) at three-month follow-up, regardless of when the reference MRI was performed.4,30
The accuracy of these new
criteria was confirmed in the results of a study carried out by the Magnetic Imaging in Multiple Sclerosis (MAGNIMS) group. This study showed similar specificity for CDMS using the Queen Square group criteria compared with the 2005 and 2001 McDonald criteria (87 versus 88 versus 91%, respectively). At the same time, sensitivity was improved (72 versus 60 versus 47%), see Table 1.3
Although the delay required for a second MRI scan may prevent incorrect and premature diagnosis, there is evidence that the presence of non-enhancing and enhancing lesions on a single MRI, even if obtained within the first three months after the first symptom, could be sufficient to establish DIT. This is because it is likely that this combination reflects lesions in different stages of evolution.5
Although highly specific (86%), these criteria have been shown to have a rather low sensitivity (45%). There is also some concern about misdiagnosis, as other entities such as acute disseminated encephalomyelitis can often present with a mixed pattern of enhancing and non-enhancing lesions at the same time point.31
This
new proposal only would therefore only apply to typical CIS occurring between 14 and 50 years of age.
With all the new evidence available, the European multicentre collaborative research network, Magnetic Imaging in MS (MAGNIMS) has proposed new algorithms for MS diagnosis (see Table 2 and Figure 1):32
• a MRI scan performed at any time demonstrating DIS and showing at least one asymptomatic gadolinium-enhancing and non-enhancing lesion is evidence for DIT;
•
a MRI scan performed at any time and showing DIS, but without any enhancing lesions or with all lesions enhancing, requires a second MRI to demonstrate new T2 or gadolinium-enhancing lesions; and
•
a MRI scan performed at any time not showing DIS or DIT requires further follow-up scans to confirm DIS and/or DIT.
The recommended DIS criteria are those proposed by Swanton in 2005.29
DIT criteria can be fulfilled by:
• the presence of one or more asymptomatic gadolinium-enhancing and non-enhancing lesions, irrespective of the time of the scan; or
1.
McDonald WI, Compston A, Edan G, et al., Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis, Ann Neurol, 2001;50:121–7.
2. 3.
Polman CH, Reingold SC, Edan G, et al., Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald Criteria’, Ann Neurol, 2005;58:840–46.
Swanton JK, Rovira A, Tintoré M, et al., MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study, Lancet Neurol, 2007;6:667–86.
4. 5.
Tur C, Tintoré M, Rovira A, et al., Very early scans for demonstrating dissemination in time in multiple sclerosis, Mult Scler, 2008;14:631–5.
Rovira A, Swanton JK, Tintoré M, et al., A single, early 9. 7. 8.
MRI scan for diagnosing multiple sclerosis, Arch Neurol, 2009;66:587–92.
6.
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: 944–9.
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;131:808–17.
Charil A, Yousry TA, Rovaris M, et al., MRI and the diagnosis of multiple sclerosis: expanding the concept of ‘no better explanation’, Lancet Neurol, 2006;5(10): 841–52.
Miller DH, Weinshenker BG, Filippi M, et al., Differential 10. 11.
Francisco C Pérez-Miralles is a Clinical Neurologist at the Multiple Sclerosis Centre of Catalonia (CEM-Cat), at the Vall d’Hebron University Hospital in Barcelona, where he is developing his PhD thesis on magnetic resonance imaging techniques and grey-matter atrophy development in multiple sclerosis (MS), and the Department of Medicine at the Universitat Autònoma de Barcelona. He received his medical training at the La Fe Hospital in Valencia, where he gained his first experiences in the MS unit.
Filipe Palavra is a Neurology Resident at the General Hospital of the ‘Centro Hospitalar de Coimbra – EPE’. His special field of interest is demyelinating disorders affecting the central nervous system, namely multiple sclerosis (MS). He is an intern at the Clinical Neuroimmunology Unit of the Vall d’Hebron University Hospital and a Member of the Portuguese Neurological Society and Portuguese MS Study Group.
Xavier Montalban is Director of the Multiple Sclerosis (MS) Centre of Catalonia, Director of Neuroscience at Vall d’Hebron University Hospital in Barcelona and Professor of Neurology at the Universitat Autònoma de Barcelona. He sits on Scientific, Editorial and Medical boards of the MS International Federation, European School for Neuroimmunology, European Charcot Foundation and MS and steering committees.
•
the presence of a new T2 and/or gadolinium-enhancing lesion compared to a previous scan, irrespective of the time of the reference scan.
Implications of the New Criteria
MRI is not only a diagnostic tool but also prognostic tool, as it can predict conversion to CDMS. Therefore, MRI can help in making decisions on the use of disease-modifying drugs. The role of CSF abnormalities, other paraclinical tests and the impact of three Tesla or higher field MRI findings must still be defined in the new guidelines.
Changes in criteria can affect the results of future clinical trials, as was observed in the transition between the Poser and McDonald criteria. An earlier diagnosis of MS based on an MRI may change the disease prognosis when compared with patients diagnosed with MS in the past, but does not really affect the overall prognosis (Will Rogers phenomenon).33
Such changes in criteria make it difficult
to compare the results of studies based on new and old criteria. Despite these concerns, it is hoped that simplifying MS criteria will help neurologists, as the new criteria are easier to implement in daily clinical evaluation and aid in the choice of treatment considered after a first attack. n
diagnosis of suspected multiple sclerosis: a consensus approach, Mult Scler, 2008;14:1157–74.
Ebers GC, Rice G, et al., 16-year long-term follow-up of interferon beta 1b in patients with multiple sclerosis, Mult Scler, 2005;11(Suppl. 1):S156.
Johson KP, Ford CC, Lisak RP, Wolinsky JS, Neurologic consequence of delaying glatiramer acetate therapy for multiple sclerosis: 8-year data, Acta Neurol Scand, 2005;111(1):42–7.
12.
Jacobs LD, Beck RW, Simon JH, et al., Intramuscular interferon-beta-1a therapy initiated during a first demyelinating event in multiple sclerosis, New Engl J Med, 2000;343: 898–904.
13.
Comi G, Filippi M, Barkhof F, et al., Early Treatment of Multiple Sclerosis Study Group. Effect of early interferon
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