Early Identification of Clinically Isolated Syndrome – How this is Best Achieved and the Implications for Patient Outcomes
Francisco C Pérez-Miralles,1 Filipe Palavra2 and Xavier Montalban3
1. Clinical Neurologist; 2. Neurology Resident Intern; 3. Director of Neuroscience and Director, Multiple Sclerosis Centre of Catalonia (CEM-Cat), Vall d’Hebron University Hospital, Barcelona, and Universitat Autònoma de Barcelona
Magnetic resonance imaging (MRI) evidence for dissemination in space (DIS) and dissemination in time (DIT) are used within the McDonald criteria for the diagnosis of multiple sclerosis (MS). These criteria are complex and in some patients several MRI examinations are needed to achieve an accurate diagnosis. In order to make an earlier diagnosis of clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS), new criteria have been proposed in which DIS and DIT requirements are simpler, maximising sensitivity and conserving specificity. These data have led to a new proposal of MRI criteria for MS diagnosis. The historical evolution of MS criteria and the new evidence are reviewed in this article.
Clinically isolated syndrome, clinically definite multiple sclerosis, magnetic resonance imaging, diagnostic criteria, dissemination in time, dissemination in space
Disclosure: Francisco C Pérez-Miralles and Filipe Palavra have no conflicts of interest to declare. Xavier Montalban has received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, sanofi-aventis, Teva Pharmaceuticals and Almirall. Received: 4 October 2010 Accepted: 19 November 2010 Citation: European Neurological Review, 2010;5(2):90–4 Correspondence: Francisco C Pérez-Miralles, Unitat de Neuroimunologia Clínica (UNIC), EUI, planta 2, Hospital Universitari Vall d’Hebron, Passeig de la Vall d’Hebron, 119–129, 08035 Barcelona, Spain. E: email@example.com
Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) that mainly affects young adults and is characterised by an inflammatory demyelination of different areas of the CNS occurring at different time points. MS has several forms of presentation, including episodic subacute periods of worsening (the most common, initially), gradual progressive deterioration of neurological function or a combination of both. These different presentations have been given standardised names – relapsing–remitting (RR), secondary progressive, primary progressive and progressive-relapsing – describing the clinical phenotype of the disease.
Unfortunately reliable biomarkers that enable the prediction of the clinical course of MS from the beginning of the disease are yet to be identified. Approximately 85% of patients start out with RRMS and the presentation, despite the possibility of having multifocal signs and symptoms, is frequently monosymptomatic. Patients often present with unilateral optic neuritis, a brainstem syndrome or partial myelitis, which are the more common initial symptoms in MS. These presentations are known as clinically isolated syndromes (CIS).
In recent years, changes in MS diagnostic criteria have been proposed, mainly due to the incorporation of updated magnetic resonance imaging (MRI) criteria1,2
incorporating these criteria have now been published.3–5 long-term follow-up study, Beck et al.6
and Fisniku et al.7
and new data from trials In a
clinically-definite MS (CDMS) developed in 56–82% of patients with abnormal MRI and in approximately 20% with normal MRI at
presentation. As no single clinical feature or diagnostic test is sufficient for MS diagnosis, criteria have been developed and modified combining different clinical, biological and radiological information. These criteria essentially focus on the demonstration of the more relevant aspects of disease course – the dissemination of lesions in space (DIS) and the dissemination of lesions in time (DIT) – and the exclusion of alternative causes that can mimic MS.8,9
Why is Early Diagnosis Important? The efficacy of interferon-beta in RRMS patients has been clearly demonstrated. Results from a follow-up study on patients who participated in the pivotal beta-1b interferon trial showed the benefit of early treatment. The disability, mortality and MRI scores of patients from the treated group were better than the placebo-group patients treated in the extension phase of the study.10
were obtained from the pivotal glatiramer acetate trial. Here, a significantly lower proportion of patients from the placebo group treated with glatiramer acetate during the extension phase were neurologically stabilised or improved compared with patients who had been treated with glatiramer acetate from the start of the trial.11
Phase III clinical trials (the Controlled High-Risk Subjects Avonex® Multiple Sclerosis Prevention Study [CHAMPS], the Early Treatment Of Multiple Sclerosis [ETOMS] study, the Betaferon®/Betaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment [BENEFIT] trial and the Study to Evaluate Early Glatiramer Acetate Treatment in Delaying Conversion to CDMS of Subjects Presenting With CIS
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