Early Identification of Clinically Isolated Syndrome
[PreCISe]) in patients with isolated neurological episodes and MRI suggestive of MS have demonstrated the usefulness of immunomodulatory therapy in delaying the occurrence of a second relapse.12–15
As a result of the evidence from these studies,
immunomodulatory therapy is now approved for use in MS from the very first relapse. All immunomodulatory drugs have demonstrated their usefulness compared with placebo in different stages of the disease, with the efficacy proving to be better the earlier therapy is started. An early diagnosis of MS is therefore important for counselling individual patients and making decisions on the use of evidence-based disease-modifying treatments.
The Development of Criteria for the Diagnosis of Multiple Sclerosis
The diagnosis of MS is currently based on clinical parameters such as medical history and neurological examination, and paraclinical measures such as MRI, cerebrospinal fluid (CSF) examination and evoked potential testing.
Poser Diagnostic Criteria
Traditionally, diagnostic criteria for MS stated that a diagnosis of CDMS required clinical evidence of two or more lesions on at least two occasions.16
In 1983, these criteria were expanded by Poser et al. to include the use of paraclinical parameters such as evoked potentials and CSF findings.17
Poser et al. defined diagnostic
categories and the highest degree of confidence was for CDMS, which was achieved when two relapses were identified, each confirmed by clinical examination, separated in space and time. However, these criteria anteceded MRI and thus did not give specific recommendations on how to use this (now) important paraclinical tool.
The Impact of the Introduction of Magnetic Resonance Imaging
MRI has been shown to be the single most informative diagnostic procedure in recent years. Areas of abnormality on T2-weighted or proton-density-weighted images in a pattern highly characteristic for MS occur in more than 95% of patients with clinically definite disease and in 50–70% of patients with a CIS. MRI is also a powerful method for excluding other diseases that might simulate MS, which is a critical additional diagnostic step.
Based on developments on MRI techniques, in 1988 Paty et al.18 proposed criteria for MS diagnosis that were supported by the presence of four or more lesions or three lesions, one of which needed to be periventricular. These criteria were prospectively evaluated in CIS patients and showed high sensitivity, but relatively low specificity, for the development of CDMS. Later, Fazekas et al.19 proposed a modification of the MRI criteria. This consisted of the consideration of three or more lesions with at least two of the following characteristics:
• periventricular; • infratentorial; and • larger than 6mm.
when retrospectively evaluated in established MS and other disorders. However, when applied prospectively in CIS patients their performance was inferior in predicting conversion to CDMS.21
EUROPEAN NEUROLOGICAL REVIEW
These criteria showed both high sensitivity and specificity for MS diagnosis20
The Barkhof–Tintoré Criteria In 1997 Barkhof et al.22
proposed a model of four parameters that
predicted conversion to CDMS better than previous or existing models. Those parameters were the presence of the following types of lesions:
• ≥1 gadolinium-enhancing; • ≥1 juxtacortical; • ≥1 infratentorial; and • ≥3 periventricular.
The Barkhof criteria were further modified by Tintoré et al.23 They
allowed the gadolinium-enhancing lesion to be replaced by nine T2 lesions and introduced the concept of having at least three of the four Barkhof parameters. This enabled Tintoré et al. to achieve a higher accuracy and better balance between sensitivity and specificity for predicting CIS conversion to CDMS.
The McDonald Criteria
In 2001, an international panel published new guidelines for the diagnosis of MS. As with the Poser criteria, these relied on objective evidence of dissemination in time and space. These criteria (commonly referred to as the McDonald criteria1
in recognition of the
panel’s chair, W Ian McDonald), included MRI evidence to support DIS and DIT. These criteria represented the first constructive effort to address how to use non-invasive observations in conjunction with clinical findings. The MRI DIS criteria chosen by the panel were those proposed by Barkhof et al.22
and Tintoré et al.,23 with the addition that a spinal cord lesion could substitute a brain lesion.
An alternative criterion introduced for DIS consisted of the presence of at least two MRI lesions plus positive CSF (i.e. the presence of oligoclonal bands or an elevated immunoglobulin G index). To support the evidence for DIT, these criteria require a gadolinium-enhancing lesion on a MRI scan obtained at least three months after CIS onset and in a separate location from the initial clinical event or a new T2 lesion on a scan subsequent to a reference one obtained at least three months after CIS onset. When retrospectively applied to CIS cohorts, the 2001 McDonald criteria showed high specificity for CDMS, but limited sensitivity.24,25
The Updated McDonald Criteria
The international panel re-convened in 2005 to review progress since the original criteria were published, evaluate whether the global framework of the criteria continued to be appropriate and determine whether any kind of revision should be recommended. In fact, changes in the 2001 criteria were proposed2
in order to simplify and
clarify issues that had caused some difficulty and misinterpretation, particularly concerning imaging and CSF findings. With respect to DIT demonstration, two new ways of detecting MS have replaced those previously used:
•
detection of a gadolinium-enhancing lesion at least three months after CIS onset if not at the site corresponding to the initial event; and
• detection of a new T2 lesion appearing at any time compared with a reference scan taken at least 30 days after the onset of the initial clinical event.
For DIS, the role of spinal cord lesions has been redefined: 91
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