Multiple Sclerosis
Table 2: Summary of McDonald, Modified McDonald, and MAGNIMS Magnetic Resonance Imaging Criteria for Dissemination in Space and Time for Multiple Sclerosis
McDonald 200127 ≥3 of:
McDonald 200528 ≥3 of:
Dissemination in Space (on Baseline MRI) ≥9 T2 lesions or ≥1 Gd-enhancing lesion ≥3 periventricular lesions
MAGNIMS29
Lesion(s) in each of ≥2 Characteristic Locations:
≥9 T2 lesions or ≥1 Gd-enhancing lesion ≥3 periventricular lesions
1 cord lesion can replace 1 brain lesion
≥1 posterior fossa lesion or spinal cord lesion Any number of cord
≥1 periventricular ≥1 juxtacortical
≥1 juxtacortical lesion ≥1 juxtacortical lesion ≥1 posterior fossa ≥1 posterior fossa lesion
≥1 spinal cord All lesions in symptomatic
lesions can be included regions excluded in in total lesion count
brainstem and spinal cord syndromes
Dissemination in Time (on Follow-up MRI) 1. ≥Gd-enhancing lesion 1. ≥Gd-enhancing lesion 1. Simultaneous presence at least 3 months after at least 3 months after of asymptomatic CIS onset (if not related CIS onset (if not related Gd-enhancing and to CIS)
to CIS)
2. A new T2 lesion with reference to a prior
scan obtained at least 3
2. A new T2 lesion with reference to a prior
scan obtained at least 3
non-enhancing lesions at any time
2. A new T2 and/or
Gd-enhancing lesion on follow-up MRI irrespective
months after CIS onset months after CIS onset of timing of baseline scan
CIS = clinically isolated syndrome; Gd = gadolinium; MAGNIMS = magnetic imaging in multiple sclerosis; MRI = magnetic resonance imaging. Source: Swanton et al., 200730
and Montalban et al., 2010.31
or more T2 lesion(s) in two or more of four characteristic locations (juxtacortical, periventricular, infratentorial, and spinal cord).
Dissemination in time requires only a new T2 lesion on any follow-up scan or the simultaneous presence of a non-enhancing asymptomatic T2 lesion and a gadolinium (Gd)-enhancing lesion on the same scan. The MAGNIMS criteria are summarized in Table 2.
Decision-making Process in the Treatment of Multiple Sclerosis
Results from a number of studies support early initiation of each of the injectable treatments for MS at the time of initial presentation with a CIS and at least two typical abnormalities on brain MRI. These studies include the:
• Controlled high-risk subjects Avonex MS prevention study (CHAMPS);32 • •
Early treatment Of MS (ETOMS);33
Betaferon/Betaseron in newly emerging MS For initial treatment (BENEFIT);34
and •
Early glatiramer acetate treatment in delaying conversion to clinically-definite MN in subjects Presenting with a CIS (PreCISe).35
62
While adverse events with injectable treatments can deter patients, injection site reactions can be minimized with local measures and
US NEUROLOGY
Recently a workshop of the European multicenter collaborative research network that studies MRI in MS (MAGNIMS) reviewed these new criteria. The group revised the MRI-derived information that should be retained and the diagnostic criteria have now been updated further. This allows for even greater ease in diagnosis while minimizing false positives.31
While most of these placebo-controlled trials ran for only two years, prospectively-planned follow-up data from the BENEFIT study also showed that early treatment with IFNβ-1β positively affected the rate of conversion of initial CIS to clinically definite MS for up to five years of follow-up.34
This fact is generally accepted by both prescribers and insurers in the US, with minimal obstacles to commencing therapy early in the disease course. Three of the four available injectable agents have been approved by the US Food and Drug Administration (FDA) for treatment at the time of CIS with abnormal brain MRI. Insurance companies are generally required to fund currently available MS treatments on this basis. The situation differs in other parts of the world, however, where cost and conservatism among physicians may restrict or delay access to proven effective treatments.
and neurologists in the US now readily prescribe a DMT at this time. In fact, there are instances when neurologists may be too hasty in initiating treatment, administering it to patients without a typical CIS presentation and/or with non-specific MRI findings that do not necessarily show classic signs of demyelination.36
As mentioned
above, treatment initiation should require a definitive diagnosis of a clinical demyelinating event with at least one documented abnormality on neurologic exam. Patients without clear signs of MS who receive DMTs may question the necessity of treatment and, in fact, DMT efficacy in asymptomatic patients has never been proven. A schematic of current treatment decisions in MS is given in Figure 1.
The decision to start treatment at the first clinical signs of disease (CIS) must be taken by the individual neurologist in conjunction with the patient. Sometimes it is difficult to convince a patient that receiving frequent, regular injections of a preventative DMT with the potential for frequent side-effects is in their best interest, especially after initial symptoms have subsided, thus creating a barrier to optimal treatment. For such patients, physicians may opt to use steroids for symptom management and await a change on a subsequent MRI scan (dissemination in time) in order to provide further evidence that the disease is indeed likely to follow a relapsing course.
The initial DMT chosen often reflects personal preference and experience, as each neurologist will have their favored treatments. There are no head-to-head trials of DMTs for treatment at the time of CIS. The selection of high- or low-dose IFNβ versus glatiramer acetate may depend on many factors, including symptom severity, MRI activity, injection frequency, history of severe depression and other individual factors. Treatment response tends to be idiosyncratic and unpredictable. Breakthrough disease in patients taking their first-line DMT is relatively common, although all of the available DMTs are useful as first-line therapy in at least some patients. Head-to-head studies in RRMS have shown equivalence among current injectable DMTs, as well as a rapid onset of action.35,37–39
Currently, no evidence exists to
suggest that glatiramer acetate may be inferior in efficacy to the IFNβs, as was previously believed by some practitioners.
Currently, the decision to initiate treatment is often taken after documentation of a CIS with MRI evidence of prior and/or ongoing disease activity29,31
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