Imaging: Meeting Review^©

Abstracts written for <http://www.multiplesclerosis.com> in 2002 and reprinted here with permission.

MRIs document increased benefit of giving higher-dose interferons more frequently

Magnetic resonance imaging (MRI) assessments were an important part of the EVIDENCE trials, the first head-to-head comparison of two versions of IFN beta-1a: Rebif® (44 mcg subcutaneously, given three times weekly) vs Avonex® (30 mcg intramuscularly, once a week).* According to David KB Li, treatment effects appeared early on MRI and were significantly more pronounced with Rebif than with Avonex.† Furthermore, the increased benefit following use of a more frequently given, higher- dose IFN beta-1a was sustained month to month and extended to all measures of activity. For example, the relative reduction in combined unique (CU) lesion counts from months 1 through 6 in the Rebif group was 22%, 41%, 67%, 56%, 63% and 57%. CU count reduction in the Avonex group were consistently lower. MRI evidence of improved therapeutic efficacy for Rebif was associated with significantly improved clinical outcome.

* European-North American Comparative efficacy (EVIDENCE) study
† 325 patients in each group had MRI scans performed (with and without gadolinium infusion) at 4-week intervals from before the first dose to 24 weeks on the study
[S67.004/A503,A504]

Early MS missed with current MRI criteria

Both enhancing lesions and the Barkhof criteria are relatively strong predictors for development of clinically definite MS (CDMS) in patients who have had a positive MRI at their initial neurological event. They may, however, only identify patients with an accelerated disease pace. An analysis of placebo patients from the CHAMPS* trial suggests that even when enhancing lesions or Barkhof criteria are not met, the vast majority of patients go on to develop combined CDMS/MRI outcomes after only a short follow up (18 months). This, according to Jack H. Simon, indicates that there is ongoing demyelinating activity. Thus, he says: "Current diagnostic criteria for MS do not address this large population of patients in the earliest stages of their disease…"

* Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS)
[S67.001/A502, A503]

New McDonald criteria deemed valid and highly specific

Traditionally, MS has been diagnosed on clinical evidence of dissemination in time and space. McDonald and colleagues recently offered new diagnostic criteria integrating MRI findings into the diagnostic scheme. Catherine M Dalton and colleagues recently completed a study validating the McDonald criteria in patients with clinically isolated syndromes (CIS) suggestive of MS. Seventy-nine patients were recruited and imaged within three months of symptom onset and for up to 3 years. Using baseline and three month scans the McDonald MRI criteria alone had a sensitivity of 59%, specificity of 92%, positive predictive value of 83% and negative predictive value of 76% for the development of clinically definite MS. Specificity was higher than either an abnormal baseline MRI brain scan (30%) or the traditional Barkhof criteria (78%). According to Dalton: "In making a diagnosis of a lifelong condition specificity is more important that sensitivity, therefore the McDonald criteria are valid."

[S26.001/A172, A173]

Specificity of new McDonald criteria challenged by other researchers

Lilvia Di Legge and colleagues also tested the reliability of the revised McDonald criteria of MS in patients with clinically isolated syndromes (CIS). A series of consecutive CIS patients showing at least 3 typical white matter lesions were followed with monthly Gd-enhanced brain MRIs (n=53). At 3-month scan, sensitivity of the new McDonald's criteria was 89% (17/19) while specificity was 68% (23/24). Positive predictive value and negative predictive value were 61% and 92% respectively. In contrast to the findings of Dalton's group, preliminary results of this investigation showed the new McDonald criteria had low specificity. Di Legge did say, however, that it is likely that the specificity will increase with longer follow-up. Promising though is the high negative predictive value of the new criteria which may be able to detect those patients who will remain disease free.

[S26.002/A173]

Cortical gray matter atrophy occurs early and contributes to disability

Cortical gray matter (GM) abnormalities resulting from axonal transection and apoptotic neuronal loss subsequent to cortical demyelination are significant in patients with multiple sclerosis. Nicola De Stefano and fellow researchers evaluated cortical GM in patients with definite relapsing-remitting (n=65) or primary progressive (n=25) multiple sclerosis. The group used conventional proton T1-weighted MR images to measure atrophy. Age differences in the two MS groups were corrected relative to an age-matched normal control (NC) group. All MS patients had significantly lower cortical GM values than the control individuals. Notably, even early-stage MS patients (<5 years) and those with only mild disability (EDSS 2) had significantly lower cortical GM values than the control subjects. De Stefano says that these study results confirm the early onset of significant GM abnormalities in MS patients. There was also a significant negative correlation between clinical disability and cortical GM values. Thus, GM pathology probably contributes significantly to neurological impairment, especially in PPMS patients.

[S67.003/A503]

Preliminary consensus guidelines for MRI scanning now available for discussion and comment: CMSC website: MSCARE.ORG

An expert consensus meeting was convened in 2001 to help standardize MRI protocols worldwide. The project, sponsored by the Consortium of MS Centers (CMSC), will provide guidelines both for diagnostic neuroimaging and follow-up MRIs. The meeting resulted in 10 preliminary guidelines which are now available for review, discussion and comment on the CMSC website (MSCARE.ORG).

[PO3.086/A210,A211]