Internal Medicine Journal Club

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In patients with suspected multiple sclerosis, how well do clinical criteria predict the eventual development of definite MS?

Background:

Indentifying multiple lesions and clinical deficits is key to the diagnosis of MS. In 1983, before MRI, Poser developed clinical criteria for MS. The criteria rely on identifying new symptoms over time (DIT - 'dissemination in time'). After introductionof MRI, Barkhof developed MRI criteria. In 2003, an International Panel developed the McDonald criteria to include the MRI criteria in revised criteria (McDonald criteria (from UpToDate, you will be ask to sign in before viewing the table of criteria). This would allow quicker diagnoses because the MRI would allow indentification of dessimination in space (DIS), e.g. finding multiple MRI lesions at clinical presentions. Below, two articles follow patients with the McDonald criteria until they are diagnosed with the Poser criteria.

Bottom line:

There have been two independent validations of the McDonald criteria:

First article (Tintoré):

Gold standard:

"A diagnosis of conversion to CDMS [using Poser's clinical criteria] was made when new symptoms occurred after an interval of at least 1 month and only when other diagnoses had been excluded. CDMS was diagnosed when there was a second attack with a new neurologic abnormality that was confirmed by examination."

Patients:

139 patients. 86 were followed for three years. 53 (38%) were lost to follow-up.

Results:

CDMS was diagnosed in 38 patients (27%) (median conversion time 400 days).

Upon initial evaluation, e.g. baseline, '77 patients (56%) fulfilled McDonald criteria for dissemination in space. Of these, 33 (43%) developed CDMS (p < 0,001) during follow-up.'

For prediction of status at 3 years:

Sensitivity: 87%

Specificity: 56%

Second article (Dalton):

Gold standard:

"All patients were assessed clinically at baseline, 3 months, 1 year, and 3 years, and those with further relapses with new signs disseminated in space and time (at least 1 month after the clinically isolated syndrome) were classified as having clinically definite MS according to the criteria of Poser and colleagues."

Patients:

95 patients. 50 were followed for three years. 45 (47%) were lost to follow-up.

Results:

CDMS was diagnosed in 19 patients (20%)

Upon initial evaluation, e.g. baseline, 'Using the McDonald criteria, we found that dissemination in space was present in 43 of 119 (36%) patients when brain MRI findings alone were considered; this increased to 47 of 119 (40%) patients when spinal cord findings were included'

For prediction of status at 3 years:

Sensitivity 79
Specificity 77

Warning: I cannot replicate their calculations. I get specificity of 59%.

References:

1. Tintoré M, et al. New diagnostic criteria for multiple sclerosis: application in first demyelinating episode.
Neurology. 2003;60:27-30.
PMID: 12525713

2. Dalton, CM, Brex, PA, Miszkiel, KA, et al. Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol 2002; 52:47.
PMID: 12112046

1. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis.
Ann Neurol. 2001;50:121-7.
PMID: 11456302

1. Assessment of MRI criteria for a diagnosis of MS. Offenbacher H; Fazekas F; Schmidt R; Freidl W; Flooh E; Payer F; Lechner H. Neurology 1993;43:905-9.
PMID: 8274173

2. Barkhof F, Filippi M, Miller DH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997; 120: 2059–2069.
PMID: 9397021

1.Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research proposals. Ann Neurol . 1983; 13: 227–231.
PMID: 6847134