Slowly expanding lesions are in most MS patients, and are not the same as rim lesions

Design

systematic review and meta-analysis with random-effects generalised linear mixed models, PROSPERO registered

Population

20 studies, 4,786 patients with multiple sclerosis; mean age 43.6 years, 63.7% female

Primary outcome

pooled proportion of slowly expanding lesions among T2 lesions and proportion of patients with at least one

Effect

14% of T2 lesions (95% CI 10–21); 78% of patients (67–85) with ≥1; 11% (6–20) overlapped with paramagnetic rim lesions

Chronic active lesions are the imaging expression of smouldering inflammation behind the scenes in multiple sclerosis, and two different markers are used for them: slowly expanding lesions, defined on serial conventional MRI by concentric expansion, and paramagnetic rim lesions, defined by a rim on susceptibility-weighted imaging. They are often spoken about as though they were the same thing. This meta-analysis of 20 studies in 4,786 patients tested that.

Slowly expanding lesions accounted for 14% of all T2 lesions (95% CI 10–21), but 78% of patients (67–85) had at least one. Mean per-patient volume was 1.42 mL against 10.6 mL of total T2 lesion. The proportion of lesions that were slowly expanding was similar in relapsing-remitting and progressive disease at about 15%, though more patients with progressive disease had at least one.

The overlap figure is the finding: only 11% of slowly expanding lesions (6–20) also carried a paramagnetic rim. These are largely different lesion populations. Using one as a proxy for the other — in a trial endpoint, a prognostic statement or a treatment decision — is not supported. Heterogeneity was high throughout and no source for it was identified, which given the variety of definitions and imaging intervals in use is unsurprising and is itself part of the message.

• Slowly expanding lesions require serial MRI with consistent sequences and intervals — they cannot be called from a single scan.
• Paramagnetic rim lesions need susceptibility-sensitive sequences, which are not routine on many Indian scanners.
• Do not report or interpret the two markers interchangeably; they identified largely different lesions here.
• Neither marker currently has a treatment decision attached to it — this is prognostic and research imaging.
• When reading a trial that uses either as an endpoint, check which definition and which imaging interval were used.

Why it matters

Trials and clinics are increasingly quoting these markers, often as if a rim lesion and an expanding lesion were interchangeable evidence of the same process.

Don't overread it

This establishes how often these lesions are seen, not what they mean for an individual patient's prognosis or treatment.

The statistics, in plain English

The confidence intervals here are wide because these are pooled proportions across studies using different definitions — 14% of lesions with an interval from 10 to 21, and 11% overlap with an interval from 6 to 20, which is almost a fourfold range. High unexplained heterogeneity in a proportion meta-analysis usually means the studies were not measuring quite the same thing, and the authors name exactly that: different identification methods and different numbers and spacings of MRI time points.

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