Chronic active ‘rim’ lesions possible biomarkers in MS

Multiple sclerosis

By Mardi Chapman

15 Aug 2019

Chronic rim lesions on 7-T or 3-T susceptibility-based brain MRI are associated with more aggressive disease in MS and may have utility as potential biomarkers for disease progression and future treatment efficacy.

A US study of almost 200 patients with MS found 34% of patients had between one to three lesions and 22% had four or more lesions.

The prevalence of clinically progressive MS was 1.6-fold higher in individuals with four or more chronic rim lesions than in those without a rim lesion (43% v 27%; p=0.03).

Patients with four or more lesions also reached motor and cognitive disability at a younger age as measured by scores such as the Expanded Disability Status Scale (EDSS), MS Severity Scale (MSSS), Paced Auditory Symbol Addition Test (PASAT, 3-second version), and Symbol Digit Modality Test (SDMT).

In a subgroup of younger patients under 50 years of age, the prevalence of clinically progressive MS was 3.2–fold higher in individuals with four or more chronic rim lesions rims than in those without (28% v 9%; p < 0.05).

Mean normalised volumes of the brain, white matter, thalamus, putamen, and caudate nucleus were lower in patients with four or more rim lesions.

“The most relevant and novel findings of this research can be summarized as follows: first, independently of clinical phenotype and disease-modifying therapy, most patients with MS (56%) had at least 1 chronic active lesion, supporting the notion that microglia/macrophage–mediated inflammation is a prominent feature of MS that is not the primary target of current treatments.”

“Second, individuals with multiple chronic active lesions had more aggressive disease (higher lesion load and ventricular volumes and lower white matter and basal ganglia volumes) and reached higher motor and cognitive disability or transitioned to disease progression at younger age, despite treatment.”

Professor Richard Macdonell, director of neurology at Austin Health, told the limbic the lesions may prove to be a potential biomarker in clinical trials for a type of MS which is not responsive to current treatments.

“It’s an observation that we are able to see evidence of chronic smoldering lesions on MR if you look closely – and you have to look very closely as I think they are harder to see than the standard T2 lesions – but they potentially represent ongoing inflammation and may portend a worse prognosis.”

He said the findings would not yet impact individual patients and there were no trials looking whether reducing the number of lesions could make an impact on the clinical outcome.

However it was no surprise that patients with fairly advanced disease had the smoldering plaques.

“It probably speaks to the fact that these patients who have more chronic smoldering inflammation in the brain, probably due to microglia and macrophages, develop more pathology and therefore more symptoms over time.”

He said that most MS drugs were targeted against B and T lymphocytes, not microglia and macrophages.

“So there is potentially another treatment option if we could find a drug that could get through the blood-brain barrier and suppress this type of inflammation.”

He added that while the software was available for this type of in vivo imaging, it required radiologists with the time and interest to develop the expertise in counting the lesions.

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