Evidence Mounts for Paramagnetic Rim Lesions in Diagnosing MS

Nancy A. Melville

February 28, 2022

WEST PALM BEACH, FL – The presence of paramagnetic rim lesions (PRLs) on MRI may help in the diagnosis of multiple sclerosis (MS), as well as in predicting more severe disease course, new research suggests.

Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers note.

Dr Amjad AlTokhis

"Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions," the lead author of both studies, Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, told Medscape Medical News.

Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.

"This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis," said AlTokhis.

"These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS," she added.

The findings were presented here at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.

Sign of Aggressive Disease?

Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.

In the first study, AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.

At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs primary progressive MS and clinically isolated syndrome).

At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.

Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.

The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher compared with those without the lesions (ARMSS, 6.7 vs 5.0).

After the median 9-year follow-up, disease severity remained higher among those with vs those without the lesions (ARMSS, 7.3 vs 6.3).

Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).

"Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability —thus, possibly useful in earlier treatment and a potential target for therapies," AlTokhis said.

"Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker," she added.

AlTokhis noted that "detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign."

Diagnostic Value

The second study, presented at the meeting by co-investigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, California, reported on the significance of the rim lesions in MS diagnosis.

It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).

Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.

Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.

Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.

"We've shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation ― which was likely related to the nature of the cohort," Renner said.

Promising Data

During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School in Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.

Dr Christopher Hemond

"We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity," said Hemond, who was not involved with the research.

"There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation," he added.

Hemond noted that, unlike in Renner's study, the bulk of previous studies have indicated that rim lesions "are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS."

Commenting for Medscape Medical News, Hemond noted the results from Renner's ongoing study "are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS," while AlTokis' study "adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”

Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.

"Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time," he said.

During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tennessee, noted the growing importance of the role of rim lesions in clinical research.

"It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials," she said.

Renner's study received funding from the Race to Erase MS Foundation. AlTokhis, Renner, and Hemond have reported no relevant financial relationships.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021: Abstract AP2.4. Presented February 24, 2022.

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