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WEST PALM BEACH, FLORIDA — , according to one of numerous PRL studies at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“We think this supports other evidence that PRLs are going to be a useful biomarker for MS,” reported Susan Gauthier, DO, an associate professor of neurology and radiology at Weill Cornell University in New York City.
In a simple study, patients with PRLs at baseline were compared with patients without PRLs over a 4-year period, showing that baseline PRLs correlated with worse cognitive function over time.
Of the study cohort, with a median age of 42 years, 5 patients had clinically isolated syndrome (CIS), 81 had relapsing-remitting MS, and 5 had secondary progressive MS. On baseline MRI, 41% of patients had PRLs.
Cognitive function was tracked over time with the Brief International Cognitive Assessment for MS (BICAMS). The components include the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test (BVMT).
Univariate linear model relationships were used to look for a relationship between baseline PRLs and cognitive function. Multiple linear models were performed “with all possible iterations” to further explore the most significant variables. At baseline, no differences were seen in any cognitive test between those with or without PRLs.
Cognitive Function Changes at 4 Years
Those with at least one PRL had significantly lower SDMT (P = 0.046) and BVLT (P = 0.0292) at 4 years. There was no significant difference for CVLT scores.
The findings are consistent with the potential for PRLs to serve “as an imaging marker to identify MS patients at risk for cognitive decline,” said Hannah Schwartz, BA, a mentee of Dr. Gauthier and senior clinical research coordinator in the Department of Neurology at Weill Cornell. Ms. Schwartz presented the data at ACTRIMS Forum Cutting Edge symposium.
Over the past 10 years, there has been a growing body of evidence that the presence of PRLs, which are generally described as a spot of demyelination in the central nervous system surrounded by a rim of iron-laden immune cells such as microglia and macrophages, are prognostically important. The sizable number of studies at the ACTRIMS meeting on PRLs, which so far appear to be unique to MS, suggests the field is maturing.
Routine Measurement of PRLs Is Feasible
One set of data from the CAVS-MS study suggest that routine measurement of this biomarker can be integrated into routine imaging. CAVS-MS is a 2-year international multicenter evaluation of MS biomarkers with 11 participating sites that has collected PRL data on 420 patients.
Overall, PRLs were identified in 39% of these patients. However, patients were divided by typical versus atypical presentation, defined by such factors as an uncharacteristic pattern of attacks, accelerated progression, or radiologically isolated lesions. Among the 201 patients with a typical presentation, at least 1 PRL was found in 53%. Among the 219 with atypical presentations, PRLs were seen in only 26%.
The greater rate of PRLs and the greater number of PRLs per positive patient in the typical presentation group (median 3 vs 2) were highly significant (both P < .0001), reported Brian Renner, MD, a research associate in the neuroimaging program, Department of Neurology, Cedars-Sinai Hospital, Los Angeles.
In this analysis, the PRLs were identified by a single experienced rater with T2- and T1-weighted imaging using 2024 North American Imaging in Multiple Sclerosis (NAIMS) criteria for PRL. These criteria were published earlier this year in Brain.
One message from this study is that “PRL measurement in a large multicenter cohort is feasible,” according to Dr. Renner. This is not only important based on the potential role of PRLs as a prognostic biomarker but also for diagnosis, given the fact that PRLs when present appear to confirm a diagnosis of MS.
Misdiagnosis of MS continues to be a problem, and Dr. Renner said that these appear “to be capable of differentiating MS lesions from non-MS disease mimics.” However, he stated that further validation studies are needed.
Can PRLs Be Prevented or Reversed?
The data on PRLs have generated interest in whether they can be prevented or reversed once they appear. This might be dependent on first determining who is at risk. Another study presented at ACTRIMS suggested that it might not be complex. Lesion size might be critical.
In this study, 233 images were evaluated in 64 patients participating in an observational study at the UMass Memorial Medical Center, Worcester, Massachusetts.
In a univariable analysis, a long list of patient factors, disease characteristics, and imaging characteristics correlated with an increased risk of develop PRLs. These included patient age, disease duration, lesion volume, enhancement pattern (ring vs nodular), and use of disease modifying therapies.
When a regression analysis of these factors was performed, “none of the predictive factors on the univariable analyses were significant after including lesion size in the model,” reported Mustafa Al Gburi, MD, a fellow in neuroimaging at UMass.
While his data did show that exposure to steroids did not appear to reduce risk of developing PRLs, he is now running follow-up to see if specific disease-modifying therapies are more or less preventive for the development of PRL. Because of the limited number of patients and follow-up, it is now too early to tell.
Overall, the risk of PRLs appears to grow substantially at a lesion size of greater than 11 mm, Dr. Al Gburi reported. He believes that this might be “a simple bedside marker to determine patients at future risk of chronic active lesions.”
PRLs might not just be a diagnostic and prognostic tool. Dr. Gauthier said that PRLs are at least a theoretical treatment target. While their immediate promise is in monitoring disease, she thinks the evidence would predict a benefit if PRLs could be prevented or reversed.
Dr. Gauthier reports financial relationships with Genentech, Sanofi-Genzyme, and Mallinckrodt. Dr. Renner and Dr. Al Gburi report no potential conflicts of interest.
WEST PALM BEACH, FLORIDA — , according to one of numerous PRL studies at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“We think this supports other evidence that PRLs are going to be a useful biomarker for MS,” reported Susan Gauthier, DO, an associate professor of neurology and radiology at Weill Cornell University in New York City.
In a simple study, patients with PRLs at baseline were compared with patients without PRLs over a 4-year period, showing that baseline PRLs correlated with worse cognitive function over time.
Of the study cohort, with a median age of 42 years, 5 patients had clinically isolated syndrome (CIS), 81 had relapsing-remitting MS, and 5 had secondary progressive MS. On baseline MRI, 41% of patients had PRLs.
Cognitive function was tracked over time with the Brief International Cognitive Assessment for MS (BICAMS). The components include the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test (BVMT).
Univariate linear model relationships were used to look for a relationship between baseline PRLs and cognitive function. Multiple linear models were performed “with all possible iterations” to further explore the most significant variables. At baseline, no differences were seen in any cognitive test between those with or without PRLs.
Cognitive Function Changes at 4 Years
Those with at least one PRL had significantly lower SDMT (P = 0.046) and BVLT (P = 0.0292) at 4 years. There was no significant difference for CVLT scores.
The findings are consistent with the potential for PRLs to serve “as an imaging marker to identify MS patients at risk for cognitive decline,” said Hannah Schwartz, BA, a mentee of Dr. Gauthier and senior clinical research coordinator in the Department of Neurology at Weill Cornell. Ms. Schwartz presented the data at ACTRIMS Forum Cutting Edge symposium.
Over the past 10 years, there has been a growing body of evidence that the presence of PRLs, which are generally described as a spot of demyelination in the central nervous system surrounded by a rim of iron-laden immune cells such as microglia and macrophages, are prognostically important. The sizable number of studies at the ACTRIMS meeting on PRLs, which so far appear to be unique to MS, suggests the field is maturing.
Routine Measurement of PRLs Is Feasible
One set of data from the CAVS-MS study suggest that routine measurement of this biomarker can be integrated into routine imaging. CAVS-MS is a 2-year international multicenter evaluation of MS biomarkers with 11 participating sites that has collected PRL data on 420 patients.
Overall, PRLs were identified in 39% of these patients. However, patients were divided by typical versus atypical presentation, defined by such factors as an uncharacteristic pattern of attacks, accelerated progression, or radiologically isolated lesions. Among the 201 patients with a typical presentation, at least 1 PRL was found in 53%. Among the 219 with atypical presentations, PRLs were seen in only 26%.
The greater rate of PRLs and the greater number of PRLs per positive patient in the typical presentation group (median 3 vs 2) were highly significant (both P < .0001), reported Brian Renner, MD, a research associate in the neuroimaging program, Department of Neurology, Cedars-Sinai Hospital, Los Angeles.
In this analysis, the PRLs were identified by a single experienced rater with T2- and T1-weighted imaging using 2024 North American Imaging in Multiple Sclerosis (NAIMS) criteria for PRL. These criteria were published earlier this year in Brain.
One message from this study is that “PRL measurement in a large multicenter cohort is feasible,” according to Dr. Renner. This is not only important based on the potential role of PRLs as a prognostic biomarker but also for diagnosis, given the fact that PRLs when present appear to confirm a diagnosis of MS.
Misdiagnosis of MS continues to be a problem, and Dr. Renner said that these appear “to be capable of differentiating MS lesions from non-MS disease mimics.” However, he stated that further validation studies are needed.
Can PRLs Be Prevented or Reversed?
The data on PRLs have generated interest in whether they can be prevented or reversed once they appear. This might be dependent on first determining who is at risk. Another study presented at ACTRIMS suggested that it might not be complex. Lesion size might be critical.
In this study, 233 images were evaluated in 64 patients participating in an observational study at the UMass Memorial Medical Center, Worcester, Massachusetts.
In a univariable analysis, a long list of patient factors, disease characteristics, and imaging characteristics correlated with an increased risk of develop PRLs. These included patient age, disease duration, lesion volume, enhancement pattern (ring vs nodular), and use of disease modifying therapies.
When a regression analysis of these factors was performed, “none of the predictive factors on the univariable analyses were significant after including lesion size in the model,” reported Mustafa Al Gburi, MD, a fellow in neuroimaging at UMass.
While his data did show that exposure to steroids did not appear to reduce risk of developing PRLs, he is now running follow-up to see if specific disease-modifying therapies are more or less preventive for the development of PRL. Because of the limited number of patients and follow-up, it is now too early to tell.
Overall, the risk of PRLs appears to grow substantially at a lesion size of greater than 11 mm, Dr. Al Gburi reported. He believes that this might be “a simple bedside marker to determine patients at future risk of chronic active lesions.”
PRLs might not just be a diagnostic and prognostic tool. Dr. Gauthier said that PRLs are at least a theoretical treatment target. While their immediate promise is in monitoring disease, she thinks the evidence would predict a benefit if PRLs could be prevented or reversed.
Dr. Gauthier reports financial relationships with Genentech, Sanofi-Genzyme, and Mallinckrodt. Dr. Renner and Dr. Al Gburi report no potential conflicts of interest.
WEST PALM BEACH, FLORIDA — , according to one of numerous PRL studies at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“We think this supports other evidence that PRLs are going to be a useful biomarker for MS,” reported Susan Gauthier, DO, an associate professor of neurology and radiology at Weill Cornell University in New York City.
In a simple study, patients with PRLs at baseline were compared with patients without PRLs over a 4-year period, showing that baseline PRLs correlated with worse cognitive function over time.
Of the study cohort, with a median age of 42 years, 5 patients had clinically isolated syndrome (CIS), 81 had relapsing-remitting MS, and 5 had secondary progressive MS. On baseline MRI, 41% of patients had PRLs.
Cognitive function was tracked over time with the Brief International Cognitive Assessment for MS (BICAMS). The components include the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test (BVMT).
Univariate linear model relationships were used to look for a relationship between baseline PRLs and cognitive function. Multiple linear models were performed “with all possible iterations” to further explore the most significant variables. At baseline, no differences were seen in any cognitive test between those with or without PRLs.
Cognitive Function Changes at 4 Years
Those with at least one PRL had significantly lower SDMT (P = 0.046) and BVLT (P = 0.0292) at 4 years. There was no significant difference for CVLT scores.
The findings are consistent with the potential for PRLs to serve “as an imaging marker to identify MS patients at risk for cognitive decline,” said Hannah Schwartz, BA, a mentee of Dr. Gauthier and senior clinical research coordinator in the Department of Neurology at Weill Cornell. Ms. Schwartz presented the data at ACTRIMS Forum Cutting Edge symposium.
Over the past 10 years, there has been a growing body of evidence that the presence of PRLs, which are generally described as a spot of demyelination in the central nervous system surrounded by a rim of iron-laden immune cells such as microglia and macrophages, are prognostically important. The sizable number of studies at the ACTRIMS meeting on PRLs, which so far appear to be unique to MS, suggests the field is maturing.
Routine Measurement of PRLs Is Feasible
One set of data from the CAVS-MS study suggest that routine measurement of this biomarker can be integrated into routine imaging. CAVS-MS is a 2-year international multicenter evaluation of MS biomarkers with 11 participating sites that has collected PRL data on 420 patients.
Overall, PRLs were identified in 39% of these patients. However, patients were divided by typical versus atypical presentation, defined by such factors as an uncharacteristic pattern of attacks, accelerated progression, or radiologically isolated lesions. Among the 201 patients with a typical presentation, at least 1 PRL was found in 53%. Among the 219 with atypical presentations, PRLs were seen in only 26%.
The greater rate of PRLs and the greater number of PRLs per positive patient in the typical presentation group (median 3 vs 2) were highly significant (both P < .0001), reported Brian Renner, MD, a research associate in the neuroimaging program, Department of Neurology, Cedars-Sinai Hospital, Los Angeles.
In this analysis, the PRLs were identified by a single experienced rater with T2- and T1-weighted imaging using 2024 North American Imaging in Multiple Sclerosis (NAIMS) criteria for PRL. These criteria were published earlier this year in Brain.
One message from this study is that “PRL measurement in a large multicenter cohort is feasible,” according to Dr. Renner. This is not only important based on the potential role of PRLs as a prognostic biomarker but also for diagnosis, given the fact that PRLs when present appear to confirm a diagnosis of MS.
Misdiagnosis of MS continues to be a problem, and Dr. Renner said that these appear “to be capable of differentiating MS lesions from non-MS disease mimics.” However, he stated that further validation studies are needed.
Can PRLs Be Prevented or Reversed?
The data on PRLs have generated interest in whether they can be prevented or reversed once they appear. This might be dependent on first determining who is at risk. Another study presented at ACTRIMS suggested that it might not be complex. Lesion size might be critical.
In this study, 233 images were evaluated in 64 patients participating in an observational study at the UMass Memorial Medical Center, Worcester, Massachusetts.
In a univariable analysis, a long list of patient factors, disease characteristics, and imaging characteristics correlated with an increased risk of develop PRLs. These included patient age, disease duration, lesion volume, enhancement pattern (ring vs nodular), and use of disease modifying therapies.
When a regression analysis of these factors was performed, “none of the predictive factors on the univariable analyses were significant after including lesion size in the model,” reported Mustafa Al Gburi, MD, a fellow in neuroimaging at UMass.
While his data did show that exposure to steroids did not appear to reduce risk of developing PRLs, he is now running follow-up to see if specific disease-modifying therapies are more or less preventive for the development of PRL. Because of the limited number of patients and follow-up, it is now too early to tell.
Overall, the risk of PRLs appears to grow substantially at a lesion size of greater than 11 mm, Dr. Al Gburi reported. He believes that this might be “a simple bedside marker to determine patients at future risk of chronic active lesions.”
PRLs might not just be a diagnostic and prognostic tool. Dr. Gauthier said that PRLs are at least a theoretical treatment target. While their immediate promise is in monitoring disease, she thinks the evidence would predict a benefit if PRLs could be prevented or reversed.
Dr. Gauthier reports financial relationships with Genentech, Sanofi-Genzyme, and Mallinckrodt. Dr. Renner and Dr. Al Gburi report no potential conflicts of interest.
FROM ACRIMS FORUM 2024