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One method involves use of MRI to detect central vein sign (CVS) in MRI images. The CVS is a hypointense vessel at the center of a hyperintense focal lesion, and various retrospective analyses have revealed an association between a greater percentage of lesions being CVS and a diagnosis of MS.
“This is a very frequent finding in MS patients, but it’s a very infrequent finding in non-MS patients, specifically radiological mimics or clinical mimics that are typically confused with MS at the time of clinical diagnosis, and could lead to misdiagnosis. The idea here of a central vein sign is to use it diagnostically as early as possible in the evaluation of the MS, and use it as complementary to the existing McDonald criteria to improve sensitivity and specificity,” Pascal Sati, PhD, said in an interview. Dr. Sati presented an overview of the topic at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is associate professor of neurology at Cedars Sinai Medical Center in Los Angeles and the director of the neuroimaging program in the department of neurology at Cedars Sinai.
The findings could address an important issue in MS. “Misdiagnosis is a big problem in multiple sclerosis, and it has been for a long time. There are recent surveys of physicians that show that something like 95% of MS physicians have seen a case of misdiagnosis in the last year,” Kevin Patel, MD, said in an interview. Dr. Patel is assistant professor of neurology at the University of California, Los Angeles, and moderated the session where Dr. Sati presented.
What is the diagnostic threshold of CVS positivity?
A key question is what percentage of lesions should be CVS positive (CVS+) to predict a diagnosis of MS. One meta-analysis found that an average of 73% CVS positivity in MS patients, but levels below 40% in conditions that can mimic MS, such as migraine (22%), cerebral small vessel disease (28.5%), and neuromyelitis optica spectrum disorder (33.5%). However, both biological and technical effects can influence that percentage. The percentage is lower among older patients with MS, and those with vascular comorbidities, likely due to noninflammatory or ischemic plaques, or other lesion types, said Dr. Sati.
On the technical side, lower field strengths tend to reveal a lower proportion of CVS than higher field strengths, which are more sensitive. However, the choice of MRI technique can influence sensitivity, and the optimized T2* EPI and FLAIR* techniques have been shown to reveal higher percentages of CVS, even at lower field strengths like the commonly available 3-T.
Forty percent CVS positivity has been suggested as a diagnostic for MS, but this can be time consuming to determine in patients with large numbers of lesions. An alternative is to analyze a subset of lesions and make a diagnosis if these lesions display the CVS. For example, ‘Select 3*’ would establish an MS diagnosis if at least 3 brain lesions have the CVS, or the ‘6-lesion rule’ would establish an MS diagnosis if at least 6 out 10 brain lesions have the CVS. Recent retrospective studies have supported these simplified diagnostic criteria, suggesting that these approaches perform similarly to the 40% rule.
What will change clinical practice?
However, retrospective studies aren’t enough to change international diagnostic guidelines and clinical practice. Dr. Sati is part of a group of investigators from the North American Imaging in MS (NAIMS) Cooperative that is conducting a large prospective diagnostic study (CAVS-MS) with a $7.2 million grant from the National Institutes of Health, which is currently recruiting 400 patients being evaluated for MS. The MRI protocol will use the optimized T2* EPI/FLAIR* techniques developed by Dr. Sati on 3-T scanners. “It’s a twofold goal: First the evaluation of the diagnostic power of the central vein sign in a real-world cohort, and then the validation of the advanced MRI technology that we’re developing to image the central vein sign clinically,” said Dr. Sati.
Neurologists generally are becoming more aware of these techniques, according to Dr. Patel, but they aren’t yet widely used outside of research settings.
“We haven’t collected enough evidence to really warrant wide implementation. I suspect that that’s one of the major reasons why it is that we don’t see this deployed more widely. I think there’ll be a bit of time before this is integrated to the standard sequences that are done for evaluation of multiple sclerosis,” said Dr. Patel.
The technique must contend with comorbid factors, especially vascular comorbidities such as hypertension, diabetes, or high cholesterol, that can cause white matter hyperintensities as individuals age. “This can create difficulties with using this procedure, because if you have small vessel disease at the same time you have MS, you have much more T2 lesion volume. It becomes a little bit more difficult to suss out whether the person has MS. So there’s a little bit of work that needs to be done along those lines as well,” said Dr. Patel.
With more research, the technology has the potential to improve MS diagnosis, both among community neurologists and even among specialists, according to Dr. Patel. “There are definitely cases that are rather ambiguous that even though they present at a major academic center, it’s sometimes very difficult for us to determine as to whether the person has multiple sclerosis or not. And this sort of technique can potentially help us in distinguishing those cases. Sometimes even after they see folks at tertiary centers, folks still don’t have a definitive diagnosis,” said Dr. Patel.
Dr. Sati and Dr. Patel have no relevant financial disclosures.
One method involves use of MRI to detect central vein sign (CVS) in MRI images. The CVS is a hypointense vessel at the center of a hyperintense focal lesion, and various retrospective analyses have revealed an association between a greater percentage of lesions being CVS and a diagnosis of MS.
“This is a very frequent finding in MS patients, but it’s a very infrequent finding in non-MS patients, specifically radiological mimics or clinical mimics that are typically confused with MS at the time of clinical diagnosis, and could lead to misdiagnosis. The idea here of a central vein sign is to use it diagnostically as early as possible in the evaluation of the MS, and use it as complementary to the existing McDonald criteria to improve sensitivity and specificity,” Pascal Sati, PhD, said in an interview. Dr. Sati presented an overview of the topic at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is associate professor of neurology at Cedars Sinai Medical Center in Los Angeles and the director of the neuroimaging program in the department of neurology at Cedars Sinai.
The findings could address an important issue in MS. “Misdiagnosis is a big problem in multiple sclerosis, and it has been for a long time. There are recent surveys of physicians that show that something like 95% of MS physicians have seen a case of misdiagnosis in the last year,” Kevin Patel, MD, said in an interview. Dr. Patel is assistant professor of neurology at the University of California, Los Angeles, and moderated the session where Dr. Sati presented.
What is the diagnostic threshold of CVS positivity?
A key question is what percentage of lesions should be CVS positive (CVS+) to predict a diagnosis of MS. One meta-analysis found that an average of 73% CVS positivity in MS patients, but levels below 40% in conditions that can mimic MS, such as migraine (22%), cerebral small vessel disease (28.5%), and neuromyelitis optica spectrum disorder (33.5%). However, both biological and technical effects can influence that percentage. The percentage is lower among older patients with MS, and those with vascular comorbidities, likely due to noninflammatory or ischemic plaques, or other lesion types, said Dr. Sati.
On the technical side, lower field strengths tend to reveal a lower proportion of CVS than higher field strengths, which are more sensitive. However, the choice of MRI technique can influence sensitivity, and the optimized T2* EPI and FLAIR* techniques have been shown to reveal higher percentages of CVS, even at lower field strengths like the commonly available 3-T.
Forty percent CVS positivity has been suggested as a diagnostic for MS, but this can be time consuming to determine in patients with large numbers of lesions. An alternative is to analyze a subset of lesions and make a diagnosis if these lesions display the CVS. For example, ‘Select 3*’ would establish an MS diagnosis if at least 3 brain lesions have the CVS, or the ‘6-lesion rule’ would establish an MS diagnosis if at least 6 out 10 brain lesions have the CVS. Recent retrospective studies have supported these simplified diagnostic criteria, suggesting that these approaches perform similarly to the 40% rule.
What will change clinical practice?
However, retrospective studies aren’t enough to change international diagnostic guidelines and clinical practice. Dr. Sati is part of a group of investigators from the North American Imaging in MS (NAIMS) Cooperative that is conducting a large prospective diagnostic study (CAVS-MS) with a $7.2 million grant from the National Institutes of Health, which is currently recruiting 400 patients being evaluated for MS. The MRI protocol will use the optimized T2* EPI/FLAIR* techniques developed by Dr. Sati on 3-T scanners. “It’s a twofold goal: First the evaluation of the diagnostic power of the central vein sign in a real-world cohort, and then the validation of the advanced MRI technology that we’re developing to image the central vein sign clinically,” said Dr. Sati.
Neurologists generally are becoming more aware of these techniques, according to Dr. Patel, but they aren’t yet widely used outside of research settings.
“We haven’t collected enough evidence to really warrant wide implementation. I suspect that that’s one of the major reasons why it is that we don’t see this deployed more widely. I think there’ll be a bit of time before this is integrated to the standard sequences that are done for evaluation of multiple sclerosis,” said Dr. Patel.
The technique must contend with comorbid factors, especially vascular comorbidities such as hypertension, diabetes, or high cholesterol, that can cause white matter hyperintensities as individuals age. “This can create difficulties with using this procedure, because if you have small vessel disease at the same time you have MS, you have much more T2 lesion volume. It becomes a little bit more difficult to suss out whether the person has MS. So there’s a little bit of work that needs to be done along those lines as well,” said Dr. Patel.
With more research, the technology has the potential to improve MS diagnosis, both among community neurologists and even among specialists, according to Dr. Patel. “There are definitely cases that are rather ambiguous that even though they present at a major academic center, it’s sometimes very difficult for us to determine as to whether the person has multiple sclerosis or not. And this sort of technique can potentially help us in distinguishing those cases. Sometimes even after they see folks at tertiary centers, folks still don’t have a definitive diagnosis,” said Dr. Patel.
Dr. Sati and Dr. Patel have no relevant financial disclosures.
One method involves use of MRI to detect central vein sign (CVS) in MRI images. The CVS is a hypointense vessel at the center of a hyperintense focal lesion, and various retrospective analyses have revealed an association between a greater percentage of lesions being CVS and a diagnosis of MS.
“This is a very frequent finding in MS patients, but it’s a very infrequent finding in non-MS patients, specifically radiological mimics or clinical mimics that are typically confused with MS at the time of clinical diagnosis, and could lead to misdiagnosis. The idea here of a central vein sign is to use it diagnostically as early as possible in the evaluation of the MS, and use it as complementary to the existing McDonald criteria to improve sensitivity and specificity,” Pascal Sati, PhD, said in an interview. Dr. Sati presented an overview of the topic at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is associate professor of neurology at Cedars Sinai Medical Center in Los Angeles and the director of the neuroimaging program in the department of neurology at Cedars Sinai.
The findings could address an important issue in MS. “Misdiagnosis is a big problem in multiple sclerosis, and it has been for a long time. There are recent surveys of physicians that show that something like 95% of MS physicians have seen a case of misdiagnosis in the last year,” Kevin Patel, MD, said in an interview. Dr. Patel is assistant professor of neurology at the University of California, Los Angeles, and moderated the session where Dr. Sati presented.
What is the diagnostic threshold of CVS positivity?
A key question is what percentage of lesions should be CVS positive (CVS+) to predict a diagnosis of MS. One meta-analysis found that an average of 73% CVS positivity in MS patients, but levels below 40% in conditions that can mimic MS, such as migraine (22%), cerebral small vessel disease (28.5%), and neuromyelitis optica spectrum disorder (33.5%). However, both biological and technical effects can influence that percentage. The percentage is lower among older patients with MS, and those with vascular comorbidities, likely due to noninflammatory or ischemic plaques, or other lesion types, said Dr. Sati.
On the technical side, lower field strengths tend to reveal a lower proportion of CVS than higher field strengths, which are more sensitive. However, the choice of MRI technique can influence sensitivity, and the optimized T2* EPI and FLAIR* techniques have been shown to reveal higher percentages of CVS, even at lower field strengths like the commonly available 3-T.
Forty percent CVS positivity has been suggested as a diagnostic for MS, but this can be time consuming to determine in patients with large numbers of lesions. An alternative is to analyze a subset of lesions and make a diagnosis if these lesions display the CVS. For example, ‘Select 3*’ would establish an MS diagnosis if at least 3 brain lesions have the CVS, or the ‘6-lesion rule’ would establish an MS diagnosis if at least 6 out 10 brain lesions have the CVS. Recent retrospective studies have supported these simplified diagnostic criteria, suggesting that these approaches perform similarly to the 40% rule.
What will change clinical practice?
However, retrospective studies aren’t enough to change international diagnostic guidelines and clinical practice. Dr. Sati is part of a group of investigators from the North American Imaging in MS (NAIMS) Cooperative that is conducting a large prospective diagnostic study (CAVS-MS) with a $7.2 million grant from the National Institutes of Health, which is currently recruiting 400 patients being evaluated for MS. The MRI protocol will use the optimized T2* EPI/FLAIR* techniques developed by Dr. Sati on 3-T scanners. “It’s a twofold goal: First the evaluation of the diagnostic power of the central vein sign in a real-world cohort, and then the validation of the advanced MRI technology that we’re developing to image the central vein sign clinically,” said Dr. Sati.
Neurologists generally are becoming more aware of these techniques, according to Dr. Patel, but they aren’t yet widely used outside of research settings.
“We haven’t collected enough evidence to really warrant wide implementation. I suspect that that’s one of the major reasons why it is that we don’t see this deployed more widely. I think there’ll be a bit of time before this is integrated to the standard sequences that are done for evaluation of multiple sclerosis,” said Dr. Patel.
The technique must contend with comorbid factors, especially vascular comorbidities such as hypertension, diabetes, or high cholesterol, that can cause white matter hyperintensities as individuals age. “This can create difficulties with using this procedure, because if you have small vessel disease at the same time you have MS, you have much more T2 lesion volume. It becomes a little bit more difficult to suss out whether the person has MS. So there’s a little bit of work that needs to be done along those lines as well,” said Dr. Patel.
With more research, the technology has the potential to improve MS diagnosis, both among community neurologists and even among specialists, according to Dr. Patel. “There are definitely cases that are rather ambiguous that even though they present at a major academic center, it’s sometimes very difficult for us to determine as to whether the person has multiple sclerosis or not. And this sort of technique can potentially help us in distinguishing those cases. Sometimes even after they see folks at tertiary centers, folks still don’t have a definitive diagnosis,” said Dr. Patel.
Dr. Sati and Dr. Patel have no relevant financial disclosures.
FROM ACTRIMS FORUM 2022