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Physical activity is a growing priority for patients with MS
SAN DIEGO – As , researchers have developed a mobile app to encourage young patients with the disease to become more active. The smartphone-based app provides tailored physical activity information, coaching advice, and tools to increase social connectedness.
A pilot study examining whether the intervention changes activity, depression, and fatigue levels should be wrapped up later this year, but it looks as though the app is succeeding.
“The feedback we’ve gotten so far from our coaches is that the kids seem highly motivated,” said one of the creators, E. Ann Yeh, MD, professor in the faculty of medicine at the University of Toronto and director of the pediatric MS and neuroinflammatory disorders program at the Hospital for Sick Children.
Preliminary work showed that use of the app was associated with a 31% increase in physical activity.
They discussed this and other studies of the role of exercise in MS at the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Higher levels of depression and fatigue
Studies show that youths with MS who are less physically active are more likely to experience higher levels of fatigue and depression. Evidence suggests just 15-30 more minutes of moderate to vigorous physical activity (MVPA) makes a clinical difference in terms of improved depression and fatigue scores, said Dr. Yeh.
With moderate physical activity (for example, a brisk walk or raking the yard), the maximal heart rate (HRmax) reaches 64%-76%, while with vigorous physical activity (which includes jogging/running or participating in a strenuous fitness class), the HRmax reaches 77%-93%.
Dr. Yeh described vigorous physical activity as “the stuff that makes you sweat, makes your heart rate go up, and makes you not be able to talk when you’re moving.”
As it stands, kids get very little MVPA – 9.5 min/day, which is well below the recommended 60 min/day. Adults do a bit better – 18.7 min/day of MVPA – but this is still below the recommended 30 min/day.
Being physically active improves fatigue for adults as well as kids, said Dr. Yeh. She referred to a network meta-analysis of 27 studies involving 1,470 participants that evaluated 10 types of exercise interventions, including yoga, resistance training, dance, and aquatic activities. It found that exercise “does move the needle,” she said. “Regardless of the kind of activity that was studied, fatigue seemed to improve.”
The authors of that study ranked aquatic exercise as the most effective intervention. “It’s possible that aquatics worked better because people who can’t move well feel more comfortable in the water,” Dr. Yeh said.
But she cautioned that the one study in the meta-analysis that found a “quite strong” effect of aquatic exercise was “very small.”
With regard to depression, which affects about 30% of people with MS, Dr. Yeh told meeting attendees, “unfortunately, the data are less clear” when it comes to physical activity for adults. One meta-analysis of 15 randomized controlled trials involving 331 exercising participants and 260 control persons found that only a few studies showed positive effects of exercise on depressive symptoms.
However, Dr. Yeh noted that in this review, the baseline depressive symptoms of participants were “above the cutoff level,” which makes it more difficult to demonstrate change in depression levels.
Clear structural effects
Researchers have also described clear brain structural and functional effects from being physically active. For example, MVPA has been shown to affect brain volume, and it has been associated with better optical coherence tomography (OCT) metrics, which measures retinal thinning.
As for the impact of exercise on memory deficits, which is of interest, given the current focus on Alzheimer’s disease, “the jury is still out,” said Dr. Yeh. One 24-week randomized controlled trial found no difference in results on the Brief Repeatable Battery of Neuropsychological tests between participants who engaged in progressive aerobic exercise and control persons.
However, said Dr. Yeh, “the problem may not be with the intervention but with the outcome measures” and potentially with the populations studied.
It might be a different story for high-intensity exercise, though. A study by Danish researchers assessed the effects of a 24-week high-intensity intervention among 84 adult patients with mild-severe impairment.
The primary outcome of that study, which was the percentage of brain volume change, was not met, possibly because the study was too short. There were significant results for some secondary endpoints, including improved cardiorespiratory fitness and lower relapse rate.
“Even though on the face of it, it sounds like a negative study, there were important outcomes,” said Dr. Yeh.
Research into the possible mechanisms behind positive effects of physical activity is limited with regard to patients with MS, said Dr. Yeh. Some studies have implicated certain circulating factors, such as the cytokine irisin and brain-derived neurotrophic factor, but more work is needed, she said.
“There is need for further mechanistic knowledge related to exercise in MS, and this must be accomplished through prospective, randomized studies.”
While exercise likely makes some difference for MS patients, the problem is in getting them to be more active. “You can’t just write a prescription,” said Dr. Yeh.
“Patients should be doing whatever they can, but gradually, and should not go crazy at the beginning because they’ll just burn out,” she said.
She stressed that patients need to find what works for them personally. It’s also important for them to find ways to be active with a friend who can be “a motivator” to help sustain physical activity goals, said Dr. Yeh.
Patients can also look online for remote physical activity programs geared to people with MS, which popped up during the pandemic.
Improved mood, cognition, pain, sleep
In a comment, Marwa Kaisey, MD, assistant professor of neurology at Cedars-Sinai Medical Center, in Los Angeles, who cochaired the session highlighting the presentation, praised Dr. Yeh’s “excellent talk,” which highlighted the “strong benefit” of exercise for patients with MS.
“As a clinician, I often talk to my patients about the importance of physical exercise and have heard countless anecdotes of how their workout programs helped improve mood, cognition, pain, or sleep.”
However, she agreed there are several areas “where we need more data-driven solutions and a mechanistic understanding of the benefits of physical exercise.”
The pilot study was funded by the Consortium of Multiple Sclerosis Centers. The MS Society of Canada funded early work on the app, and the National MS Society is funding the trial of the app. Dr. Yeh receives support from the MS Society of Canada. Dr. Kaisey reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO – As , researchers have developed a mobile app to encourage young patients with the disease to become more active. The smartphone-based app provides tailored physical activity information, coaching advice, and tools to increase social connectedness.
A pilot study examining whether the intervention changes activity, depression, and fatigue levels should be wrapped up later this year, but it looks as though the app is succeeding.
“The feedback we’ve gotten so far from our coaches is that the kids seem highly motivated,” said one of the creators, E. Ann Yeh, MD, professor in the faculty of medicine at the University of Toronto and director of the pediatric MS and neuroinflammatory disorders program at the Hospital for Sick Children.
Preliminary work showed that use of the app was associated with a 31% increase in physical activity.
They discussed this and other studies of the role of exercise in MS at the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Higher levels of depression and fatigue
Studies show that youths with MS who are less physically active are more likely to experience higher levels of fatigue and depression. Evidence suggests just 15-30 more minutes of moderate to vigorous physical activity (MVPA) makes a clinical difference in terms of improved depression and fatigue scores, said Dr. Yeh.
With moderate physical activity (for example, a brisk walk or raking the yard), the maximal heart rate (HRmax) reaches 64%-76%, while with vigorous physical activity (which includes jogging/running or participating in a strenuous fitness class), the HRmax reaches 77%-93%.
Dr. Yeh described vigorous physical activity as “the stuff that makes you sweat, makes your heart rate go up, and makes you not be able to talk when you’re moving.”
As it stands, kids get very little MVPA – 9.5 min/day, which is well below the recommended 60 min/day. Adults do a bit better – 18.7 min/day of MVPA – but this is still below the recommended 30 min/day.
Being physically active improves fatigue for adults as well as kids, said Dr. Yeh. She referred to a network meta-analysis of 27 studies involving 1,470 participants that evaluated 10 types of exercise interventions, including yoga, resistance training, dance, and aquatic activities. It found that exercise “does move the needle,” she said. “Regardless of the kind of activity that was studied, fatigue seemed to improve.”
The authors of that study ranked aquatic exercise as the most effective intervention. “It’s possible that aquatics worked better because people who can’t move well feel more comfortable in the water,” Dr. Yeh said.
But she cautioned that the one study in the meta-analysis that found a “quite strong” effect of aquatic exercise was “very small.”
With regard to depression, which affects about 30% of people with MS, Dr. Yeh told meeting attendees, “unfortunately, the data are less clear” when it comes to physical activity for adults. One meta-analysis of 15 randomized controlled trials involving 331 exercising participants and 260 control persons found that only a few studies showed positive effects of exercise on depressive symptoms.
However, Dr. Yeh noted that in this review, the baseline depressive symptoms of participants were “above the cutoff level,” which makes it more difficult to demonstrate change in depression levels.
Clear structural effects
Researchers have also described clear brain structural and functional effects from being physically active. For example, MVPA has been shown to affect brain volume, and it has been associated with better optical coherence tomography (OCT) metrics, which measures retinal thinning.
As for the impact of exercise on memory deficits, which is of interest, given the current focus on Alzheimer’s disease, “the jury is still out,” said Dr. Yeh. One 24-week randomized controlled trial found no difference in results on the Brief Repeatable Battery of Neuropsychological tests between participants who engaged in progressive aerobic exercise and control persons.
However, said Dr. Yeh, “the problem may not be with the intervention but with the outcome measures” and potentially with the populations studied.
It might be a different story for high-intensity exercise, though. A study by Danish researchers assessed the effects of a 24-week high-intensity intervention among 84 adult patients with mild-severe impairment.
The primary outcome of that study, which was the percentage of brain volume change, was not met, possibly because the study was too short. There were significant results for some secondary endpoints, including improved cardiorespiratory fitness and lower relapse rate.
“Even though on the face of it, it sounds like a negative study, there were important outcomes,” said Dr. Yeh.
Research into the possible mechanisms behind positive effects of physical activity is limited with regard to patients with MS, said Dr. Yeh. Some studies have implicated certain circulating factors, such as the cytokine irisin and brain-derived neurotrophic factor, but more work is needed, she said.
“There is need for further mechanistic knowledge related to exercise in MS, and this must be accomplished through prospective, randomized studies.”
While exercise likely makes some difference for MS patients, the problem is in getting them to be more active. “You can’t just write a prescription,” said Dr. Yeh.
“Patients should be doing whatever they can, but gradually, and should not go crazy at the beginning because they’ll just burn out,” she said.
She stressed that patients need to find what works for them personally. It’s also important for them to find ways to be active with a friend who can be “a motivator” to help sustain physical activity goals, said Dr. Yeh.
Patients can also look online for remote physical activity programs geared to people with MS, which popped up during the pandemic.
Improved mood, cognition, pain, sleep
In a comment, Marwa Kaisey, MD, assistant professor of neurology at Cedars-Sinai Medical Center, in Los Angeles, who cochaired the session highlighting the presentation, praised Dr. Yeh’s “excellent talk,” which highlighted the “strong benefit” of exercise for patients with MS.
“As a clinician, I often talk to my patients about the importance of physical exercise and have heard countless anecdotes of how their workout programs helped improve mood, cognition, pain, or sleep.”
However, she agreed there are several areas “where we need more data-driven solutions and a mechanistic understanding of the benefits of physical exercise.”
The pilot study was funded by the Consortium of Multiple Sclerosis Centers. The MS Society of Canada funded early work on the app, and the National MS Society is funding the trial of the app. Dr. Yeh receives support from the MS Society of Canada. Dr. Kaisey reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO – As , researchers have developed a mobile app to encourage young patients with the disease to become more active. The smartphone-based app provides tailored physical activity information, coaching advice, and tools to increase social connectedness.
A pilot study examining whether the intervention changes activity, depression, and fatigue levels should be wrapped up later this year, but it looks as though the app is succeeding.
“The feedback we’ve gotten so far from our coaches is that the kids seem highly motivated,” said one of the creators, E. Ann Yeh, MD, professor in the faculty of medicine at the University of Toronto and director of the pediatric MS and neuroinflammatory disorders program at the Hospital for Sick Children.
Preliminary work showed that use of the app was associated with a 31% increase in physical activity.
They discussed this and other studies of the role of exercise in MS at the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Higher levels of depression and fatigue
Studies show that youths with MS who are less physically active are more likely to experience higher levels of fatigue and depression. Evidence suggests just 15-30 more minutes of moderate to vigorous physical activity (MVPA) makes a clinical difference in terms of improved depression and fatigue scores, said Dr. Yeh.
With moderate physical activity (for example, a brisk walk or raking the yard), the maximal heart rate (HRmax) reaches 64%-76%, while with vigorous physical activity (which includes jogging/running or participating in a strenuous fitness class), the HRmax reaches 77%-93%.
Dr. Yeh described vigorous physical activity as “the stuff that makes you sweat, makes your heart rate go up, and makes you not be able to talk when you’re moving.”
As it stands, kids get very little MVPA – 9.5 min/day, which is well below the recommended 60 min/day. Adults do a bit better – 18.7 min/day of MVPA – but this is still below the recommended 30 min/day.
Being physically active improves fatigue for adults as well as kids, said Dr. Yeh. She referred to a network meta-analysis of 27 studies involving 1,470 participants that evaluated 10 types of exercise interventions, including yoga, resistance training, dance, and aquatic activities. It found that exercise “does move the needle,” she said. “Regardless of the kind of activity that was studied, fatigue seemed to improve.”
The authors of that study ranked aquatic exercise as the most effective intervention. “It’s possible that aquatics worked better because people who can’t move well feel more comfortable in the water,” Dr. Yeh said.
But she cautioned that the one study in the meta-analysis that found a “quite strong” effect of aquatic exercise was “very small.”
With regard to depression, which affects about 30% of people with MS, Dr. Yeh told meeting attendees, “unfortunately, the data are less clear” when it comes to physical activity for adults. One meta-analysis of 15 randomized controlled trials involving 331 exercising participants and 260 control persons found that only a few studies showed positive effects of exercise on depressive symptoms.
However, Dr. Yeh noted that in this review, the baseline depressive symptoms of participants were “above the cutoff level,” which makes it more difficult to demonstrate change in depression levels.
Clear structural effects
Researchers have also described clear brain structural and functional effects from being physically active. For example, MVPA has been shown to affect brain volume, and it has been associated with better optical coherence tomography (OCT) metrics, which measures retinal thinning.
As for the impact of exercise on memory deficits, which is of interest, given the current focus on Alzheimer’s disease, “the jury is still out,” said Dr. Yeh. One 24-week randomized controlled trial found no difference in results on the Brief Repeatable Battery of Neuropsychological tests between participants who engaged in progressive aerobic exercise and control persons.
However, said Dr. Yeh, “the problem may not be with the intervention but with the outcome measures” and potentially with the populations studied.
It might be a different story for high-intensity exercise, though. A study by Danish researchers assessed the effects of a 24-week high-intensity intervention among 84 adult patients with mild-severe impairment.
The primary outcome of that study, which was the percentage of brain volume change, was not met, possibly because the study was too short. There were significant results for some secondary endpoints, including improved cardiorespiratory fitness and lower relapse rate.
“Even though on the face of it, it sounds like a negative study, there were important outcomes,” said Dr. Yeh.
Research into the possible mechanisms behind positive effects of physical activity is limited with regard to patients with MS, said Dr. Yeh. Some studies have implicated certain circulating factors, such as the cytokine irisin and brain-derived neurotrophic factor, but more work is needed, she said.
“There is need for further mechanistic knowledge related to exercise in MS, and this must be accomplished through prospective, randomized studies.”
While exercise likely makes some difference for MS patients, the problem is in getting them to be more active. “You can’t just write a prescription,” said Dr. Yeh.
“Patients should be doing whatever they can, but gradually, and should not go crazy at the beginning because they’ll just burn out,” she said.
She stressed that patients need to find what works for them personally. It’s also important for them to find ways to be active with a friend who can be “a motivator” to help sustain physical activity goals, said Dr. Yeh.
Patients can also look online for remote physical activity programs geared to people with MS, which popped up during the pandemic.
Improved mood, cognition, pain, sleep
In a comment, Marwa Kaisey, MD, assistant professor of neurology at Cedars-Sinai Medical Center, in Los Angeles, who cochaired the session highlighting the presentation, praised Dr. Yeh’s “excellent talk,” which highlighted the “strong benefit” of exercise for patients with MS.
“As a clinician, I often talk to my patients about the importance of physical exercise and have heard countless anecdotes of how their workout programs helped improve mood, cognition, pain, or sleep.”
However, she agreed there are several areas “where we need more data-driven solutions and a mechanistic understanding of the benefits of physical exercise.”
The pilot study was funded by the Consortium of Multiple Sclerosis Centers. The MS Society of Canada funded early work on the app, and the National MS Society is funding the trial of the app. Dr. Yeh receives support from the MS Society of Canada. Dr. Kaisey reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACTRIMS FORUM 2023
New digital tools hold promise for patients with MS
SAN DIEGO – A new wearable device detects, with a high degree of precision, various types of visual dysfunction, which eventually affects most patients with multiple sclerosis (MS). The device uses advanced digital technology to stimulate the retina and the occipital cortex while also stimulating the eye tracking system, and reports out this data, one of its developers, Jennifer Graves, MD, PhD, director of neuroimmunology research, University of California, San Diego, said in an interview.
“In one paradigm of testing, we can get both sets of information,” which eliminates the complicated equipment set-up used by neuro-ophthalmologists, and makes eye assessments more readily available, she said.
“We can make this accessible for more clinicians and more patients, even eventually having it in an emergency setting or an outpatient clinic setting.”
Dr. Graves discussed this and other next-generation digital tools at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Currently, patients with MS can use accelerometers that determine overall activity level and devices that detect heart rate variability. They can also access mobile apps that track symptoms and medication adherence.
Limited sensitivity of current tools
However, current tools used to determine disability in MS are limited. The classification of MS subtypes is largely retrospective, and the preferred Expanded Disability Status Scale (EDSS) is problematic, said Dr. Graves.
For example, she said, the EDSS lacks sensitivity to short-term changes, depends on ambulation, and only poorly captures upper-extremity disability. “We know our patients are experiencing change and we know the tools we have now aren’t capturing that.”
She used the example of a pianist who can no longer play well with her right hand, but this can’t be detected with current tools. A device that uses technology from the gaming and computer control industry “can quantify that” change, said Dr. Graves.
She added that . “Rather than having descriptive terms, these digital tools will help us quantitate change so we can take action.”
The new sensing devices use multiple sensors, including accelerometers, gyroscopes, and surface electrical signals in muscles to capture very precise temporal and textural information related to movement. Their development uses traditional signal processing as well as artificial intelligence approaches.
Dr. Graves’s device, the MSight, captures afferent and efferent visual function with a single mobile brain-computer interface.
At least 80% of patients with MS have some measurable dysfunction in the afferent system that oversees how light from the environment is turned into images in the brain, explained Dr. Graves. The efferent visual system that controls eye movements is also “profoundly impacted by MS” with, again, up to 80% of patients with MS experiencing related dysfunction, she said.
Her new visual system correlates with burden of MS disease, said Dr. Graves. “Having efferent and eye tracking problems correlates with overall disability and walking function.”
The information collected by this new device “tends to be really helpful even in people who don’t appear to be disabled with MS because it’s literally a window into the brain to let us see what’s happening,” said Dr. Graves.
She and her colleagues are testing the MSight device in clinical trials and have a provisional patent for it.
Finger and foot taps
Another device her team is developing detects minute changes over several months in finger and toe tap movements that are very difficult for the human eye to capture.
Dr. Graves reported on a cross sectional validation study of 17 patients with MS showing the foot and finger tap measures strongly correlated with the EDSS and patient-reported outcomes (P < .0001). A longitudinal analysis of 68 patients with MS found information on finger and foot taps distinguished those with progressive from those with relapsing MS.
“We found that in patients with progressive MS, the information in the signal we were capturing was changing, whereas someone with relapsing MS had a little bit of that but much less,” said Dr. Graves.
These and other novel, self-contained devices “will provide a set of neurological vital signs that we can put in the hands of clinicians and patients” with MS, as is currently being done in other specialties – for example, cardiology, said Dr. Graves.
Intriguing, exciting
In a comment, David Gosselin, PhD, associate professor, department of molecular medicine, Laval University, Quebec City, who cochaired the session featuring next-generation digital tools, said more sensitive monitoring technologies coming down the pipeline are “intriguing and exciting.”
While the devices are still in early development, “the eventual integration of such noninvasive technology that measures subtle limb muscle function has the potential to redefine clinical practice,” said Dr. Gosselin.
“The idea of sampling a patient’s ability to move about on a frequent basis, perhaps even daily, and to generate data profiles over time, certainly hold promise with respect to tracking disease evolution and responses to treatments on a scale not accessible before.”
A more immediate and comprehensive overview of a patient’s response to a treatment “could yield more rapid insights into the effectiveness of novel therapies tested in clinical trials,” said Dr. Gosselin. “This could have profound implications.”
Future digital devices may facilitate monitoring of patients in more remote communities, too, said Dr. Gosselin.
However, before these technologies can be introduced on a broad level, several outstanding issues will have to be addressed, the most important being the streams of data they generate, said Dr. Gosselin.
“This clearly has the potential to overwhelm neurologists in the assessment of their patients’ conditions,” he said. “Which information, and in which analyzed forms, truly provides meaningful insights into patients’ conditions will need to be identified, and this will take time.”
Privacy may be an issue, too, said Dr. Gosselin. Some patients may be less inclined to comply with a procedure “that can capture and record their life so extensively.”
And how health care insurance providers can interface with these comprehensive profiles of patients’ lives will also have to be considered, he said.
Dr. Graves has a provisional patent on the MSight device; has received research support from MMSS, Octave, Biogen EMD Serono, Novartis, ATARA Biotherapeutics, and ABM; has served on advisory boards for Bayer, Genentech, and TG therapeutic and a pediatric clinical trial steering committee for Novartis; and has consulted for Google. Dr. Gosselin reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO – A new wearable device detects, with a high degree of precision, various types of visual dysfunction, which eventually affects most patients with multiple sclerosis (MS). The device uses advanced digital technology to stimulate the retina and the occipital cortex while also stimulating the eye tracking system, and reports out this data, one of its developers, Jennifer Graves, MD, PhD, director of neuroimmunology research, University of California, San Diego, said in an interview.
“In one paradigm of testing, we can get both sets of information,” which eliminates the complicated equipment set-up used by neuro-ophthalmologists, and makes eye assessments more readily available, she said.
“We can make this accessible for more clinicians and more patients, even eventually having it in an emergency setting or an outpatient clinic setting.”
Dr. Graves discussed this and other next-generation digital tools at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Currently, patients with MS can use accelerometers that determine overall activity level and devices that detect heart rate variability. They can also access mobile apps that track symptoms and medication adherence.
Limited sensitivity of current tools
However, current tools used to determine disability in MS are limited. The classification of MS subtypes is largely retrospective, and the preferred Expanded Disability Status Scale (EDSS) is problematic, said Dr. Graves.
For example, she said, the EDSS lacks sensitivity to short-term changes, depends on ambulation, and only poorly captures upper-extremity disability. “We know our patients are experiencing change and we know the tools we have now aren’t capturing that.”
She used the example of a pianist who can no longer play well with her right hand, but this can’t be detected with current tools. A device that uses technology from the gaming and computer control industry “can quantify that” change, said Dr. Graves.
She added that . “Rather than having descriptive terms, these digital tools will help us quantitate change so we can take action.”
The new sensing devices use multiple sensors, including accelerometers, gyroscopes, and surface electrical signals in muscles to capture very precise temporal and textural information related to movement. Their development uses traditional signal processing as well as artificial intelligence approaches.
Dr. Graves’s device, the MSight, captures afferent and efferent visual function with a single mobile brain-computer interface.
At least 80% of patients with MS have some measurable dysfunction in the afferent system that oversees how light from the environment is turned into images in the brain, explained Dr. Graves. The efferent visual system that controls eye movements is also “profoundly impacted by MS” with, again, up to 80% of patients with MS experiencing related dysfunction, she said.
Her new visual system correlates with burden of MS disease, said Dr. Graves. “Having efferent and eye tracking problems correlates with overall disability and walking function.”
The information collected by this new device “tends to be really helpful even in people who don’t appear to be disabled with MS because it’s literally a window into the brain to let us see what’s happening,” said Dr. Graves.
She and her colleagues are testing the MSight device in clinical trials and have a provisional patent for it.
Finger and foot taps
Another device her team is developing detects minute changes over several months in finger and toe tap movements that are very difficult for the human eye to capture.
Dr. Graves reported on a cross sectional validation study of 17 patients with MS showing the foot and finger tap measures strongly correlated with the EDSS and patient-reported outcomes (P < .0001). A longitudinal analysis of 68 patients with MS found information on finger and foot taps distinguished those with progressive from those with relapsing MS.
“We found that in patients with progressive MS, the information in the signal we were capturing was changing, whereas someone with relapsing MS had a little bit of that but much less,” said Dr. Graves.
These and other novel, self-contained devices “will provide a set of neurological vital signs that we can put in the hands of clinicians and patients” with MS, as is currently being done in other specialties – for example, cardiology, said Dr. Graves.
Intriguing, exciting
In a comment, David Gosselin, PhD, associate professor, department of molecular medicine, Laval University, Quebec City, who cochaired the session featuring next-generation digital tools, said more sensitive monitoring technologies coming down the pipeline are “intriguing and exciting.”
While the devices are still in early development, “the eventual integration of such noninvasive technology that measures subtle limb muscle function has the potential to redefine clinical practice,” said Dr. Gosselin.
“The idea of sampling a patient’s ability to move about on a frequent basis, perhaps even daily, and to generate data profiles over time, certainly hold promise with respect to tracking disease evolution and responses to treatments on a scale not accessible before.”
A more immediate and comprehensive overview of a patient’s response to a treatment “could yield more rapid insights into the effectiveness of novel therapies tested in clinical trials,” said Dr. Gosselin. “This could have profound implications.”
Future digital devices may facilitate monitoring of patients in more remote communities, too, said Dr. Gosselin.
However, before these technologies can be introduced on a broad level, several outstanding issues will have to be addressed, the most important being the streams of data they generate, said Dr. Gosselin.
“This clearly has the potential to overwhelm neurologists in the assessment of their patients’ conditions,” he said. “Which information, and in which analyzed forms, truly provides meaningful insights into patients’ conditions will need to be identified, and this will take time.”
Privacy may be an issue, too, said Dr. Gosselin. Some patients may be less inclined to comply with a procedure “that can capture and record their life so extensively.”
And how health care insurance providers can interface with these comprehensive profiles of patients’ lives will also have to be considered, he said.
Dr. Graves has a provisional patent on the MSight device; has received research support from MMSS, Octave, Biogen EMD Serono, Novartis, ATARA Biotherapeutics, and ABM; has served on advisory boards for Bayer, Genentech, and TG therapeutic and a pediatric clinical trial steering committee for Novartis; and has consulted for Google. Dr. Gosselin reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO – A new wearable device detects, with a high degree of precision, various types of visual dysfunction, which eventually affects most patients with multiple sclerosis (MS). The device uses advanced digital technology to stimulate the retina and the occipital cortex while also stimulating the eye tracking system, and reports out this data, one of its developers, Jennifer Graves, MD, PhD, director of neuroimmunology research, University of California, San Diego, said in an interview.
“In one paradigm of testing, we can get both sets of information,” which eliminates the complicated equipment set-up used by neuro-ophthalmologists, and makes eye assessments more readily available, she said.
“We can make this accessible for more clinicians and more patients, even eventually having it in an emergency setting or an outpatient clinic setting.”
Dr. Graves discussed this and other next-generation digital tools at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Currently, patients with MS can use accelerometers that determine overall activity level and devices that detect heart rate variability. They can also access mobile apps that track symptoms and medication adherence.
Limited sensitivity of current tools
However, current tools used to determine disability in MS are limited. The classification of MS subtypes is largely retrospective, and the preferred Expanded Disability Status Scale (EDSS) is problematic, said Dr. Graves.
For example, she said, the EDSS lacks sensitivity to short-term changes, depends on ambulation, and only poorly captures upper-extremity disability. “We know our patients are experiencing change and we know the tools we have now aren’t capturing that.”
She used the example of a pianist who can no longer play well with her right hand, but this can’t be detected with current tools. A device that uses technology from the gaming and computer control industry “can quantify that” change, said Dr. Graves.
She added that . “Rather than having descriptive terms, these digital tools will help us quantitate change so we can take action.”
The new sensing devices use multiple sensors, including accelerometers, gyroscopes, and surface electrical signals in muscles to capture very precise temporal and textural information related to movement. Their development uses traditional signal processing as well as artificial intelligence approaches.
Dr. Graves’s device, the MSight, captures afferent and efferent visual function with a single mobile brain-computer interface.
At least 80% of patients with MS have some measurable dysfunction in the afferent system that oversees how light from the environment is turned into images in the brain, explained Dr. Graves. The efferent visual system that controls eye movements is also “profoundly impacted by MS” with, again, up to 80% of patients with MS experiencing related dysfunction, she said.
Her new visual system correlates with burden of MS disease, said Dr. Graves. “Having efferent and eye tracking problems correlates with overall disability and walking function.”
The information collected by this new device “tends to be really helpful even in people who don’t appear to be disabled with MS because it’s literally a window into the brain to let us see what’s happening,” said Dr. Graves.
She and her colleagues are testing the MSight device in clinical trials and have a provisional patent for it.
Finger and foot taps
Another device her team is developing detects minute changes over several months in finger and toe tap movements that are very difficult for the human eye to capture.
Dr. Graves reported on a cross sectional validation study of 17 patients with MS showing the foot and finger tap measures strongly correlated with the EDSS and patient-reported outcomes (P < .0001). A longitudinal analysis of 68 patients with MS found information on finger and foot taps distinguished those with progressive from those with relapsing MS.
“We found that in patients with progressive MS, the information in the signal we were capturing was changing, whereas someone with relapsing MS had a little bit of that but much less,” said Dr. Graves.
These and other novel, self-contained devices “will provide a set of neurological vital signs that we can put in the hands of clinicians and patients” with MS, as is currently being done in other specialties – for example, cardiology, said Dr. Graves.
Intriguing, exciting
In a comment, David Gosselin, PhD, associate professor, department of molecular medicine, Laval University, Quebec City, who cochaired the session featuring next-generation digital tools, said more sensitive monitoring technologies coming down the pipeline are “intriguing and exciting.”
While the devices are still in early development, “the eventual integration of such noninvasive technology that measures subtle limb muscle function has the potential to redefine clinical practice,” said Dr. Gosselin.
“The idea of sampling a patient’s ability to move about on a frequent basis, perhaps even daily, and to generate data profiles over time, certainly hold promise with respect to tracking disease evolution and responses to treatments on a scale not accessible before.”
A more immediate and comprehensive overview of a patient’s response to a treatment “could yield more rapid insights into the effectiveness of novel therapies tested in clinical trials,” said Dr. Gosselin. “This could have profound implications.”
Future digital devices may facilitate monitoring of patients in more remote communities, too, said Dr. Gosselin.
However, before these technologies can be introduced on a broad level, several outstanding issues will have to be addressed, the most important being the streams of data they generate, said Dr. Gosselin.
“This clearly has the potential to overwhelm neurologists in the assessment of their patients’ conditions,” he said. “Which information, and in which analyzed forms, truly provides meaningful insights into patients’ conditions will need to be identified, and this will take time.”
Privacy may be an issue, too, said Dr. Gosselin. Some patients may be less inclined to comply with a procedure “that can capture and record their life so extensively.”
And how health care insurance providers can interface with these comprehensive profiles of patients’ lives will also have to be considered, he said.
Dr. Graves has a provisional patent on the MSight device; has received research support from MMSS, Octave, Biogen EMD Serono, Novartis, ATARA Biotherapeutics, and ABM; has served on advisory boards for Bayer, Genentech, and TG therapeutic and a pediatric clinical trial steering committee for Novartis; and has consulted for Google. Dr. Gosselin reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACTRIMS FORUM 2023
MS looks homogeneous
SAN DIEGO – , rather than a mixture of conditions with different genetic or other causes, according to a new analysis. The work suggests that personalized therapy based on clinical characteristics is likely to be the best approach, rather than precision medicine based on molecular or other subtypes.
Think MS is heterogeneous? Think again
The work drew upon data from 22,000 individuals, 32,000 attacks, 156,000 EDSS scores, 250,000 observation years, and 110,000 treatment years recorded in the Swedish MS registry. The researchers examined distributions in age of onset, severity, and distribution of relapses. Among patients treated with one of 12 disease-modifying therapies, they examined patterns of EDSS progression, appearance of new lesions, and relapses.
“
Regardless of which clinical characteristic of the MS syndrome that I study, I find a uniform distribution with very few if any outliers. That argues that MS is likely to be a homogeneous condition with some variation, but it’s highly unlikely that MS is a mixture of different conditions masquerading as the same thing,” said Jan Hillert, MD, PhD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“There are big efforts out there trying to decipher the molecular basis of the MS syndrome, thinking that it’s a mixture of different things. And I would argue that our data very strongly argue against that,” said Dr. Hillert, who is a professor of neurology at Karolinska Institutet in Solna, Sweden.
Specific subtypes should produce individual groupings rather than a broad distribution. “If you have a multitude of factors, then this (finding of a broad distribution) is what you have. If you have a small number of strongly acting factors, like if there were genetic subgroups, then you would have a different distribution. So this is in line with the polygenic, complex nature of MS that we have been thinking about for many, many years, and which the genetics also support,” said Dr. Hillert.
The findings suggest that physicians should be emphasizing personalized treatment of MS based on factors like age, weight, disease activity and severity, disability, side effects, and other factors. “Personalized medicine I embrace, but the concept of precision medicine is naive. It’s not founded on any sound scientific evidence,” said Dr. Hillert.
An evolving definition
The conclusion is compelling, according to Patricia Coyle, MD, who was asked to comment on the study. “I have not seen this sort of analysis before. I think it doesn’t absolutely prove the case in talking about very small numbers, but it does make a very logical argument. This is not showing any meaningful large subgroups that you can call out,” said Dr. Coyle, who is a professor of neurology and director of the MS Comprehensive Care Center at Stonybrook Neurosciences Institute in New York.
“I think that it’s interesting, because we have routinely said we think this is heterogeneous, because no two patients are alike. But this is speaking against meaningful heterogeneity in MS. When you look at these sorts of statistical results, this is what you’d expect in a normal population, not in a disease where you might say, genetically, or molecularly, you could define significant subsets of individuals,” said Dr. Coyle.
The study isn’t the last word. “You would probably like to see some follow-up data, perhaps in other very large databases to make it more convincing, but I think you’re not hearing as many people talk about MS heterogeneity anymore. We know there’s a focal inflammatory component, we know there’s a neurodegenerative component. Both are present in all MS. People are even arguing that maybe it’s not meaningful to call out progressive and relapsing MS. I don’t agree with that, but I think the concept that there are meaningful subsets of patients is probably incorrect. [The idea that] one set is due to perhaps an infection, another might be molecular mimicry. ... Maybe that’s not the case at all,” said Dr. Coyle.
For example, some companies are looking into whether B cell depletion treatments might be more effective for one set of patients versus another. “The issue is, can you dissect out subsets where hitting B cells is really good and others where it doesn’t seem to matter? That really hasn’t [been successful],” said Dr. Coyle.
Dr. Hillert has served on scientific advisor boards for or received speaker’s fees from Biogen, Bristol Myers Squibb/Celgene, Janssen, Novartis, Teva, Merck KGaA, Sandoz, and Sanofi Genzyme. He has received research support from Biogen, Bristol Myers Squibb/Celgene, Merck, Janssen, Novartis, Roche, and Sanofi-Genzyme. Dr. Coyle has consulted for or received speaker fees from Accordant, Biogen, Bristol Myers Squibb, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly and Company, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics. She has received research support from Actelion, Alkermes, Celgene, CorEvitas, Genentech/Roche, Janssen, MedDay, NINDS, Novartis, and Sanofi Genzyme.
SAN DIEGO – , rather than a mixture of conditions with different genetic or other causes, according to a new analysis. The work suggests that personalized therapy based on clinical characteristics is likely to be the best approach, rather than precision medicine based on molecular or other subtypes.
Think MS is heterogeneous? Think again
The work drew upon data from 22,000 individuals, 32,000 attacks, 156,000 EDSS scores, 250,000 observation years, and 110,000 treatment years recorded in the Swedish MS registry. The researchers examined distributions in age of onset, severity, and distribution of relapses. Among patients treated with one of 12 disease-modifying therapies, they examined patterns of EDSS progression, appearance of new lesions, and relapses.
“
Regardless of which clinical characteristic of the MS syndrome that I study, I find a uniform distribution with very few if any outliers. That argues that MS is likely to be a homogeneous condition with some variation, but it’s highly unlikely that MS is a mixture of different conditions masquerading as the same thing,” said Jan Hillert, MD, PhD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“There are big efforts out there trying to decipher the molecular basis of the MS syndrome, thinking that it’s a mixture of different things. And I would argue that our data very strongly argue against that,” said Dr. Hillert, who is a professor of neurology at Karolinska Institutet in Solna, Sweden.
Specific subtypes should produce individual groupings rather than a broad distribution. “If you have a multitude of factors, then this (finding of a broad distribution) is what you have. If you have a small number of strongly acting factors, like if there were genetic subgroups, then you would have a different distribution. So this is in line with the polygenic, complex nature of MS that we have been thinking about for many, many years, and which the genetics also support,” said Dr. Hillert.
The findings suggest that physicians should be emphasizing personalized treatment of MS based on factors like age, weight, disease activity and severity, disability, side effects, and other factors. “Personalized medicine I embrace, but the concept of precision medicine is naive. It’s not founded on any sound scientific evidence,” said Dr. Hillert.
An evolving definition
The conclusion is compelling, according to Patricia Coyle, MD, who was asked to comment on the study. “I have not seen this sort of analysis before. I think it doesn’t absolutely prove the case in talking about very small numbers, but it does make a very logical argument. This is not showing any meaningful large subgroups that you can call out,” said Dr. Coyle, who is a professor of neurology and director of the MS Comprehensive Care Center at Stonybrook Neurosciences Institute in New York.
“I think that it’s interesting, because we have routinely said we think this is heterogeneous, because no two patients are alike. But this is speaking against meaningful heterogeneity in MS. When you look at these sorts of statistical results, this is what you’d expect in a normal population, not in a disease where you might say, genetically, or molecularly, you could define significant subsets of individuals,” said Dr. Coyle.
The study isn’t the last word. “You would probably like to see some follow-up data, perhaps in other very large databases to make it more convincing, but I think you’re not hearing as many people talk about MS heterogeneity anymore. We know there’s a focal inflammatory component, we know there’s a neurodegenerative component. Both are present in all MS. People are even arguing that maybe it’s not meaningful to call out progressive and relapsing MS. I don’t agree with that, but I think the concept that there are meaningful subsets of patients is probably incorrect. [The idea that] one set is due to perhaps an infection, another might be molecular mimicry. ... Maybe that’s not the case at all,” said Dr. Coyle.
For example, some companies are looking into whether B cell depletion treatments might be more effective for one set of patients versus another. “The issue is, can you dissect out subsets where hitting B cells is really good and others where it doesn’t seem to matter? That really hasn’t [been successful],” said Dr. Coyle.
Dr. Hillert has served on scientific advisor boards for or received speaker’s fees from Biogen, Bristol Myers Squibb/Celgene, Janssen, Novartis, Teva, Merck KGaA, Sandoz, and Sanofi Genzyme. He has received research support from Biogen, Bristol Myers Squibb/Celgene, Merck, Janssen, Novartis, Roche, and Sanofi-Genzyme. Dr. Coyle has consulted for or received speaker fees from Accordant, Biogen, Bristol Myers Squibb, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly and Company, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics. She has received research support from Actelion, Alkermes, Celgene, CorEvitas, Genentech/Roche, Janssen, MedDay, NINDS, Novartis, and Sanofi Genzyme.
SAN DIEGO – , rather than a mixture of conditions with different genetic or other causes, according to a new analysis. The work suggests that personalized therapy based on clinical characteristics is likely to be the best approach, rather than precision medicine based on molecular or other subtypes.
Think MS is heterogeneous? Think again
The work drew upon data from 22,000 individuals, 32,000 attacks, 156,000 EDSS scores, 250,000 observation years, and 110,000 treatment years recorded in the Swedish MS registry. The researchers examined distributions in age of onset, severity, and distribution of relapses. Among patients treated with one of 12 disease-modifying therapies, they examined patterns of EDSS progression, appearance of new lesions, and relapses.
“
Regardless of which clinical characteristic of the MS syndrome that I study, I find a uniform distribution with very few if any outliers. That argues that MS is likely to be a homogeneous condition with some variation, but it’s highly unlikely that MS is a mixture of different conditions masquerading as the same thing,” said Jan Hillert, MD, PhD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“There are big efforts out there trying to decipher the molecular basis of the MS syndrome, thinking that it’s a mixture of different things. And I would argue that our data very strongly argue against that,” said Dr. Hillert, who is a professor of neurology at Karolinska Institutet in Solna, Sweden.
Specific subtypes should produce individual groupings rather than a broad distribution. “If you have a multitude of factors, then this (finding of a broad distribution) is what you have. If you have a small number of strongly acting factors, like if there were genetic subgroups, then you would have a different distribution. So this is in line with the polygenic, complex nature of MS that we have been thinking about for many, many years, and which the genetics also support,” said Dr. Hillert.
The findings suggest that physicians should be emphasizing personalized treatment of MS based on factors like age, weight, disease activity and severity, disability, side effects, and other factors. “Personalized medicine I embrace, but the concept of precision medicine is naive. It’s not founded on any sound scientific evidence,” said Dr. Hillert.
An evolving definition
The conclusion is compelling, according to Patricia Coyle, MD, who was asked to comment on the study. “I have not seen this sort of analysis before. I think it doesn’t absolutely prove the case in talking about very small numbers, but it does make a very logical argument. This is not showing any meaningful large subgroups that you can call out,” said Dr. Coyle, who is a professor of neurology and director of the MS Comprehensive Care Center at Stonybrook Neurosciences Institute in New York.
“I think that it’s interesting, because we have routinely said we think this is heterogeneous, because no two patients are alike. But this is speaking against meaningful heterogeneity in MS. When you look at these sorts of statistical results, this is what you’d expect in a normal population, not in a disease where you might say, genetically, or molecularly, you could define significant subsets of individuals,” said Dr. Coyle.
The study isn’t the last word. “You would probably like to see some follow-up data, perhaps in other very large databases to make it more convincing, but I think you’re not hearing as many people talk about MS heterogeneity anymore. We know there’s a focal inflammatory component, we know there’s a neurodegenerative component. Both are present in all MS. People are even arguing that maybe it’s not meaningful to call out progressive and relapsing MS. I don’t agree with that, but I think the concept that there are meaningful subsets of patients is probably incorrect. [The idea that] one set is due to perhaps an infection, another might be molecular mimicry. ... Maybe that’s not the case at all,” said Dr. Coyle.
For example, some companies are looking into whether B cell depletion treatments might be more effective for one set of patients versus another. “The issue is, can you dissect out subsets where hitting B cells is really good and others where it doesn’t seem to matter? That really hasn’t [been successful],” said Dr. Coyle.
Dr. Hillert has served on scientific advisor boards for or received speaker’s fees from Biogen, Bristol Myers Squibb/Celgene, Janssen, Novartis, Teva, Merck KGaA, Sandoz, and Sanofi Genzyme. He has received research support from Biogen, Bristol Myers Squibb/Celgene, Merck, Janssen, Novartis, Roche, and Sanofi-Genzyme. Dr. Coyle has consulted for or received speaker fees from Accordant, Biogen, Bristol Myers Squibb, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly and Company, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics. She has received research support from Actelion, Alkermes, Celgene, CorEvitas, Genentech/Roche, Janssen, MedDay, NINDS, Novartis, and Sanofi Genzyme.
At ACTRIMS FORUM 2023
Portable MRI has potential for MS
, suggesting that it could have potential for use in screening high-risk patients.
Although previous studies had shown that the approach could hold up to high-field MRI, the new study was a blind comparison in which raters did not have access to the high-field images.
In addition to portability, the device has potential advantages over high-field MRI, including low cost and no need for high-field physical shielding. It could be used for point-of-care testing, especially in remote or low-resource areas. It does not produce ionizing radiation, and has been used in intensive care units and pediatric facilities.
Advantages and limitations
The device isn’t ready for general use in MS. It performed well in periventricular lesions but less well in other areas. Ongoing research could improve its performance, including multiplanar imaging and image analysis.
“I think it still needs some work, but to me if it’s less expensive it will be particularly better for third-world countries and that sort of place, or possibly for use in the field in the United States or in North America. If something is detected, you can then bring the person in for a better scan, but I don’t know how sensitive it is – how much pathology you might miss. But in countries where there are no MRIs, it’s certainly better than nothing,” said Anne Cross, MD, who comoderated the session at the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study was presented.
She also noted that the device is potentially safer than high-field MRI. “I don’t think it would be something insurance companies or patients would want to pay $1,000 for when they could get a better scan somewhere, but it’ll get better,” said Dr. Cross, who is a professor of neurology and chair of neuroimmunology at Washington University in St. Louis.
How reliable are low-field images?
In previous work, in which evaluators compared the two scans side by side, the researchers showed in 36 patients that the device performed well, compared with a 64mT scanner. “When we look at tandem evaluations, we can identify dissemination in space in 80%. When a patient has at least one lesion that is larger than 4 millimeters in its largest diameter, we are able to detect it in the ultralow field MRI with 100% sensitivity. The open question here is, what is the diagnostic utility of these scanners when we don’t have any information about the high-field images?” said Serhat Okar, MD, during his presentation of the study. Dr. Okar is a neurologist and postdoctoral researcher at the National Institutes of Health.
To answer that question, the researchers asked two raters to examine scans from the low-field MRI, but only an independent party evaluator had access to both scans.
The study included 55 MS patients who were seen for either clinical or research purposes. The average age was 41 years, and 43 patients were female. Two neuroradiologists served as scan raters. Rater 1 had 17 years of experience, and rater 2 had 9 years of experience. They each conducted assessments for periventricular, juxtacortical, infratentorial, deep white matter, and deep gray matter lesions, as well as dissemination in space. They marked the scan and filled out an online form with number of observed lesions and whether they observed dissemination in space, with responses checked against a high-field image by an independent neuroradiologist for true positive and false positive findings.
There was significant discordance between raters for observation of dissemination in space, with rater 1 reporting 81% positivity and reader 2, 49%. False positive analyses revealed a difference in their approaches: Rater 1 was more conservative in marking lesions, which led to fewer true positive and fewer false positive findings. Both raters had good performance in the periventricular lesions with similar, low rates of false positives.
Other areas were a different story. Both raters found a greater number of true positive and false positive areas in the juxtacortical, deep white matter, and deep gray matter areas.
The study was funded by Hyperfine. Dr. Okar and Dr. Cross have no relevant financial disclosures.
, suggesting that it could have potential for use in screening high-risk patients.
Although previous studies had shown that the approach could hold up to high-field MRI, the new study was a blind comparison in which raters did not have access to the high-field images.
In addition to portability, the device has potential advantages over high-field MRI, including low cost and no need for high-field physical shielding. It could be used for point-of-care testing, especially in remote or low-resource areas. It does not produce ionizing radiation, and has been used in intensive care units and pediatric facilities.
Advantages and limitations
The device isn’t ready for general use in MS. It performed well in periventricular lesions but less well in other areas. Ongoing research could improve its performance, including multiplanar imaging and image analysis.
“I think it still needs some work, but to me if it’s less expensive it will be particularly better for third-world countries and that sort of place, or possibly for use in the field in the United States or in North America. If something is detected, you can then bring the person in for a better scan, but I don’t know how sensitive it is – how much pathology you might miss. But in countries where there are no MRIs, it’s certainly better than nothing,” said Anne Cross, MD, who comoderated the session at the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study was presented.
She also noted that the device is potentially safer than high-field MRI. “I don’t think it would be something insurance companies or patients would want to pay $1,000 for when they could get a better scan somewhere, but it’ll get better,” said Dr. Cross, who is a professor of neurology and chair of neuroimmunology at Washington University in St. Louis.
How reliable are low-field images?
In previous work, in which evaluators compared the two scans side by side, the researchers showed in 36 patients that the device performed well, compared with a 64mT scanner. “When we look at tandem evaluations, we can identify dissemination in space in 80%. When a patient has at least one lesion that is larger than 4 millimeters in its largest diameter, we are able to detect it in the ultralow field MRI with 100% sensitivity. The open question here is, what is the diagnostic utility of these scanners when we don’t have any information about the high-field images?” said Serhat Okar, MD, during his presentation of the study. Dr. Okar is a neurologist and postdoctoral researcher at the National Institutes of Health.
To answer that question, the researchers asked two raters to examine scans from the low-field MRI, but only an independent party evaluator had access to both scans.
The study included 55 MS patients who were seen for either clinical or research purposes. The average age was 41 years, and 43 patients were female. Two neuroradiologists served as scan raters. Rater 1 had 17 years of experience, and rater 2 had 9 years of experience. They each conducted assessments for periventricular, juxtacortical, infratentorial, deep white matter, and deep gray matter lesions, as well as dissemination in space. They marked the scan and filled out an online form with number of observed lesions and whether they observed dissemination in space, with responses checked against a high-field image by an independent neuroradiologist for true positive and false positive findings.
There was significant discordance between raters for observation of dissemination in space, with rater 1 reporting 81% positivity and reader 2, 49%. False positive analyses revealed a difference in their approaches: Rater 1 was more conservative in marking lesions, which led to fewer true positive and fewer false positive findings. Both raters had good performance in the periventricular lesions with similar, low rates of false positives.
Other areas were a different story. Both raters found a greater number of true positive and false positive areas in the juxtacortical, deep white matter, and deep gray matter areas.
The study was funded by Hyperfine. Dr. Okar and Dr. Cross have no relevant financial disclosures.
, suggesting that it could have potential for use in screening high-risk patients.
Although previous studies had shown that the approach could hold up to high-field MRI, the new study was a blind comparison in which raters did not have access to the high-field images.
In addition to portability, the device has potential advantages over high-field MRI, including low cost and no need for high-field physical shielding. It could be used for point-of-care testing, especially in remote or low-resource areas. It does not produce ionizing radiation, and has been used in intensive care units and pediatric facilities.
Advantages and limitations
The device isn’t ready for general use in MS. It performed well in periventricular lesions but less well in other areas. Ongoing research could improve its performance, including multiplanar imaging and image analysis.
“I think it still needs some work, but to me if it’s less expensive it will be particularly better for third-world countries and that sort of place, or possibly for use in the field in the United States or in North America. If something is detected, you can then bring the person in for a better scan, but I don’t know how sensitive it is – how much pathology you might miss. But in countries where there are no MRIs, it’s certainly better than nothing,” said Anne Cross, MD, who comoderated the session at the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study was presented.
She also noted that the device is potentially safer than high-field MRI. “I don’t think it would be something insurance companies or patients would want to pay $1,000 for when they could get a better scan somewhere, but it’ll get better,” said Dr. Cross, who is a professor of neurology and chair of neuroimmunology at Washington University in St. Louis.
How reliable are low-field images?
In previous work, in which evaluators compared the two scans side by side, the researchers showed in 36 patients that the device performed well, compared with a 64mT scanner. “When we look at tandem evaluations, we can identify dissemination in space in 80%. When a patient has at least one lesion that is larger than 4 millimeters in its largest diameter, we are able to detect it in the ultralow field MRI with 100% sensitivity. The open question here is, what is the diagnostic utility of these scanners when we don’t have any information about the high-field images?” said Serhat Okar, MD, during his presentation of the study. Dr. Okar is a neurologist and postdoctoral researcher at the National Institutes of Health.
To answer that question, the researchers asked two raters to examine scans from the low-field MRI, but only an independent party evaluator had access to both scans.
The study included 55 MS patients who were seen for either clinical or research purposes. The average age was 41 years, and 43 patients were female. Two neuroradiologists served as scan raters. Rater 1 had 17 years of experience, and rater 2 had 9 years of experience. They each conducted assessments for periventricular, juxtacortical, infratentorial, deep white matter, and deep gray matter lesions, as well as dissemination in space. They marked the scan and filled out an online form with number of observed lesions and whether they observed dissemination in space, with responses checked against a high-field image by an independent neuroradiologist for true positive and false positive findings.
There was significant discordance between raters for observation of dissemination in space, with rater 1 reporting 81% positivity and reader 2, 49%. False positive analyses revealed a difference in their approaches: Rater 1 was more conservative in marking lesions, which led to fewer true positive and fewer false positive findings. Both raters had good performance in the periventricular lesions with similar, low rates of false positives.
Other areas were a different story. Both raters found a greater number of true positive and false positive areas in the juxtacortical, deep white matter, and deep gray matter areas.
The study was funded by Hyperfine. Dr. Okar and Dr. Cross have no relevant financial disclosures.
AT ACTRIMS FORUM 2023
A better MS measure?
“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.
“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.
Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).
Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.
“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
Technology provides more sensitive, but more complex data
Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.
The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
Granular gait analysis
Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.
There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R2 = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R2 = 0.63); double support (R2 = 0.74); cadence (R2 = 0.56); and gait variability index (R2 = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R2 = 0.53); double support (R2 = 0.30); cadence (R2 = 0.43); and gait variability index (R2 = 0.46).
TUG values were significantly associated with gait parameters during PWS: velocity (R2 = 0.71); double support (R2 = 0.75); cadence (R2 = 0.43); gait variability index (R2 = 0.45); and walk ratio (R2 = 0.06). During dual task walking, TUG values were significantly associated with velocity (R2 = 0.55), double support (R2 = 0.21), cadence (R2 = 0.45), and gait variability index (R2 = 0.39).
“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.
Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.
“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.
“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.
Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).
Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.
“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
Technology provides more sensitive, but more complex data
Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.
The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
Granular gait analysis
Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.
There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R2 = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R2 = 0.63); double support (R2 = 0.74); cadence (R2 = 0.56); and gait variability index (R2 = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R2 = 0.53); double support (R2 = 0.30); cadence (R2 = 0.43); and gait variability index (R2 = 0.46).
TUG values were significantly associated with gait parameters during PWS: velocity (R2 = 0.71); double support (R2 = 0.75); cadence (R2 = 0.43); gait variability index (R2 = 0.45); and walk ratio (R2 = 0.06). During dual task walking, TUG values were significantly associated with velocity (R2 = 0.55), double support (R2 = 0.21), cadence (R2 = 0.45), and gait variability index (R2 = 0.39).
“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.
Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.
“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.
“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.
Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).
Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.
“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
Technology provides more sensitive, but more complex data
Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.
The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
Granular gait analysis
Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.
There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R2 = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R2 = 0.63); double support (R2 = 0.74); cadence (R2 = 0.56); and gait variability index (R2 = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R2 = 0.53); double support (R2 = 0.30); cadence (R2 = 0.43); and gait variability index (R2 = 0.46).
TUG values were significantly associated with gait parameters during PWS: velocity (R2 = 0.71); double support (R2 = 0.75); cadence (R2 = 0.43); gait variability index (R2 = 0.45); and walk ratio (R2 = 0.06). During dual task walking, TUG values were significantly associated with velocity (R2 = 0.55), double support (R2 = 0.21), cadence (R2 = 0.45), and gait variability index (R2 = 0.39).
“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.
Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.
FROM ACTRIMS FORUM 2023
Cutting calories may benefit cognition in MS
SAN DIEGO – , new research suggests.
Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.
Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
High adherence rate
Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.
The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.
Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.
In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.
Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.
Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.
Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.
“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
Maintain healthy weight
The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.
There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.
Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.
However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.
She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
Superb study
Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.
“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.
Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.
The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – , new research suggests.
Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.
Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
High adherence rate
Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.
The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.
Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.
In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.
Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.
Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.
Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.
“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
Maintain healthy weight
The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.
There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.
Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.
However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.
She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
Superb study
Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.
“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.
Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.
The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – , new research suggests.
Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.
Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
High adherence rate
Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.
The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.
Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.
In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.
Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.
Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.
Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.
“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
Maintain healthy weight
The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.
There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.
Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.
However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.
She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
Superb study
Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.
“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.
Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.
The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ACTRIMS FORUM 2023
High level of psychiatric morbidity in prodromal MS
SAN DIEGO – new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.
These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.
With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Psychiatric morbidity during the prodromal phase of MS
Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.
Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.
The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.
The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.
The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.
The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.
Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.
It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.
In addition to psychiatric complaints, MS patients experience other symptoms, including pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.
Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.
He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
When does MS start?
Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.
He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”
Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.
The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.
These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.
With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Psychiatric morbidity during the prodromal phase of MS
Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.
Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.
The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.
The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.
The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.
The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.
Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.
It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.
In addition to psychiatric complaints, MS patients experience other symptoms, including pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.
Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.
He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
When does MS start?
Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.
He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”
Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.
The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.
These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.
With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Psychiatric morbidity during the prodromal phase of MS
Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.
Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.
The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.
The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.
The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.
The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.
Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.
It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.
In addition to psychiatric complaints, MS patients experience other symptoms, including pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.
Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.
He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
When does MS start?
Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.
He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”
Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.
The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ACTRIMS FORUM 2023
MOGAD: Immunotherapy predicts fewer relapses
SAN DIEGO – The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.
MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Predicting which patients will relapse
“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.
The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).
However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
The most effective treatment for relapsing MOGAD
In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.
Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.
Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.
He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.
“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
‘A good beginning’
The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.
“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.
Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.
SAN DIEGO – The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.
MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Predicting which patients will relapse
“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.
The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).
However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
The most effective treatment for relapsing MOGAD
In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.
Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.
Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.
He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.
“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
‘A good beginning’
The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.
“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.
Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.
SAN DIEGO – The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.
MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Predicting which patients will relapse
“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.
The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).
However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
The most effective treatment for relapsing MOGAD
In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.
Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.
Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.
He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.
“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
‘A good beginning’
The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.
“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.
Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.
At ACTRIMS FORUM 2023
To prevent MS, should we target EBV?
SAN DIEGO – Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.
That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.
At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
Reducing the risk of MS by targeting EBV
Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.
EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.
Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.
He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.
The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.
Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.
Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
Does EBV infection even matter?
In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.
Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.
Still, he is unconvinced that EBV is solely responsible for MS. “I think it’s hard to draw a straight line between EBV and MS as one might with HPV [human papillomavirus] and cervical cancer. For example, we know that EBV accounts for more than 1% of all cancers, and EBV can also cause other autoimmune diseases such as lupus and Sjogren’s, so it’s complicated. And MS of course has genetic susceptibility that’s not limited to the major histocompatibility complex (MHC) genes that are associated with presenting viral peptides,” said Dr. Calabresi.
Evidence relating MS vulnerability to other genetic and environmental factors, including diet, sunlight, smoking, and even pollution, calls into question a direct causal relationship between EBV and MS, he said.
The age prevalence of EBV would complicate efforts to eradicate it. Seroprevalence is 55% by age 5-11 and 75% among university students. “This is important because the duration of the vaccine response–induced protection in young seronegative children is not lengthy. Vaccinated individuals may become susceptible to natural infection at an age where the consequences of infection are more severe, especially leading to infectious mononucleosis, and hopefully not MS. This then raises the issue of the need for boosters, which we’re all well aware of during the COVID pandemic. This may be a problem, especially in young adults due to noncompliance,” said Dr. Calabresi.
He pointed out that not all vaccine attempts went well. In the 1960s, early respiratory syncytial virus (RSV) vaccines caused enhanced respiratory disease and 2 deaths. “We need to be careful when we think about targeting healthy at-risk young people,” said Dr. Calabresi.
Rather than pursue vaccination, Dr. Calabresi favors research into EBV latency in B cells as well as how EBV-infected B cells may cause or exacerbate MS, with the hopes of developing interventions. “It’s tempting to speculate that the success of the anti-CD 20 monoclonal antibody therapies is related to depletion of EBV infected B cells. In fact, I think that may be the case,” he said.
Dr. Cohen has no relevant financial disclosures. Dr. Calabresi has served on a scientific advisory board or data monitoring board for Biogen and Disarm Therapeutics.
SAN DIEGO – Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.
That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.
At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
Reducing the risk of MS by targeting EBV
Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.
EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.
Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.
He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.
The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.
Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.
Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
Does EBV infection even matter?
In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.
Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.
Still, he is unconvinced that EBV is solely responsible for MS. “I think it’s hard to draw a straight line between EBV and MS as one might with HPV [human papillomavirus] and cervical cancer. For example, we know that EBV accounts for more than 1% of all cancers, and EBV can also cause other autoimmune diseases such as lupus and Sjogren’s, so it’s complicated. And MS of course has genetic susceptibility that’s not limited to the major histocompatibility complex (MHC) genes that are associated with presenting viral peptides,” said Dr. Calabresi.
Evidence relating MS vulnerability to other genetic and environmental factors, including diet, sunlight, smoking, and even pollution, calls into question a direct causal relationship between EBV and MS, he said.
The age prevalence of EBV would complicate efforts to eradicate it. Seroprevalence is 55% by age 5-11 and 75% among university students. “This is important because the duration of the vaccine response–induced protection in young seronegative children is not lengthy. Vaccinated individuals may become susceptible to natural infection at an age where the consequences of infection are more severe, especially leading to infectious mononucleosis, and hopefully not MS. This then raises the issue of the need for boosters, which we’re all well aware of during the COVID pandemic. This may be a problem, especially in young adults due to noncompliance,” said Dr. Calabresi.
He pointed out that not all vaccine attempts went well. In the 1960s, early respiratory syncytial virus (RSV) vaccines caused enhanced respiratory disease and 2 deaths. “We need to be careful when we think about targeting healthy at-risk young people,” said Dr. Calabresi.
Rather than pursue vaccination, Dr. Calabresi favors research into EBV latency in B cells as well as how EBV-infected B cells may cause or exacerbate MS, with the hopes of developing interventions. “It’s tempting to speculate that the success of the anti-CD 20 monoclonal antibody therapies is related to depletion of EBV infected B cells. In fact, I think that may be the case,” he said.
Dr. Cohen has no relevant financial disclosures. Dr. Calabresi has served on a scientific advisory board or data monitoring board for Biogen and Disarm Therapeutics.
SAN DIEGO – Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.
That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.
At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
Reducing the risk of MS by targeting EBV
Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.
EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.
Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.
He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.
The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.
Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.
Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
Does EBV infection even matter?
In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.
Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.
Still, he is unconvinced that EBV is solely responsible for MS. “I think it’s hard to draw a straight line between EBV and MS as one might with HPV [human papillomavirus] and cervical cancer. For example, we know that EBV accounts for more than 1% of all cancers, and EBV can also cause other autoimmune diseases such as lupus and Sjogren’s, so it’s complicated. And MS of course has genetic susceptibility that’s not limited to the major histocompatibility complex (MHC) genes that are associated with presenting viral peptides,” said Dr. Calabresi.
Evidence relating MS vulnerability to other genetic and environmental factors, including diet, sunlight, smoking, and even pollution, calls into question a direct causal relationship between EBV and MS, he said.
The age prevalence of EBV would complicate efforts to eradicate it. Seroprevalence is 55% by age 5-11 and 75% among university students. “This is important because the duration of the vaccine response–induced protection in young seronegative children is not lengthy. Vaccinated individuals may become susceptible to natural infection at an age where the consequences of infection are more severe, especially leading to infectious mononucleosis, and hopefully not MS. This then raises the issue of the need for boosters, which we’re all well aware of during the COVID pandemic. This may be a problem, especially in young adults due to noncompliance,” said Dr. Calabresi.
He pointed out that not all vaccine attempts went well. In the 1960s, early respiratory syncytial virus (RSV) vaccines caused enhanced respiratory disease and 2 deaths. “We need to be careful when we think about targeting healthy at-risk young people,” said Dr. Calabresi.
Rather than pursue vaccination, Dr. Calabresi favors research into EBV latency in B cells as well as how EBV-infected B cells may cause or exacerbate MS, with the hopes of developing interventions. “It’s tempting to speculate that the success of the anti-CD 20 monoclonal antibody therapies is related to depletion of EBV infected B cells. In fact, I think that may be the case,” he said.
Dr. Cohen has no relevant financial disclosures. Dr. Calabresi has served on a scientific advisory board or data monitoring board for Biogen and Disarm Therapeutics.
FROM ACTRIMS FORUM 2023
Differential diagnosis in MS: What to watch for
SAN DIEGO –
The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Mimics and red flags
Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.
Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.
These and other red flags should prompt a careful look to get the right diagnosis.
Earlier diagnosis = better outcomes
“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.
“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
Look for patterns and imaging clues
Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.
Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”
Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
Common mistakes
MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”
Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.
SAN DIEGO –
The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Mimics and red flags
Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.
Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.
These and other red flags should prompt a careful look to get the right diagnosis.
Earlier diagnosis = better outcomes
“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.
“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
Look for patterns and imaging clues
Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.
Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”
Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
Common mistakes
MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”
Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.
SAN DIEGO –
The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Mimics and red flags
Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.
Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.
These and other red flags should prompt a careful look to get the right diagnosis.
Earlier diagnosis = better outcomes
“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.
“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
Look for patterns and imaging clues
Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.
Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”
Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
Common mistakes
MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”
Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.
FROM ACTRIMS FORUM 2023