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Tastier chocolate may be healthier chocolate
Chocolate: Now part of a well-balanced diet
Asking if someone loves chocolate is like asking if they love breathing. It’s really not a question that needs to be asked. The thing with chocolate, however, is that most people who love chocolate actually love sugar, since your typical milk chocolate contains only about 30% cacao. The rest, of course, is sugar.
Now, dark chocolate is actually kind of good for you since it contains beneficial flavonoids and less sugar. But that healthiness comes at a cost: Dark chocolate is quite bitter, and gets more so as the cacao content rises, to the point where 100% cacao chocolate is very nearly inedible. That’s the chocolate conundrum, the healthier it is, the worse it tastes. But what if there’s another way? What if you can have tasty chocolate that’s good for you?
That’s the question a group of researchers from Penn State University dared to ask. The secret, they discovered, is to subject the cacao beans to extra-intense roasting. We’re not sure how screaming insults at a bunch of beans will help, but if science says so ... YOU USELESS LUMP OF BARELY EDIBLE FOOD! HOW DARE YOU EXIST!
Oh, not that kind of roasting. Oops.
For their study, the researchers made 27 unsweetened chocolates, prepared using various cacao bean roasting times and temperatures, and served them to volunteers. Those volunteers reported that chocolates made with cacao beans roasted more intensely (such as 20 minutes at 340° F, 80 min at 275° F, and 54 min at 304° F) were far more acceptable than were chocolates prepared with raw or lightly roasted cacao beans.
The implications of healthy yet tasty chocolate are obvious: Master the chocolate and you’ll make millions. Imagine a future where parents say to their kids: “Don’t forget to eat your chocolate.” So, we’re off to do some cooking. Don’t want Hershey to make all the money off of this revelation.
The villain hiding in dairy for some MS patients
For some of us, lactose can be a real heartbreaker when it comes to dairy consumption, but for people with multiple sclerosis (MS) there’s another villain they may also have to face that can make their symptoms worse.
Physicians at the Institute of Anatomy at University Hospital Bonn (Germany) were getting so many complaints from patients with MS about how much worse they felt about after having cheese, yogurt, and milk that they decided to get to the bottom of it. The culprit, it seems, is casein, a protein specifically found in cow’s milk.
The researchers injected mice with various proteins found in cow’s milk and found perforated myelin sheaths in those given casein. In MS, the patient’s own immune system destroys that sheath, which leads to paresthesia, vision problems, and movement disorders.
“The body’s defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin, “ said Rittika Chunder, a postdoctoral fellow at the University of Bonn. How? Apparently it’s all a big misunderstanding.
While looking at molecules needed for myelin production, the researchers came across MAG, which is very similar to casein, which is a problem when patients with MS are allergic to casein. After they have dairy products, the B-cell squad gets called in to clean up the evil twin, casein, but can’t differentiate it from the good twin, MAG, so it all gets a wash and the myelin sheath suffers.
Since this happens only to patients with MS who have a casein allergy, the researchers advise them to stay away from milk, yogurt, or cottage cheese while they work on a self-test to check if patients carry the antibodies.
A small price to pay, perhaps, to stop a villainous evil twin.
You would even say it glows
If you’re anything like us – and we think you are since you’re reading this – you’ve been asking yourself: Are there any common medications in my house that will make good radiation sensors?
Not that anyone needs to worry about excess radiation or anything. Far from it. We were just wondering.
It just so happens that Anna Mrozik and Paweł Bilski, both of the Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) in Kraków, Poland, were wondering the same thing: “During an uncontrolled release of radiation, it is highly unlikely that members of the public will be equipped with personal radiation dose monitors.”
People would need to use something they had lying around the house. A smartphone would work, the investigators explained in a statement from the IFJ PAN, but the process of converting one to radiation-sensor duty, which involves dismantling it and breaking the display glass, “is laborious and time-consuming [and] the destruction of a valuable and useful device does not seem to be the optimal solution.”
Naturally, they turned to drugs. The key, in this case, is optically stimulated luminescence. They needed to find materials that would glow with greater intensity as the radiation dose increased. Turns out that ibuprofen- and paracetamol-based painkillers fit the bill quite nicely, although aspirin also works.
It’s not known exactly which substance is causing the luminescence, but rest assured, the “physicists from the IFJ PAN intend to identify it.”
This is why you don’t interrupt someone using headphones
There’s nothing like taking a nice relaxing walk with your headphones. Whether you’re listening to a podcast or a song or talking on the phone, it’s an escape from reality that makes you feel like you’re completely in tune with what you’re listening to.
According to a new study, headphones, as opposed to speakers, make people feel more connected to what they are listening to. Data collected from more than 4,000 people showed that listening with headphones makes more of an impact than listening to speakers.
“Headphones produce a phenomenon called in-head localization, which makes the speaker sound as if they’re inside your head,” study coauthor On Amir of the University of California, San Diego, said in a statement. Because of this, people feel like the speakers are close to them and there’s more of a sense of empathy for the speakers and the listener is more likely to be swayed toward the ideas of the speaker.
These findings could lead to more efficient training programs, online work, and advertising, the investigators suggested.
We now finally understand why people get so mad when they have to take out their headphones to answer or talk to us. We ruined a satisfying moment going on in their brains.
Chocolate: Now part of a well-balanced diet
Asking if someone loves chocolate is like asking if they love breathing. It’s really not a question that needs to be asked. The thing with chocolate, however, is that most people who love chocolate actually love sugar, since your typical milk chocolate contains only about 30% cacao. The rest, of course, is sugar.
Now, dark chocolate is actually kind of good for you since it contains beneficial flavonoids and less sugar. But that healthiness comes at a cost: Dark chocolate is quite bitter, and gets more so as the cacao content rises, to the point where 100% cacao chocolate is very nearly inedible. That’s the chocolate conundrum, the healthier it is, the worse it tastes. But what if there’s another way? What if you can have tasty chocolate that’s good for you?
That’s the question a group of researchers from Penn State University dared to ask. The secret, they discovered, is to subject the cacao beans to extra-intense roasting. We’re not sure how screaming insults at a bunch of beans will help, but if science says so ... YOU USELESS LUMP OF BARELY EDIBLE FOOD! HOW DARE YOU EXIST!
Oh, not that kind of roasting. Oops.
For their study, the researchers made 27 unsweetened chocolates, prepared using various cacao bean roasting times and temperatures, and served them to volunteers. Those volunteers reported that chocolates made with cacao beans roasted more intensely (such as 20 minutes at 340° F, 80 min at 275° F, and 54 min at 304° F) were far more acceptable than were chocolates prepared with raw or lightly roasted cacao beans.
The implications of healthy yet tasty chocolate are obvious: Master the chocolate and you’ll make millions. Imagine a future where parents say to their kids: “Don’t forget to eat your chocolate.” So, we’re off to do some cooking. Don’t want Hershey to make all the money off of this revelation.
The villain hiding in dairy for some MS patients
For some of us, lactose can be a real heartbreaker when it comes to dairy consumption, but for people with multiple sclerosis (MS) there’s another villain they may also have to face that can make their symptoms worse.
Physicians at the Institute of Anatomy at University Hospital Bonn (Germany) were getting so many complaints from patients with MS about how much worse they felt about after having cheese, yogurt, and milk that they decided to get to the bottom of it. The culprit, it seems, is casein, a protein specifically found in cow’s milk.
The researchers injected mice with various proteins found in cow’s milk and found perforated myelin sheaths in those given casein. In MS, the patient’s own immune system destroys that sheath, which leads to paresthesia, vision problems, and movement disorders.
“The body’s defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin, “ said Rittika Chunder, a postdoctoral fellow at the University of Bonn. How? Apparently it’s all a big misunderstanding.
While looking at molecules needed for myelin production, the researchers came across MAG, which is very similar to casein, which is a problem when patients with MS are allergic to casein. After they have dairy products, the B-cell squad gets called in to clean up the evil twin, casein, but can’t differentiate it from the good twin, MAG, so it all gets a wash and the myelin sheath suffers.
Since this happens only to patients with MS who have a casein allergy, the researchers advise them to stay away from milk, yogurt, or cottage cheese while they work on a self-test to check if patients carry the antibodies.
A small price to pay, perhaps, to stop a villainous evil twin.
You would even say it glows
If you’re anything like us – and we think you are since you’re reading this – you’ve been asking yourself: Are there any common medications in my house that will make good radiation sensors?
Not that anyone needs to worry about excess radiation or anything. Far from it. We were just wondering.
It just so happens that Anna Mrozik and Paweł Bilski, both of the Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) in Kraków, Poland, were wondering the same thing: “During an uncontrolled release of radiation, it is highly unlikely that members of the public will be equipped with personal radiation dose monitors.”
People would need to use something they had lying around the house. A smartphone would work, the investigators explained in a statement from the IFJ PAN, but the process of converting one to radiation-sensor duty, which involves dismantling it and breaking the display glass, “is laborious and time-consuming [and] the destruction of a valuable and useful device does not seem to be the optimal solution.”
Naturally, they turned to drugs. The key, in this case, is optically stimulated luminescence. They needed to find materials that would glow with greater intensity as the radiation dose increased. Turns out that ibuprofen- and paracetamol-based painkillers fit the bill quite nicely, although aspirin also works.
It’s not known exactly which substance is causing the luminescence, but rest assured, the “physicists from the IFJ PAN intend to identify it.”
This is why you don’t interrupt someone using headphones
There’s nothing like taking a nice relaxing walk with your headphones. Whether you’re listening to a podcast or a song or talking on the phone, it’s an escape from reality that makes you feel like you’re completely in tune with what you’re listening to.
According to a new study, headphones, as opposed to speakers, make people feel more connected to what they are listening to. Data collected from more than 4,000 people showed that listening with headphones makes more of an impact than listening to speakers.
“Headphones produce a phenomenon called in-head localization, which makes the speaker sound as if they’re inside your head,” study coauthor On Amir of the University of California, San Diego, said in a statement. Because of this, people feel like the speakers are close to them and there’s more of a sense of empathy for the speakers and the listener is more likely to be swayed toward the ideas of the speaker.
These findings could lead to more efficient training programs, online work, and advertising, the investigators suggested.
We now finally understand why people get so mad when they have to take out their headphones to answer or talk to us. We ruined a satisfying moment going on in their brains.
Chocolate: Now part of a well-balanced diet
Asking if someone loves chocolate is like asking if they love breathing. It’s really not a question that needs to be asked. The thing with chocolate, however, is that most people who love chocolate actually love sugar, since your typical milk chocolate contains only about 30% cacao. The rest, of course, is sugar.
Now, dark chocolate is actually kind of good for you since it contains beneficial flavonoids and less sugar. But that healthiness comes at a cost: Dark chocolate is quite bitter, and gets more so as the cacao content rises, to the point where 100% cacao chocolate is very nearly inedible. That’s the chocolate conundrum, the healthier it is, the worse it tastes. But what if there’s another way? What if you can have tasty chocolate that’s good for you?
That’s the question a group of researchers from Penn State University dared to ask. The secret, they discovered, is to subject the cacao beans to extra-intense roasting. We’re not sure how screaming insults at a bunch of beans will help, but if science says so ... YOU USELESS LUMP OF BARELY EDIBLE FOOD! HOW DARE YOU EXIST!
Oh, not that kind of roasting. Oops.
For their study, the researchers made 27 unsweetened chocolates, prepared using various cacao bean roasting times and temperatures, and served them to volunteers. Those volunteers reported that chocolates made with cacao beans roasted more intensely (such as 20 minutes at 340° F, 80 min at 275° F, and 54 min at 304° F) were far more acceptable than were chocolates prepared with raw or lightly roasted cacao beans.
The implications of healthy yet tasty chocolate are obvious: Master the chocolate and you’ll make millions. Imagine a future where parents say to their kids: “Don’t forget to eat your chocolate.” So, we’re off to do some cooking. Don’t want Hershey to make all the money off of this revelation.
The villain hiding in dairy for some MS patients
For some of us, lactose can be a real heartbreaker when it comes to dairy consumption, but for people with multiple sclerosis (MS) there’s another villain they may also have to face that can make their symptoms worse.
Physicians at the Institute of Anatomy at University Hospital Bonn (Germany) were getting so many complaints from patients with MS about how much worse they felt about after having cheese, yogurt, and milk that they decided to get to the bottom of it. The culprit, it seems, is casein, a protein specifically found in cow’s milk.
The researchers injected mice with various proteins found in cow’s milk and found perforated myelin sheaths in those given casein. In MS, the patient’s own immune system destroys that sheath, which leads to paresthesia, vision problems, and movement disorders.
“The body’s defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin, “ said Rittika Chunder, a postdoctoral fellow at the University of Bonn. How? Apparently it’s all a big misunderstanding.
While looking at molecules needed for myelin production, the researchers came across MAG, which is very similar to casein, which is a problem when patients with MS are allergic to casein. After they have dairy products, the B-cell squad gets called in to clean up the evil twin, casein, but can’t differentiate it from the good twin, MAG, so it all gets a wash and the myelin sheath suffers.
Since this happens only to patients with MS who have a casein allergy, the researchers advise them to stay away from milk, yogurt, or cottage cheese while they work on a self-test to check if patients carry the antibodies.
A small price to pay, perhaps, to stop a villainous evil twin.
You would even say it glows
If you’re anything like us – and we think you are since you’re reading this – you’ve been asking yourself: Are there any common medications in my house that will make good radiation sensors?
Not that anyone needs to worry about excess radiation or anything. Far from it. We were just wondering.
It just so happens that Anna Mrozik and Paweł Bilski, both of the Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) in Kraków, Poland, were wondering the same thing: “During an uncontrolled release of radiation, it is highly unlikely that members of the public will be equipped with personal radiation dose monitors.”
People would need to use something they had lying around the house. A smartphone would work, the investigators explained in a statement from the IFJ PAN, but the process of converting one to radiation-sensor duty, which involves dismantling it and breaking the display glass, “is laborious and time-consuming [and] the destruction of a valuable and useful device does not seem to be the optimal solution.”
Naturally, they turned to drugs. The key, in this case, is optically stimulated luminescence. They needed to find materials that would glow with greater intensity as the radiation dose increased. Turns out that ibuprofen- and paracetamol-based painkillers fit the bill quite nicely, although aspirin also works.
It’s not known exactly which substance is causing the luminescence, but rest assured, the “physicists from the IFJ PAN intend to identify it.”
This is why you don’t interrupt someone using headphones
There’s nothing like taking a nice relaxing walk with your headphones. Whether you’re listening to a podcast or a song or talking on the phone, it’s an escape from reality that makes you feel like you’re completely in tune with what you’re listening to.
According to a new study, headphones, as opposed to speakers, make people feel more connected to what they are listening to. Data collected from more than 4,000 people showed that listening with headphones makes more of an impact than listening to speakers.
“Headphones produce a phenomenon called in-head localization, which makes the speaker sound as if they’re inside your head,” study coauthor On Amir of the University of California, San Diego, said in a statement. Because of this, people feel like the speakers are close to them and there’s more of a sense of empathy for the speakers and the listener is more likely to be swayed toward the ideas of the speaker.
These findings could lead to more efficient training programs, online work, and advertising, the investigators suggested.
We now finally understand why people get so mad when they have to take out their headphones to answer or talk to us. We ruined a satisfying moment going on in their brains.
Evidence mounts for paramagnetic rim lesions in diagnosing MS
WEST PALM BEACH, FLA. – , new research suggests.
Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.
Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.
“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.
The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
Sign of aggressive disease?
Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.
In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.
At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).
At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.
Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.
The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).
After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).
Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).
“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.
“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.
Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
Diagnostic value
The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).
Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.
Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.
Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.
“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
Promising data
During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.
“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.
“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.
Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”
Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”
Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.
“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.
During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.
Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research suggests.
Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.
Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.
“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.
The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
Sign of aggressive disease?
Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.
In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.
At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).
At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.
Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.
The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).
After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).
Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).
“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.
“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.
Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
Diagnostic value
The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).
Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.
Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.
Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.
“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
Promising data
During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.
“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.
“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.
Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”
Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”
Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.
“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.
During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.
Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research suggests.
Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.
Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.
“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.
The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
Sign of aggressive disease?
Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.
In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.
At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).
At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.
Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.
The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).
After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).
Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).
“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.
“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.
Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
Diagnostic value
The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).
Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.
Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.
Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.
“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
Promising data
During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.
“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.
“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.
Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”
Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”
Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.
“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.
During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.
Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
REPORTING FROM ACTRIMS FORUM 2022
Spinal cord atrophy predicts ‘silent progression’ in MS
WEST PALM BEACH, FLA. – , new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.
“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.
“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.
Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Relatively new concept
Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.
However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.
“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).
To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.
They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.
To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.
Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
‘Strongest predictor’
The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).
Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).
“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.
Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.
Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).
“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
Standard of care?
While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.
Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.
“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
Treatment implications
Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.
“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.
Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.
“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.
Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.
He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.
“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.
Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.
“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.
“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.
Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Relatively new concept
Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.
However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.
“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).
To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.
They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.
To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.
Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
‘Strongest predictor’
The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).
Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).
“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.
Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.
Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).
“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
Standard of care?
While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.
Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.
“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
Treatment implications
Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.
“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.
Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.
“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.
Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.
He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.
“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.
Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.
“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.
“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.
Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Relatively new concept
Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.
However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.
“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).
To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.
They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.
To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.
Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
‘Strongest predictor’
The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).
Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).
“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.
Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.
Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).
“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
Standard of care?
While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.
Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.
“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
Treatment implications
Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.
“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.
Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.
“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.
Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.
He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.
“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.
Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.
A version of this article first appeared on Medscape.com.
REPORTING FROM ACTRIMS FORUM 2022
Clinical Edge Journal Scan Commentary: Multiple Sclerosis March 2022
Web-based mindfulness program improves depressive symptoms in MS
Key clinical point: Patients with multiple sclerosis (pwMS) who participated in a web-based mindfulness-based intervention (MBI) showed significant improvements in depressive symptoms and health-related quality of life (HRQoL).
Major finding: The MBI group showed a significant improvement in depressive symptoms compared with the waitlist (Cohen’s d 0.39; 95% CI, 0.034-0.742), with patients with recurrent depressive symptoms benefitting the most (P = .034). MBI had a positive effect on HRQoL regardless of previous depressive history (P = .009).
Study details: The findings come from a randomized controlled trial involving 132 pwMS with or without a history of recurrent depression, and who received either an internet-delivered MBI (n = 69) or were assigned to a waitlist (n = 63).
Disclosures: This study was supported by the National Health and Medical Research Council and Multiple Sclerosis Research, Australia. The authors declared no conflict of interests.
Source: Sesel AL et al. Mult Scler. 2022 (Feb 7). Doi: 10.1177/13524585211068002.
Key clinical point: Patients with multiple sclerosis (pwMS) who participated in a web-based mindfulness-based intervention (MBI) showed significant improvements in depressive symptoms and health-related quality of life (HRQoL).
Major finding: The MBI group showed a significant improvement in depressive symptoms compared with the waitlist (Cohen’s d 0.39; 95% CI, 0.034-0.742), with patients with recurrent depressive symptoms benefitting the most (P = .034). MBI had a positive effect on HRQoL regardless of previous depressive history (P = .009).
Study details: The findings come from a randomized controlled trial involving 132 pwMS with or without a history of recurrent depression, and who received either an internet-delivered MBI (n = 69) or were assigned to a waitlist (n = 63).
Disclosures: This study was supported by the National Health and Medical Research Council and Multiple Sclerosis Research, Australia. The authors declared no conflict of interests.
Source: Sesel AL et al. Mult Scler. 2022 (Feb 7). Doi: 10.1177/13524585211068002.
Key clinical point: Patients with multiple sclerosis (pwMS) who participated in a web-based mindfulness-based intervention (MBI) showed significant improvements in depressive symptoms and health-related quality of life (HRQoL).
Major finding: The MBI group showed a significant improvement in depressive symptoms compared with the waitlist (Cohen’s d 0.39; 95% CI, 0.034-0.742), with patients with recurrent depressive symptoms benefitting the most (P = .034). MBI had a positive effect on HRQoL regardless of previous depressive history (P = .009).
Study details: The findings come from a randomized controlled trial involving 132 pwMS with or without a history of recurrent depression, and who received either an internet-delivered MBI (n = 69) or were assigned to a waitlist (n = 63).
Disclosures: This study was supported by the National Health and Medical Research Council and Multiple Sclerosis Research, Australia. The authors declared no conflict of interests.
Source: Sesel AL et al. Mult Scler. 2022 (Feb 7). Doi: 10.1177/13524585211068002.
Early decline in lymphocyte count best predicts DMF-associated lymphopenia in relapsing MS
Key clinical point: A significant reduction in absolute lymphocyte counts (ALC) early after the initiation of dimethyl fumarate (DMF) was strongly associated with the development of severe lymphopenia in patients with relapsing multiple sclerosis (MS).
Major finding: A decline in mean ALC of ≥21.2% within the first 3 months of treatment increased the risk for DMF associated-lymphopenia by 6.5-fold (adjusted hazard risk [aHR] 6.503), whereas a decline of ≥40.2% increased the risk for severe lymphopenia by 12.67-fold (aHR 12.67; both P < .001).
Study details: The findings come from a multicenter, noninterventional, prospective real-world study involving 532 patients with relapsing MS who initiated taking DMF.
Disclosures: No funding was received for conducting this study. The authors, including the lead author, declared serving on the advisory board or receiving research/travel grants and speaker/consultancy fees from various sources.
Source: Sainz de la Maza S et al. Mult Scler Relat Disor. 2022;59:103669 (Feb 4). Doi: 10.1016/j.msard.2022.103669.
Key clinical point: A significant reduction in absolute lymphocyte counts (ALC) early after the initiation of dimethyl fumarate (DMF) was strongly associated with the development of severe lymphopenia in patients with relapsing multiple sclerosis (MS).
Major finding: A decline in mean ALC of ≥21.2% within the first 3 months of treatment increased the risk for DMF associated-lymphopenia by 6.5-fold (adjusted hazard risk [aHR] 6.503), whereas a decline of ≥40.2% increased the risk for severe lymphopenia by 12.67-fold (aHR 12.67; both P < .001).
Study details: The findings come from a multicenter, noninterventional, prospective real-world study involving 532 patients with relapsing MS who initiated taking DMF.
Disclosures: No funding was received for conducting this study. The authors, including the lead author, declared serving on the advisory board or receiving research/travel grants and speaker/consultancy fees from various sources.
Source: Sainz de la Maza S et al. Mult Scler Relat Disor. 2022;59:103669 (Feb 4). Doi: 10.1016/j.msard.2022.103669.
Key clinical point: A significant reduction in absolute lymphocyte counts (ALC) early after the initiation of dimethyl fumarate (DMF) was strongly associated with the development of severe lymphopenia in patients with relapsing multiple sclerosis (MS).
Major finding: A decline in mean ALC of ≥21.2% within the first 3 months of treatment increased the risk for DMF associated-lymphopenia by 6.5-fold (adjusted hazard risk [aHR] 6.503), whereas a decline of ≥40.2% increased the risk for severe lymphopenia by 12.67-fold (aHR 12.67; both P < .001).
Study details: The findings come from a multicenter, noninterventional, prospective real-world study involving 532 patients with relapsing MS who initiated taking DMF.
Disclosures: No funding was received for conducting this study. The authors, including the lead author, declared serving on the advisory board or receiving research/travel grants and speaker/consultancy fees from various sources.
Source: Sainz de la Maza S et al. Mult Scler Relat Disor. 2022;59:103669 (Feb 4). Doi: 10.1016/j.msard.2022.103669.
Primary progressive MS: No difference in efficacy between rituximab and ocrelizumab in real world
Key clinical point: The time to confirmed disability progression (CDP) and serum neurofilament light chain levels (sNfL) was not significantly different in patients with primary progressive multiple sclerosis (pwPPMS), who received treatment with rituximab or ocrelizumab.
Major finding: After a mean follow-up of 18.3 months, rituximab vs. ocrelizumab groups showed no significant difference in the proportion of patients with CDP (30.6% vs. 23.9%; P = .356). The mean sNfL level was not significantly different between the groups (P = .192).
Study details: The findings come from a multicentric observational study involving 111 pwPPMS who started treatment with ocrelizumab or rituximab.
Disclosures: This study was supported by the Health Institute Carlos III and FEDER funding. Four authors reported receiving travel grants and consulting/speaker fees from various sources.
Source: Alcalá C et al. J Neurol. 2022 (Feb 2). Doi: 10.1007/s00415-022-10989-0
Key clinical point: The time to confirmed disability progression (CDP) and serum neurofilament light chain levels (sNfL) was not significantly different in patients with primary progressive multiple sclerosis (pwPPMS), who received treatment with rituximab or ocrelizumab.
Major finding: After a mean follow-up of 18.3 months, rituximab vs. ocrelizumab groups showed no significant difference in the proportion of patients with CDP (30.6% vs. 23.9%; P = .356). The mean sNfL level was not significantly different between the groups (P = .192).
Study details: The findings come from a multicentric observational study involving 111 pwPPMS who started treatment with ocrelizumab or rituximab.
Disclosures: This study was supported by the Health Institute Carlos III and FEDER funding. Four authors reported receiving travel grants and consulting/speaker fees from various sources.
Source: Alcalá C et al. J Neurol. 2022 (Feb 2). Doi: 10.1007/s00415-022-10989-0
Key clinical point: The time to confirmed disability progression (CDP) and serum neurofilament light chain levels (sNfL) was not significantly different in patients with primary progressive multiple sclerosis (pwPPMS), who received treatment with rituximab or ocrelizumab.
Major finding: After a mean follow-up of 18.3 months, rituximab vs. ocrelizumab groups showed no significant difference in the proportion of patients with CDP (30.6% vs. 23.9%; P = .356). The mean sNfL level was not significantly different between the groups (P = .192).
Study details: The findings come from a multicentric observational study involving 111 pwPPMS who started treatment with ocrelizumab or rituximab.
Disclosures: This study was supported by the Health Institute Carlos III and FEDER funding. Four authors reported receiving travel grants and consulting/speaker fees from various sources.
Source: Alcalá C et al. J Neurol. 2022 (Feb 2). Doi: 10.1007/s00415-022-10989-0
sNfL and disease course in progressive MS without acute inflammation: Is there a link?
Key clinical point: Changes in serum neurofilament light chain (sNfL) may not be a dynamic biomarker related to confirmed disability progression (CDP) in patients with secondary progressive multiple sclerosis (SPMS) without acute inflammation.
Major finding: At 48 weeks, changes in sNfL were not associated with the risk for CDP in the natalizumab (odds ratio [OR] per 10% increase in sNfL 1.02; 95% CI 0.86-1.21) and placebo (OR per 10% increase in sNfL 0.90; 95% CI 0.64-1.27) groups.
Study details: The findings come from a post hoc analysis of the ASCEND trial involving 317 patients with SPMS without acute inflammation who were randomly assigned to receive either natalizumab (n = 214) or placebo (n = 103).
Disclosures: This study was supported by Biogen. Dr. Zetterberg and Dr. Fox reported receiving personal fees or research contracts from various sources including Biogen. Dr. Belachew reported being an employee and shareholder of Biogen.
Source: Gafson AR et al. JAMA Netw Open. 2022;5(2):e2147588 (Feb 8). Doi: 10.1001/jamanetworkopen.2021.47588
Key clinical point: Changes in serum neurofilament light chain (sNfL) may not be a dynamic biomarker related to confirmed disability progression (CDP) in patients with secondary progressive multiple sclerosis (SPMS) without acute inflammation.
Major finding: At 48 weeks, changes in sNfL were not associated with the risk for CDP in the natalizumab (odds ratio [OR] per 10% increase in sNfL 1.02; 95% CI 0.86-1.21) and placebo (OR per 10% increase in sNfL 0.90; 95% CI 0.64-1.27) groups.
Study details: The findings come from a post hoc analysis of the ASCEND trial involving 317 patients with SPMS without acute inflammation who were randomly assigned to receive either natalizumab (n = 214) or placebo (n = 103).
Disclosures: This study was supported by Biogen. Dr. Zetterberg and Dr. Fox reported receiving personal fees or research contracts from various sources including Biogen. Dr. Belachew reported being an employee and shareholder of Biogen.
Source: Gafson AR et al. JAMA Netw Open. 2022;5(2):e2147588 (Feb 8). Doi: 10.1001/jamanetworkopen.2021.47588
Key clinical point: Changes in serum neurofilament light chain (sNfL) may not be a dynamic biomarker related to confirmed disability progression (CDP) in patients with secondary progressive multiple sclerosis (SPMS) without acute inflammation.
Major finding: At 48 weeks, changes in sNfL were not associated with the risk for CDP in the natalizumab (odds ratio [OR] per 10% increase in sNfL 1.02; 95% CI 0.86-1.21) and placebo (OR per 10% increase in sNfL 0.90; 95% CI 0.64-1.27) groups.
Study details: The findings come from a post hoc analysis of the ASCEND trial involving 317 patients with SPMS without acute inflammation who were randomly assigned to receive either natalizumab (n = 214) or placebo (n = 103).
Disclosures: This study was supported by Biogen. Dr. Zetterberg and Dr. Fox reported receiving personal fees or research contracts from various sources including Biogen. Dr. Belachew reported being an employee and shareholder of Biogen.
Source: Gafson AR et al. JAMA Netw Open. 2022;5(2):e2147588 (Feb 8). Doi: 10.1001/jamanetworkopen.2021.47588
High or increasing sNfl level predictive of impending relapses in active multiple sclerosis
Key clinical point: Both elevated levels of baseline serum neurofilament light chain (sNfL) and increasing levels from a low baseline were associated with multiple sclerosis (MS) relapses, indicating the utility of sNfL in identifying patients who may benefit from early treatment optimization.
Major finding: A 2-fold increase in baseline sNfL was associated with a 1.9-fold increased risk for relapse during follow-up (adjusted hazard ratio [aHR] 1.90; P < .01) and a 2-fold longitudinal increase in sNfL from its first measurement increased the risk for relapse by 1.41-fold (aHR 1.41; P = .04).
Study details: Findings are from an analysis of 58 patients with active MS who were prospectively followed for 1 year as a part of clinical trial.
Disclosures: This study received funding from the MS Society of Canada, Fondazione Italiana Sclerosi Multipla, and Research Manitoba. The authors reported no conflict of interests.
Source: Thebault S et al. Mult Scler Relat Disord. 2022;59:103535 (Jan 18). Doi: 10.1016/j.msard.2022.103535
Key clinical point: Both elevated levels of baseline serum neurofilament light chain (sNfL) and increasing levels from a low baseline were associated with multiple sclerosis (MS) relapses, indicating the utility of sNfL in identifying patients who may benefit from early treatment optimization.
Major finding: A 2-fold increase in baseline sNfL was associated with a 1.9-fold increased risk for relapse during follow-up (adjusted hazard ratio [aHR] 1.90; P < .01) and a 2-fold longitudinal increase in sNfL from its first measurement increased the risk for relapse by 1.41-fold (aHR 1.41; P = .04).
Study details: Findings are from an analysis of 58 patients with active MS who were prospectively followed for 1 year as a part of clinical trial.
Disclosures: This study received funding from the MS Society of Canada, Fondazione Italiana Sclerosi Multipla, and Research Manitoba. The authors reported no conflict of interests.
Source: Thebault S et al. Mult Scler Relat Disord. 2022;59:103535 (Jan 18). Doi: 10.1016/j.msard.2022.103535
Key clinical point: Both elevated levels of baseline serum neurofilament light chain (sNfL) and increasing levels from a low baseline were associated with multiple sclerosis (MS) relapses, indicating the utility of sNfL in identifying patients who may benefit from early treatment optimization.
Major finding: A 2-fold increase in baseline sNfL was associated with a 1.9-fold increased risk for relapse during follow-up (adjusted hazard ratio [aHR] 1.90; P < .01) and a 2-fold longitudinal increase in sNfL from its first measurement increased the risk for relapse by 1.41-fold (aHR 1.41; P = .04).
Study details: Findings are from an analysis of 58 patients with active MS who were prospectively followed for 1 year as a part of clinical trial.
Disclosures: This study received funding from the MS Society of Canada, Fondazione Italiana Sclerosi Multipla, and Research Manitoba. The authors reported no conflict of interests.
Source: Thebault S et al. Mult Scler Relat Disord. 2022;59:103535 (Jan 18). Doi: 10.1016/j.msard.2022.103535
Multiple sclerosis: Excellent response to SARS-CoV-2 vaccine in patients with MS
Key clinical point: Patients with multiple sclerosis (MS) who were untreated or received immunomodulatory disease-modifying treatments (IM-DMT) showed excellent seroconversion rates after SARS-CoV-2 vaccination; however, immunosuppressive DMT (IS-DMT) was associated with lower seroconversion rates.
Major finding: For these patients 3 months after vaccine dose seroconversion occurred in 96.7% of untreated, 97.1% of IM-DMT treated, and 61.1% of IS-DMT treated patients vs. 97.4% of healthy control individuals (P < .001), with IS-DMT being the only significant predictor of seroconversion (odds ratio 0.04; P < .001).
Study details: The finding comes from a multicenter, prospective study involving 456 patients with MS who were either untreated (n = 91) or treated with DMT (IM-DMT, n = 139; IS-DMT, n = 226) and 116 healthy control individuals, all of whom were willing to be vaccinated against SARS-CoV-2.
Disclosures: This study was supported by the Austrian Multiple Sclerosis Society and others. Some of the authors declared serving as an advisor or receiving speaker honoraria, scientific grants, travel funding, and consulting from various sources.
Source: Bsteh G et al. Eur J Neurol. 2022 (Feb 1). Doi: 10.1111/ene.15265
Key clinical point: Patients with multiple sclerosis (MS) who were untreated or received immunomodulatory disease-modifying treatments (IM-DMT) showed excellent seroconversion rates after SARS-CoV-2 vaccination; however, immunosuppressive DMT (IS-DMT) was associated with lower seroconversion rates.
Major finding: For these patients 3 months after vaccine dose seroconversion occurred in 96.7% of untreated, 97.1% of IM-DMT treated, and 61.1% of IS-DMT treated patients vs. 97.4% of healthy control individuals (P < .001), with IS-DMT being the only significant predictor of seroconversion (odds ratio 0.04; P < .001).
Study details: The finding comes from a multicenter, prospective study involving 456 patients with MS who were either untreated (n = 91) or treated with DMT (IM-DMT, n = 139; IS-DMT, n = 226) and 116 healthy control individuals, all of whom were willing to be vaccinated against SARS-CoV-2.
Disclosures: This study was supported by the Austrian Multiple Sclerosis Society and others. Some of the authors declared serving as an advisor or receiving speaker honoraria, scientific grants, travel funding, and consulting from various sources.
Source: Bsteh G et al. Eur J Neurol. 2022 (Feb 1). Doi: 10.1111/ene.15265
Key clinical point: Patients with multiple sclerosis (MS) who were untreated or received immunomodulatory disease-modifying treatments (IM-DMT) showed excellent seroconversion rates after SARS-CoV-2 vaccination; however, immunosuppressive DMT (IS-DMT) was associated with lower seroconversion rates.
Major finding: For these patients 3 months after vaccine dose seroconversion occurred in 96.7% of untreated, 97.1% of IM-DMT treated, and 61.1% of IS-DMT treated patients vs. 97.4% of healthy control individuals (P < .001), with IS-DMT being the only significant predictor of seroconversion (odds ratio 0.04; P < .001).
Study details: The finding comes from a multicenter, prospective study involving 456 patients with MS who were either untreated (n = 91) or treated with DMT (IM-DMT, n = 139; IS-DMT, n = 226) and 116 healthy control individuals, all of whom were willing to be vaccinated against SARS-CoV-2.
Disclosures: This study was supported by the Austrian Multiple Sclerosis Society and others. Some of the authors declared serving as an advisor or receiving speaker honoraria, scientific grants, travel funding, and consulting from various sources.
Source: Bsteh G et al. Eur J Neurol. 2022 (Feb 1). Doi: 10.1111/ene.15265