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High-dose vitamin D and MS relapse: New phase 3 data
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
FROM ECLINICALMEDICINE
Machine learning can predict primary progressive MS progression
BOSTON – , according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.
The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.
“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.
In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
Machine learning analyzes blood samples
The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.
In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.
After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).
The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).
The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.
On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.
On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively
Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.
If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
A useful tool
In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.
For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.
Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.
In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.
“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.
Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.
BOSTON – , according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.
The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.
“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.
In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
Machine learning analyzes blood samples
The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.
In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.
After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).
The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).
The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.
On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.
On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively
Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.
If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
A useful tool
In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.
For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.
Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.
In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.
“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.
Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.
BOSTON – , according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.
The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.
“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.
In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
Machine learning analyzes blood samples
The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.
In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.
After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).
The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).
The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.
On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.
On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively
Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.
If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
A useful tool
In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.
For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.
Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.
In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.
“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.
Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.
FROM AAN 2023
Raising Awareness for Managing Disease-Modifying Therapies in Aging Persons With Multiple Sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years.
Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.
Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer.
The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision.
The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.
The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.
DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:
Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.
Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues.
Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.
Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years.
Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.
Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer.
The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision.
The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.
The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.
DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:
Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.
Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues.
Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.
Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years.
Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.
Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer.
The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision.
The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.
The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.
DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:
Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.
Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues.
Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.
Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.
Mediterranean diet improves cognition in MS
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
FROM AAN 2023
Risk for MS in children often missed
Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.
The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.
“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.
Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.
Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.
While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.
The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.
Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.
MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.
“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”
The findings were published in the journal Multiple Sclerosis and Related Disorders.
According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.
“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”
MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.
“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”
Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.
“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”
For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.
“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”
Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.
A version of this article originally appeared on Medscape.com.
Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.
The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.
“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.
Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.
Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.
While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.
The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.
Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.
MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.
“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”
The findings were published in the journal Multiple Sclerosis and Related Disorders.
According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.
“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”
MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.
“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”
Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.
“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”
For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.
“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”
Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.
A version of this article originally appeared on Medscape.com.
Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.
The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.
“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.
Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.
Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.
While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.
The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.
Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.
MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.
“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”
The findings were published in the journal Multiple Sclerosis and Related Disorders.
According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.
“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”
MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.
“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”
Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.
“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”
For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.
“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”
Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.
A version of this article originally appeared on Medscape.com.
Can particles in dairy and beef cause cancer and MS?
In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?
However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.
In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.
Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
Acid radicals
However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.
According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
Viral progeny
In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.
The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
‘Breast milk is healthy’
Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.
The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
Colon cancer
To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.
The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
Institutional skepticism
When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?
The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.
BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.
Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
Association with MS?
Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”
However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.
Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?
However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.
In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.
Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
Acid radicals
However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.
According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
Viral progeny
In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.
The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
‘Breast milk is healthy’
Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.
The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
Colon cancer
To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.
The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
Institutional skepticism
When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?
The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.
BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.
Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
Association with MS?
Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”
However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.
Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?
However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.
In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.
Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
Acid radicals
However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.
According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
Viral progeny
In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.
The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
‘Breast milk is healthy’
Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.
The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
Colon cancer
To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.
The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
Institutional skepticism
When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?
The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.
BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.
Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
Association with MS?
Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”
However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.
Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
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.
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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