ICYMI: MSVirtual2020 Virtual Joint ACTRIMS-ECTRIMS Meeting Summary from MS Resource Center Editor in Chief, Joseph R. Berger, MD

I had the privilege of attending and speaking at the recent MSVirtual2020—the 8^th Joint ACTRIMS-ECTRIMS Meeting. I came away with a wealth of knowledge, much of which can be put to immediate use in practice, and some that shows the promise of eventual clinical utility.

Dr. Helen Tremlett, PhD, kicked off the meeting with a keynote address covering her important work on the MS prodrome.  The Canada research chair in neuroepidemiology and multiple sclerosis at the University of British Columbia summarized her team’s research to date and offered her thoughts on clinical implications.

Dr. Tremlett’s group has observed that in the five years before an MS symptom onset, individuals who would ultimately be diagnosed tended to experience more hospitalizations, visit their provider more, and fill more prescriptions than did those in the general population. The team dug deeper and found that these individuals experienced a range of issues prior to symptom onset, including pain, headache, migraine, fibromyalgia, irritable bowel syndrome, sleep disturbances, depression/anxiety, and dermatologic issues.

Interestingly, females in this group were less likely to become pregnant and more likely than healthy females to fill an oral contraceptive prescription, suggesting that they were trying to delay pregnancy due to these prodromal symptoms.

Dr. Tremlett noted that the more immediate implications of her group’s work are for clinical researchers, who can now use these findings to understand that there is a prodromal stage as they conduct clinical trials. The ultimate aim is to use this work to develop a diagnostic tool, but that will take more time and study.

COVID-19’s Impact on MS

The impact on COVID-19 on individuals with MS was addressed in a number of sessions. I presented data that clearly shows the risk of infection from COVID-19 is similar to that of the population at large.

• A critical evaluation of MS disease modifying therapies (DMTs) and their potential effects on COVID-19 that I published with my colleagues at the University of Pennsylvania suggested that DMTs might not increase the risk of morbidity and mortality associated with COVID-19 as some had feared. We based this conclusion on an evaluation of pathogenesis of COVID, the importance of the innate immune system in control of exposure to a novel pathogen, and the likely effects, both salutary and pernicious, of DMTs on COVID morbidity and mortality.
•  Investigators from Italy looked at 232 patients from 38 centers with MS and confirmed or suspected COVID and found that the vast majority of them (96%) had mild disease consisting of no or mild pneumonia. The remainder had either severe (2%) or critical (3%) disease.  These investigators have since expanded their observations and suggested that anti-CD20 monoclonal antibody treatment may be associated with a higher risk of hospitalization, though there did not appear to be an increase in the risk of death with their use.  Importantly, the anti-CD20 monoclonal antibody therapies are the DMTs routinely used in patients with progressive MS, generally, the MS population at greatest risk of hospitalization with COVID-19 due to their older age, co-morbidities, and level of debility.
• Recently, French researchers evaluated 347 individuals with MS and COVID by COVID disease severity. They found that there was a higher proportion of patients with severe COVID not receiving DMT compared with individuals receiving treatment (46% and 15%, respectively).

The Increasing Importance of sNfL Concentration

Serum neurofilament light chain (sNfL) concentration continues to be a hot topic. Dr. Jens Kuhle, head of the Multiple Sclerosis Centre at the University of Basel, and colleagues have demonstrated that sNfL levels can play a role in monitoring MS treatment in practice. They evaluated more than 1000 individuals who were taking DMTs, measuring sNfL and deriving a score that reflected how participants fared relative to healthy controls of the same age. Among their findings:

• The resulting score predicted clinical events in the following year, with the effect escalating in magnitude in those whose scores were higher.
• This same predictive effect was seen with respect to future new/enlarging T2 lesions and brain volume loss.
• Score change in patients with NEDA-03 status was linked with a 37% increased risk of clinical events in the following year.

New Radiologic Techniques

Encouraging findings on new radiologic techniques were presented. I found three studies extremely informative. The first two have immediate or near-immediate clinical implications, and the third shows promise.

• In a comparison of patients with MS and healthy individuals who underwent brain 3T MRI to assess lesions and atrophy, R. Bonacchi and colleagues from Milan, Italy found that cardiovascular (CV) risk factors are linked with brain atrophy in patients with MS, even those <50 years of age. Specifically, the presence of at least two CV risk factors was linked with reduced normalized grey matter volume, white matter volume, and brain volume.
• Another comparison of individuals with MS and healthy controls—this one from O. Al-Louzi and colleagues at the National Institute of Neurological Disorders and Stroke—looked at the central vein sign (CVS) biomarker and determined that excluding lesions only if all dimensions of 3T MRI results were less than threshold (versus if any dimension was less than threshold) led to the inclusion of more CVS-positive lesions. Investigators suggested this work could lead to modified clinical guidelines.
• In an evaluation of patients with MS using 3T MRI, F. LaRosa and colleagues from Lausanne, Switzerland reported that RimNet, a prototype built upon two convolutional neural networks, was better than two alternative methods at detecting pragmatic rim lesions, which are linked with higher disease burden. Compared with expert raters, RimNet had higher sensitivity (87% vs 76%) but lower specificity (91% vs 99%).

There were many other valuable presentations at MSVirtual2020, but perhaps the most appreciated experience was the ability to hear more experts deliver their important work. Unlike a live meeting, I was able to easily attend parallel sessions and to do so at my leisure. ECTRIMS has become so big that I often left the live meeting feeling as if I missed out on a lot. Not this year. I heard almost all of it and came away with a greater appreciation of the breadth and depth of the meeting.  I hope that in the future, even following the return of in-person meetings, a virtual format coexists to afford attendees and those unable to attend live the opportunity to experience the totality of the meeting.

I had the privilege of attending and speaking at the recent MSVirtual2020—the 8^th Joint ACTRIMS-ECTRIMS Meeting. I came away with a wealth of knowledge, much of which can be put to immediate use in practice, and some that shows the promise of eventual clinical utility.

Dr. Helen Tremlett, PhD, kicked off the meeting with a keynote address covering her important work on the MS prodrome.  The Canada research chair in neuroepidemiology and multiple sclerosis at the University of British Columbia summarized her team’s research to date and offered her thoughts on clinical implications.

Dr. Tremlett’s group has observed that in the five years before an MS symptom onset, individuals who would ultimately be diagnosed tended to experience more hospitalizations, visit their provider more, and fill more prescriptions than did those in the general population. The team dug deeper and found that these individuals experienced a range of issues prior to symptom onset, including pain, headache, migraine, fibromyalgia, irritable bowel syndrome, sleep disturbances, depression/anxiety, and dermatologic issues.

Interestingly, females in this group were less likely to become pregnant and more likely than healthy females to fill an oral contraceptive prescription, suggesting that they were trying to delay pregnancy due to these prodromal symptoms.

Dr. Tremlett noted that the more immediate implications of her group’s work are for clinical researchers, who can now use these findings to understand that there is a prodromal stage as they conduct clinical trials. The ultimate aim is to use this work to develop a diagnostic tool, but that will take more time and study.

COVID-19’s Impact on MS

The impact on COVID-19 on individuals with MS was addressed in a number of sessions. I presented data that clearly shows the risk of infection from COVID-19 is similar to that of the population at large.

• A critical evaluation of MS disease modifying therapies (DMTs) and their potential effects on COVID-19 that I published with my colleagues at the University of Pennsylvania suggested that DMTs might not increase the risk of morbidity and mortality associated with COVID-19 as some had feared. We based this conclusion on an evaluation of pathogenesis of COVID, the importance of the innate immune system in control of exposure to a novel pathogen, and the likely effects, both salutary and pernicious, of DMTs on COVID morbidity and mortality.
•  Investigators from Italy looked at 232 patients from 38 centers with MS and confirmed or suspected COVID and found that the vast majority of them (96%) had mild disease consisting of no or mild pneumonia. The remainder had either severe (2%) or critical (3%) disease.  These investigators have since expanded their observations and suggested that anti-CD20 monoclonal antibody treatment may be associated with a higher risk of hospitalization, though there did not appear to be an increase in the risk of death with their use.  Importantly, the anti-CD20 monoclonal antibody therapies are the DMTs routinely used in patients with progressive MS, generally, the MS population at greatest risk of hospitalization with COVID-19 due to their older age, co-morbidities, and level of debility.
• Recently, French researchers evaluated 347 individuals with MS and COVID by COVID disease severity. They found that there was a higher proportion of patients with severe COVID not receiving DMT compared with individuals receiving treatment (46% and 15%, respectively).

The Increasing Importance of sNfL Concentration

Serum neurofilament light chain (sNfL) concentration continues to be a hot topic. Dr. Jens Kuhle, head of the Multiple Sclerosis Centre at the University of Basel, and colleagues have demonstrated that sNfL levels can play a role in monitoring MS treatment in practice. They evaluated more than 1000 individuals who were taking DMTs, measuring sNfL and deriving a score that reflected how participants fared relative to healthy controls of the same age. Among their findings:

• The resulting score predicted clinical events in the following year, with the effect escalating in magnitude in those whose scores were higher.
• This same predictive effect was seen with respect to future new/enlarging T2 lesions and brain volume loss.
• Score change in patients with NEDA-03 status was linked with a 37% increased risk of clinical events in the following year.

New Radiologic Techniques

Encouraging findings on new radiologic techniques were presented. I found three studies extremely informative. The first two have immediate or near-immediate clinical implications, and the third shows promise.

• In a comparison of patients with MS and healthy individuals who underwent brain 3T MRI to assess lesions and atrophy, R. Bonacchi and colleagues from Milan, Italy found that cardiovascular (CV) risk factors are linked with brain atrophy in patients with MS, even those <50 years of age. Specifically, the presence of at least two CV risk factors was linked with reduced normalized grey matter volume, white matter volume, and brain volume.
• Another comparison of individuals with MS and healthy controls—this one from O. Al-Louzi and colleagues at the National Institute of Neurological Disorders and Stroke—looked at the central vein sign (CVS) biomarker and determined that excluding lesions only if all dimensions of 3T MRI results were less than threshold (versus if any dimension was less than threshold) led to the inclusion of more CVS-positive lesions. Investigators suggested this work could lead to modified clinical guidelines.
• In an evaluation of patients with MS using 3T MRI, F. LaRosa and colleagues from Lausanne, Switzerland reported that RimNet, a prototype built upon two convolutional neural networks, was better than two alternative methods at detecting pragmatic rim lesions, which are linked with higher disease burden. Compared with expert raters, RimNet had higher sensitivity (87% vs 76%) but lower specificity (91% vs 99%).

There were many other valuable presentations at MSVirtual2020, but perhaps the most appreciated experience was the ability to hear more experts deliver their important work. Unlike a live meeting, I was able to easily attend parallel sessions and to do so at my leisure. ECTRIMS has become so big that I often left the live meeting feeling as if I missed out on a lot. Not this year. I heard almost all of it and came away with a greater appreciation of the breadth and depth of the meeting.  I hope that in the future, even following the return of in-person meetings, a virtual format coexists to afford attendees and those unable to attend live the opportunity to experience the totality of the meeting.

I had the privilege of attending and speaking at the recent MSVirtual2020—the 8^th Joint ACTRIMS-ECTRIMS Meeting. I came away with a wealth of knowledge, much of which can be put to immediate use in practice, and some that shows the promise of eventual clinical utility.

Dr. Helen Tremlett, PhD, kicked off the meeting with a keynote address covering her important work on the MS prodrome.  The Canada research chair in neuroepidemiology and multiple sclerosis at the University of British Columbia summarized her team’s research to date and offered her thoughts on clinical implications.

Dr. Tremlett’s group has observed that in the five years before an MS symptom onset, individuals who would ultimately be diagnosed tended to experience more hospitalizations, visit their provider more, and fill more prescriptions than did those in the general population. The team dug deeper and found that these individuals experienced a range of issues prior to symptom onset, including pain, headache, migraine, fibromyalgia, irritable bowel syndrome, sleep disturbances, depression/anxiety, and dermatologic issues.

Interestingly, females in this group were less likely to become pregnant and more likely than healthy females to fill an oral contraceptive prescription, suggesting that they were trying to delay pregnancy due to these prodromal symptoms.

Dr. Tremlett noted that the more immediate implications of her group’s work are for clinical researchers, who can now use these findings to understand that there is a prodromal stage as they conduct clinical trials. The ultimate aim is to use this work to develop a diagnostic tool, but that will take more time and study.

COVID-19’s Impact on MS

The impact on COVID-19 on individuals with MS was addressed in a number of sessions. I presented data that clearly shows the risk of infection from COVID-19 is similar to that of the population at large.

• A critical evaluation of MS disease modifying therapies (DMTs) and their potential effects on COVID-19 that I published with my colleagues at the University of Pennsylvania suggested that DMTs might not increase the risk of morbidity and mortality associated with COVID-19 as some had feared. We based this conclusion on an evaluation of pathogenesis of COVID, the importance of the innate immune system in control of exposure to a novel pathogen, and the likely effects, both salutary and pernicious, of DMTs on COVID morbidity and mortality.
•  Investigators from Italy looked at 232 patients from 38 centers with MS and confirmed or suspected COVID and found that the vast majority of them (96%) had mild disease consisting of no or mild pneumonia. The remainder had either severe (2%) or critical (3%) disease.  These investigators have since expanded their observations and suggested that anti-CD20 monoclonal antibody treatment may be associated with a higher risk of hospitalization, though there did not appear to be an increase in the risk of death with their use.  Importantly, the anti-CD20 monoclonal antibody therapies are the DMTs routinely used in patients with progressive MS, generally, the MS population at greatest risk of hospitalization with COVID-19 due to their older age, co-morbidities, and level of debility.
• Recently, French researchers evaluated 347 individuals with MS and COVID by COVID disease severity. They found that there was a higher proportion of patients with severe COVID not receiving DMT compared with individuals receiving treatment (46% and 15%, respectively).

The Increasing Importance of sNfL Concentration

Serum neurofilament light chain (sNfL) concentration continues to be a hot topic. Dr. Jens Kuhle, head of the Multiple Sclerosis Centre at the University of Basel, and colleagues have demonstrated that sNfL levels can play a role in monitoring MS treatment in practice. They evaluated more than 1000 individuals who were taking DMTs, measuring sNfL and deriving a score that reflected how participants fared relative to healthy controls of the same age. Among their findings:

• The resulting score predicted clinical events in the following year, with the effect escalating in magnitude in those whose scores were higher.
• This same predictive effect was seen with respect to future new/enlarging T2 lesions and brain volume loss.
• Score change in patients with NEDA-03 status was linked with a 37% increased risk of clinical events in the following year.

New Radiologic Techniques

Encouraging findings on new radiologic techniques were presented. I found three studies extremely informative. The first two have immediate or near-immediate clinical implications, and the third shows promise.

• In a comparison of patients with MS and healthy individuals who underwent brain 3T MRI to assess lesions and atrophy, R. Bonacchi and colleagues from Milan, Italy found that cardiovascular (CV) risk factors are linked with brain atrophy in patients with MS, even those <50 years of age. Specifically, the presence of at least two CV risk factors was linked with reduced normalized grey matter volume, white matter volume, and brain volume.
• Another comparison of individuals with MS and healthy controls—this one from O. Al-Louzi and colleagues at the National Institute of Neurological Disorders and Stroke—looked at the central vein sign (CVS) biomarker and determined that excluding lesions only if all dimensions of 3T MRI results were less than threshold (versus if any dimension was less than threshold) led to the inclusion of more CVS-positive lesions. Investigators suggested this work could lead to modified clinical guidelines.
• In an evaluation of patients with MS using 3T MRI, F. LaRosa and colleagues from Lausanne, Switzerland reported that RimNet, a prototype built upon two convolutional neural networks, was better than two alternative methods at detecting pragmatic rim lesions, which are linked with higher disease burden. Compared with expert raters, RimNet had higher sensitivity (87% vs 76%) but lower specificity (91% vs 99%).

There were many other valuable presentations at MSVirtual2020, but perhaps the most appreciated experience was the ability to hear more experts deliver their important work. Unlike a live meeting, I was able to easily attend parallel sessions and to do so at my leisure. ECTRIMS has become so big that I often left the live meeting feeling as if I missed out on a lot. Not this year. I heard almost all of it and came away with a greater appreciation of the breadth and depth of the meeting.  I hope that in the future, even following the return of in-person meetings, a virtual format coexists to afford attendees and those unable to attend live the opportunity to experience the totality of the meeting.