ICYMI Multiple Sclerosis

Key clinical point: The correlation of muscle strength in the lower extremity and trunk with walking performance is stronger in patients with multiple sclerosis (MS) having mild disability than in those having moderate disability.

Major finding: The mild vs. moderate disability group exhibited stronger Pearson correlations of muscle strength to Timed 25-Foot Walk (P less than .001) and 6-minute walk test (P less than .001). For Timed 25-Foot Walk, ankle dorsiflexion (P = .002), knee extension (P = .001), and hip abduction (P = .046) had significantly higher beta coefficients in the mild than moderate disability group.

Study details: A cross-sectional study analyzed data of patients with MS having mild disability (Expanded Disability Status scale [EDSS], 0-3.5; n=36) and moderate disability (EDSS, 4.0-5.5; n=36).

Disclosures: Dr J Kittelson received consulting fees for work on advisory and steering committees for CPC Clinical Research, Bayer Healthcare, Janssen Pharmaceuticals, and Pfizer and for work on data and safety monitoring committees from the Cystic Fibrosis Foundation Therapeutics, Novo Nordisk, Pfizer, Genentech, and BioMarin Pharmaceuticals. Dr MM Mañago, J Callesen, U Dalgas, and M Schenkman declared no conflicts of interest. The study did not receive any external funding.

Citation: Mañago MM et al. Mult Scler Relat Disord. 2020 Mar 13. doi: 10.1016/j.msard.2020.102052

Key clinical point: The correlation of muscle strength in the lower extremity and trunk with walking performance is stronger in patients with multiple sclerosis (MS) having mild disability than in those having moderate disability.

Major finding: The mild vs. moderate disability group exhibited stronger Pearson correlations of muscle strength to Timed 25-Foot Walk (P less than .001) and 6-minute walk test (P less than .001). For Timed 25-Foot Walk, ankle dorsiflexion (P = .002), knee extension (P = .001), and hip abduction (P = .046) had significantly higher beta coefficients in the mild than moderate disability group.

Study details: A cross-sectional study analyzed data of patients with MS having mild disability (Expanded Disability Status scale [EDSS], 0-3.5; n=36) and moderate disability (EDSS, 4.0-5.5; n=36).

Disclosures: Dr J Kittelson received consulting fees for work on advisory and steering committees for CPC Clinical Research, Bayer Healthcare, Janssen Pharmaceuticals, and Pfizer and for work on data and safety monitoring committees from the Cystic Fibrosis Foundation Therapeutics, Novo Nordisk, Pfizer, Genentech, and BioMarin Pharmaceuticals. Dr MM Mañago, J Callesen, U Dalgas, and M Schenkman declared no conflicts of interest. The study did not receive any external funding.

Citation: Mañago MM et al. Mult Scler Relat Disord. 2020 Mar 13. doi: 10.1016/j.msard.2020.102052

Key clinical point: The correlation of muscle strength in the lower extremity and trunk with walking performance is stronger in patients with multiple sclerosis (MS) having mild disability than in those having moderate disability.

Major finding: The mild vs. moderate disability group exhibited stronger Pearson correlations of muscle strength to Timed 25-Foot Walk (P less than .001) and 6-minute walk test (P less than .001). For Timed 25-Foot Walk, ankle dorsiflexion (P = .002), knee extension (P = .001), and hip abduction (P = .046) had significantly higher beta coefficients in the mild than moderate disability group.

Study details: A cross-sectional study analyzed data of patients with MS having mild disability (Expanded Disability Status scale [EDSS], 0-3.5; n=36) and moderate disability (EDSS, 4.0-5.5; n=36).

Disclosures: Dr J Kittelson received consulting fees for work on advisory and steering committees for CPC Clinical Research, Bayer Healthcare, Janssen Pharmaceuticals, and Pfizer and for work on data and safety monitoring committees from the Cystic Fibrosis Foundation Therapeutics, Novo Nordisk, Pfizer, Genentech, and BioMarin Pharmaceuticals. Dr MM Mañago, J Callesen, U Dalgas, and M Schenkman declared no conflicts of interest. The study did not receive any external funding.

Citation: Mañago MM et al. Mult Scler Relat Disord. 2020 Mar 13. doi: 10.1016/j.msard.2020.102052

Proposed updates to guidelines for magnetic resonance imaging in patients with multiple sclerosis (MS) are in the works to make the Consortium of Multiple Sclerosis Centers protocol and other international guidelines more similar, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.

“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.

The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
 

Standardizing scans

While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.

David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”

Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.

Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
 

Repositioning consistency is key

Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.

Central vein sign

Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.

“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”

Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
 

PML Surveillance

The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”

International protocol

Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.

Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”

In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.

However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”

“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”

The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.

Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Proposed updates to guidelines for magnetic resonance imaging in patients with multiple sclerosis (MS) are in the works to make the Consortium of Multiple Sclerosis Centers protocol and other international guidelines more similar, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.

“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.

The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
 

Standardizing scans

While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.

David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”

Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.

Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
 

Repositioning consistency is key

Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.

Central vein sign

Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.

“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”

Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
 

PML Surveillance

The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”

International protocol

Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.

Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”

In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.

However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”

“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”

The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.

Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Proposed updates to guidelines for magnetic resonance imaging in patients with multiple sclerosis (MS) are in the works to make the Consortium of Multiple Sclerosis Centers protocol and other international guidelines more similar, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.

“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.

The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
 

Standardizing scans

While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.

David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”

Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.

Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
 

Repositioning consistency is key

Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.

Central vein sign

Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.

“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”

Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
 

PML Surveillance

The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”

International protocol

Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.

Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”

In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.

However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”

“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”

The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.

Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

The Food and Drug Administration has approved Uplizna (inebilizumab-cdon) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-AQP4 antibody positive. Uplizna is the second approved treatment for the disorder.

Approval was based on results from the global, placebo-controlled N-MOmentum trial, which included 213 anti-AQP4 antibody–positive patients and 17 anti-AQP4 antibody–negative patients who received inebilizumab-cdon or placebo. Just under 90% of patients in the positive group remained relapse free 6 months after the initial dosing, compared with 58% of patients taking placebo. People who took inebilizumab also saw a reduction in NMOSD-related hospitalizations. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.

Inebilizumab-cdon was safe and well tolerated during the trial, with the most common adverse events being urinary tract infection (20%), nasopharyngitis (13%), infusion reaction (12%), arthralgia (11%), and headache (10%). The drug is approved as twice-yearly maintenance after initial dosing. The prescribing information for Uplizna includes a warning for infusion reactions, potential depletion of certain proteins (hypogammaglobulinemia), and potential increased risk of infection—including progressive multifocal leukoencephalopathy—and potential reactivation of hepatitis B and tuberculosis.

“NMOSD is an extremely challenging disease to treat. Patients experience unpredictable attacks that can lead to permanent disability from blindness and paralysis. In addition, each subsequent attack may result in a cumulative worsening of disability,” Bruce Cree, MD, PhD, lead investigator for the N-MOmentum trial and professor of clinical neurology at the University of California, San Francisco, said in a press release. “Uplizna is an important new treatment option that provides prescribing physicians and patients living with NMOSD a therapy with proven efficacy, a favorable safety profile and a twice-a-year maintenance dosing schedule.”

[email protected]

The Food and Drug Administration has approved Uplizna (inebilizumab-cdon) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-AQP4 antibody positive. Uplizna is the second approved treatment for the disorder.

Approval was based on results from the global, placebo-controlled N-MOmentum trial, which included 213 anti-AQP4 antibody–positive patients and 17 anti-AQP4 antibody–negative patients who received inebilizumab-cdon or placebo. Just under 90% of patients in the positive group remained relapse free 6 months after the initial dosing, compared with 58% of patients taking placebo. People who took inebilizumab also saw a reduction in NMOSD-related hospitalizations. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.

Inebilizumab-cdon was safe and well tolerated during the trial, with the most common adverse events being urinary tract infection (20%), nasopharyngitis (13%), infusion reaction (12%), arthralgia (11%), and headache (10%). The drug is approved as twice-yearly maintenance after initial dosing. The prescribing information for Uplizna includes a warning for infusion reactions, potential depletion of certain proteins (hypogammaglobulinemia), and potential increased risk of infection—including progressive multifocal leukoencephalopathy—and potential reactivation of hepatitis B and tuberculosis.

“NMOSD is an extremely challenging disease to treat. Patients experience unpredictable attacks that can lead to permanent disability from blindness and paralysis. In addition, each subsequent attack may result in a cumulative worsening of disability,” Bruce Cree, MD, PhD, lead investigator for the N-MOmentum trial and professor of clinical neurology at the University of California, San Francisco, said in a press release. “Uplizna is an important new treatment option that provides prescribing physicians and patients living with NMOSD a therapy with proven efficacy, a favorable safety profile and a twice-a-year maintenance dosing schedule.”

[email protected]

The Food and Drug Administration has approved Uplizna (inebilizumab-cdon) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-AQP4 antibody positive. Uplizna is the second approved treatment for the disorder.

Approval was based on results from the global, placebo-controlled N-MOmentum trial, which included 213 anti-AQP4 antibody–positive patients and 17 anti-AQP4 antibody–negative patients who received inebilizumab-cdon or placebo. Just under 90% of patients in the positive group remained relapse free 6 months after the initial dosing, compared with 58% of patients taking placebo. People who took inebilizumab also saw a reduction in NMOSD-related hospitalizations. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.

Inebilizumab-cdon was safe and well tolerated during the trial, with the most common adverse events being urinary tract infection (20%), nasopharyngitis (13%), infusion reaction (12%), arthralgia (11%), and headache (10%). The drug is approved as twice-yearly maintenance after initial dosing. The prescribing information for Uplizna includes a warning for infusion reactions, potential depletion of certain proteins (hypogammaglobulinemia), and potential increased risk of infection—including progressive multifocal leukoencephalopathy—and potential reactivation of hepatitis B and tuberculosis.

“NMOSD is an extremely challenging disease to treat. Patients experience unpredictable attacks that can lead to permanent disability from blindness and paralysis. In addition, each subsequent attack may result in a cumulative worsening of disability,” Bruce Cree, MD, PhD, lead investigator for the N-MOmentum trial and professor of clinical neurology at the University of California, San Francisco, said in a press release. “Uplizna is an important new treatment option that provides prescribing physicians and patients living with NMOSD a therapy with proven efficacy, a favorable safety profile and a twice-a-year maintenance dosing schedule.”

[email protected]

Despite the ever-increasing acceptance of medical cannabis and its notably common use in patients with multiple sclerosis (MS), clinicians treating those patients still may be poorly informed about risks, benefits, regulations, and proper uses, experts say.

“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.

As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
 

Misconceptions common among clinicians

Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.

Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.

In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.

Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.

There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.

Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.

Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.

And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.

Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.

However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.

Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.

However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.

He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.

While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.

“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
 

Addiction, distinguishing cannabis from MS symptoms

Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”

Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”

The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.

“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”

“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”

Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.

Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.

A version of this article originally appeared on Medscape.com.

Despite the ever-increasing acceptance of medical cannabis and its notably common use in patients with multiple sclerosis (MS), clinicians treating those patients still may be poorly informed about risks, benefits, regulations, and proper uses, experts say.

“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.

As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
 

Misconceptions common among clinicians

Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.

Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.

In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.

Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.

There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.

Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.

Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.

And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.

Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.

However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.

Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.

However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.

He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.

While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.

“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
 

Addiction, distinguishing cannabis from MS symptoms

Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”

Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”

The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.

“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”

“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”

Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.

Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.

A version of this article originally appeared on Medscape.com.

Despite the ever-increasing acceptance of medical cannabis and its notably common use in patients with multiple sclerosis (MS), clinicians treating those patients still may be poorly informed about risks, benefits, regulations, and proper uses, experts say.

“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.

As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
 

Misconceptions common among clinicians

Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.

Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.

In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.

Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.

There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.

Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.

Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.

And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.

Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.

However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.

Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.

However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.

He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.

While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.

“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
 

Addiction, distinguishing cannabis from MS symptoms

Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”

Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”

The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.

“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”

“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”

Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.

Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.

A version of this article originally appeared on Medscape.com.

The variability in functional performance within and between levels of disability measured by the Expanded Disability Status Scale (EDSS) call into question the reliability of the EDSS itself, according to researchers.

Preferred walking speed, for example, may vary by as much as 20% among patients with the same EDSS score. “Even though it is considered a walking scale, your scale defined groups of homogeneous disability are not even homogeneous for quantified measurement of walking ability,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y. “That’s a problem.”

Dr. Gudesblatt’s study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

John F. Kurtzke, MD, developed the EDSS in 1967. The scale has become a standard outcome of clinical trials, alongside MRI measures and annualized relapse rates. More than 15 therapies for MS have received regulatory approval in part based on their effects on EDSS outcomes. Furthermore, the recently proposed treatment goal of no evidence of disease activity includes the EDSS among its criteria.

Functional ability, however, which the EDSS measures, depends on various factors such as cognitive function, manual dexterity, and ambulation. If the degree of variability of these factors is greater than 20% within groups defined as having similar disability, this scale would no longer be valid, according to Dr. Gudesblatt.

To analyze the variability in functional performance in groups of patients with similar disability, Dr. Gudesblatt and colleagues retrospectively reviewed data from a prospective MS registry. Participants underwent multidimensional computerized cognitive testing and digital gait analysis. They also submitted patient-reported outcomes for hand function while undergoing simultaneous measurements of Patient-Determined Disease Steps (PDDS) or EDSS. For the analysis, Dr. Gudesblatt and colleagues defined groups of “adjacent” EDSS scores as follows: from 0 to 2.5, from 3 to 4.5, from 5 to 6.5, and greater than 7.

In all, 258 patients with MS underwent cognitive testing. Of this group, 73% of patients were women, and mean age was 46 years. The proportion of overlap in multidomain computerized cognitive testing global summary score of 7 domains among patients with adjacent EDSS scores was 65%. The researchers found 42% overlap among patients at the extremes of the EDSS scale. The proportion of overlap in accumulative cognitive impairment (i.e., the number of cognitive domains impaired by greater than one standard deviation) was 72% across adjacent EDSS groups and 38% across extreme EDSS groups.

Among 254 patients with MS who underwent evaluation of walking, 72% were women, and mean age was 46 years. The mean normalized velocity of preferred walking speed varied by more than 20% within EDSS groups and overlapped by more than 20% between groups.

A total of 783 patients underwent evaluation of hand function and tremor. About 74% of these participants were women, and mean age was 49 years. The variability across all PDDS groups (i.e., 0 to 1, 2 to 4, and greater than 4) was greater than 50%. Adjacent PDDS groups had overlap of more than 50%, and the extremes had an overlap of greater than 32%.

“The criteria for the diagnosis [of MS] have undergone multiple revisions, but the scale to define the disability remains unchanged,” said Dr. Gudesblatt. “It’s all about trying to do the right thing for the right patient at the right time for the right reason. We cannot go by our own perceptions. You need to have objective not subjective information to appropriately improve measurements of disease trajectory. The neurologist must move beyond the hammer and tuning fork, must move to objective, quantitative, examiner-independent, multidimensional measures of important aspects of disease to enhance identification of critical disease impact along a continuum so as to improved shared decision making with patient centric objective data to improve outcomes and reduce disability.”

Dr. Gudesblatt has served on speakers bureaus for Acorda, Amgen, Medtronic, and Saol Therapeutics. He has performed contracted research for Biogen, EMD Serono, Novartis, Sanofi, and Teva. The study was conducted without external funding.

[email protected]

SOURCE: Gudesblatt M et al. CMSC 2020. Abstract QOL15.

The variability in functional performance within and between levels of disability measured by the Expanded Disability Status Scale (EDSS) call into question the reliability of the EDSS itself, according to researchers.

Preferred walking speed, for example, may vary by as much as 20% among patients with the same EDSS score. “Even though it is considered a walking scale, your scale defined groups of homogeneous disability are not even homogeneous for quantified measurement of walking ability,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y. “That’s a problem.”

Dr. Gudesblatt’s study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

John F. Kurtzke, MD, developed the EDSS in 1967. The scale has become a standard outcome of clinical trials, alongside MRI measures and annualized relapse rates. More than 15 therapies for MS have received regulatory approval in part based on their effects on EDSS outcomes. Furthermore, the recently proposed treatment goal of no evidence of disease activity includes the EDSS among its criteria.

Functional ability, however, which the EDSS measures, depends on various factors such as cognitive function, manual dexterity, and ambulation. If the degree of variability of these factors is greater than 20% within groups defined as having similar disability, this scale would no longer be valid, according to Dr. Gudesblatt.

To analyze the variability in functional performance in groups of patients with similar disability, Dr. Gudesblatt and colleagues retrospectively reviewed data from a prospective MS registry. Participants underwent multidimensional computerized cognitive testing and digital gait analysis. They also submitted patient-reported outcomes for hand function while undergoing simultaneous measurements of Patient-Determined Disease Steps (PDDS) or EDSS. For the analysis, Dr. Gudesblatt and colleagues defined groups of “adjacent” EDSS scores as follows: from 0 to 2.5, from 3 to 4.5, from 5 to 6.5, and greater than 7.

In all, 258 patients with MS underwent cognitive testing. Of this group, 73% of patients were women, and mean age was 46 years. The proportion of overlap in multidomain computerized cognitive testing global summary score of 7 domains among patients with adjacent EDSS scores was 65%. The researchers found 42% overlap among patients at the extremes of the EDSS scale. The proportion of overlap in accumulative cognitive impairment (i.e., the number of cognitive domains impaired by greater than one standard deviation) was 72% across adjacent EDSS groups and 38% across extreme EDSS groups.

Among 254 patients with MS who underwent evaluation of walking, 72% were women, and mean age was 46 years. The mean normalized velocity of preferred walking speed varied by more than 20% within EDSS groups and overlapped by more than 20% between groups.

A total of 783 patients underwent evaluation of hand function and tremor. About 74% of these participants were women, and mean age was 49 years. The variability across all PDDS groups (i.e., 0 to 1, 2 to 4, and greater than 4) was greater than 50%. Adjacent PDDS groups had overlap of more than 50%, and the extremes had an overlap of greater than 32%.

“The criteria for the diagnosis [of MS] have undergone multiple revisions, but the scale to define the disability remains unchanged,” said Dr. Gudesblatt. “It’s all about trying to do the right thing for the right patient at the right time for the right reason. We cannot go by our own perceptions. You need to have objective not subjective information to appropriately improve measurements of disease trajectory. The neurologist must move beyond the hammer and tuning fork, must move to objective, quantitative, examiner-independent, multidimensional measures of important aspects of disease to enhance identification of critical disease impact along a continuum so as to improved shared decision making with patient centric objective data to improve outcomes and reduce disability.”

Dr. Gudesblatt has served on speakers bureaus for Acorda, Amgen, Medtronic, and Saol Therapeutics. He has performed contracted research for Biogen, EMD Serono, Novartis, Sanofi, and Teva. The study was conducted without external funding.

[email protected]

SOURCE: Gudesblatt M et al. CMSC 2020. Abstract QOL15.

The variability in functional performance within and between levels of disability measured by the Expanded Disability Status Scale (EDSS) call into question the reliability of the EDSS itself, according to researchers.

Preferred walking speed, for example, may vary by as much as 20% among patients with the same EDSS score. “Even though it is considered a walking scale, your scale defined groups of homogeneous disability are not even homogeneous for quantified measurement of walking ability,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y. “That’s a problem.”

Dr. Gudesblatt’s study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

John F. Kurtzke, MD, developed the EDSS in 1967. The scale has become a standard outcome of clinical trials, alongside MRI measures and annualized relapse rates. More than 15 therapies for MS have received regulatory approval in part based on their effects on EDSS outcomes. Furthermore, the recently proposed treatment goal of no evidence of disease activity includes the EDSS among its criteria.

Functional ability, however, which the EDSS measures, depends on various factors such as cognitive function, manual dexterity, and ambulation. If the degree of variability of these factors is greater than 20% within groups defined as having similar disability, this scale would no longer be valid, according to Dr. Gudesblatt.

To analyze the variability in functional performance in groups of patients with similar disability, Dr. Gudesblatt and colleagues retrospectively reviewed data from a prospective MS registry. Participants underwent multidimensional computerized cognitive testing and digital gait analysis. They also submitted patient-reported outcomes for hand function while undergoing simultaneous measurements of Patient-Determined Disease Steps (PDDS) or EDSS. For the analysis, Dr. Gudesblatt and colleagues defined groups of “adjacent” EDSS scores as follows: from 0 to 2.5, from 3 to 4.5, from 5 to 6.5, and greater than 7.

In all, 258 patients with MS underwent cognitive testing. Of this group, 73% of patients were women, and mean age was 46 years. The proportion of overlap in multidomain computerized cognitive testing global summary score of 7 domains among patients with adjacent EDSS scores was 65%. The researchers found 42% overlap among patients at the extremes of the EDSS scale. The proportion of overlap in accumulative cognitive impairment (i.e., the number of cognitive domains impaired by greater than one standard deviation) was 72% across adjacent EDSS groups and 38% across extreme EDSS groups.

Among 254 patients with MS who underwent evaluation of walking, 72% were women, and mean age was 46 years. The mean normalized velocity of preferred walking speed varied by more than 20% within EDSS groups and overlapped by more than 20% between groups.

A total of 783 patients underwent evaluation of hand function and tremor. About 74% of these participants were women, and mean age was 49 years. The variability across all PDDS groups (i.e., 0 to 1, 2 to 4, and greater than 4) was greater than 50%. Adjacent PDDS groups had overlap of more than 50%, and the extremes had an overlap of greater than 32%.

“The criteria for the diagnosis [of MS] have undergone multiple revisions, but the scale to define the disability remains unchanged,” said Dr. Gudesblatt. “It’s all about trying to do the right thing for the right patient at the right time for the right reason. We cannot go by our own perceptions. You need to have objective not subjective information to appropriately improve measurements of disease trajectory. The neurologist must move beyond the hammer and tuning fork, must move to objective, quantitative, examiner-independent, multidimensional measures of important aspects of disease to enhance identification of critical disease impact along a continuum so as to improved shared decision making with patient centric objective data to improve outcomes and reduce disability.”

Dr. Gudesblatt has served on speakers bureaus for Acorda, Amgen, Medtronic, and Saol Therapeutics. He has performed contracted research for Biogen, EMD Serono, Novartis, Sanofi, and Teva. The study was conducted without external funding.

[email protected]

SOURCE: Gudesblatt M et al. CMSC 2020. Abstract QOL15.

Key clinical point: Patients with relapsing-remitting multiple sclerosis (RRMS) having poor prognostic factors at baseline who were initiated with induction therapy have a lower risk for disability in the long term.

Major finding: After propensity matching, the proportion of patients reaching the primary outcome (Expanded Disability Status Scale [EDSS], ≥6.0) was lower in the induction group (28.0%) than the escalation group (38.7%). The median final EDSS scores were 5.0 and 4.5 after escalation and induction, respectively (P less than .001).

Study details: This study evaluated the long-term effectiveness of initial treatment with induction (n=75) or escalation (n=738) approach in patients with RRMS identified from a multicenter, retrospective registry database in Italy.

Disclosures: The authors declared no conflicts of interest.

Citation: Prosperini et al. Neurotherapeutics. 2020 Mar 31. doi: 10.1007/s13311-020-00847-0.

Key clinical point: Patients with relapsing-remitting multiple sclerosis (RRMS) having poor prognostic factors at baseline who were initiated with induction therapy have a lower risk for disability in the long term.

Major finding: After propensity matching, the proportion of patients reaching the primary outcome (Expanded Disability Status Scale [EDSS], ≥6.0) was lower in the induction group (28.0%) than the escalation group (38.7%). The median final EDSS scores were 5.0 and 4.5 after escalation and induction, respectively (P less than .001).

Study details: This study evaluated the long-term effectiveness of initial treatment with induction (n=75) or escalation (n=738) approach in patients with RRMS identified from a multicenter, retrospective registry database in Italy.

Disclosures: The authors declared no conflicts of interest.

Citation: Prosperini et al. Neurotherapeutics. 2020 Mar 31. doi: 10.1007/s13311-020-00847-0.

Key clinical point: Patients with relapsing-remitting multiple sclerosis (RRMS) having poor prognostic factors at baseline who were initiated with induction therapy have a lower risk for disability in the long term.

Major finding: After propensity matching, the proportion of patients reaching the primary outcome (Expanded Disability Status Scale [EDSS], ≥6.0) was lower in the induction group (28.0%) than the escalation group (38.7%). The median final EDSS scores were 5.0 and 4.5 after escalation and induction, respectively (P less than .001).

Study details: This study evaluated the long-term effectiveness of initial treatment with induction (n=75) or escalation (n=738) approach in patients with RRMS identified from a multicenter, retrospective registry database in Italy.

Disclosures: The authors declared no conflicts of interest.

Citation: Prosperini et al. Neurotherapeutics. 2020 Mar 31. doi: 10.1007/s13311-020-00847-0.

Key clinical point: A pro-inflammatory diet characterized by higher dietary inflammatory index (DII) and energy-adjusted DII (E-DII) during adolescence is a significant risk factor for the onset of multiple sclerosis (MS).

Major finding: The risks for MS increased significantly when E-DII was used as a continuous variable (adjusted odds ratio [aOR], 1.53; P = .001) and categorical variable (fourth vs. first quartile: aOR, 7.01; P less than .001). A similar pattern was seen for DII as both continuous and categorical variables.

Study details: This large population-based incident case-control study conducted in Iran included 547 patients with incident MS and 1057 individuals from the general population.

Disclosures: Dr Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company planning to license the DII from the University of South Carolina to develop computer and mobile applications. Dr Shivappa is an employee of CHI.

Citation: Abdollahpour I et al. Clin Nutr. 2020 Mar 6. doi: 10.1016/j.clnu.2020.02.033.

Key clinical point: A pro-inflammatory diet characterized by higher dietary inflammatory index (DII) and energy-adjusted DII (E-DII) during adolescence is a significant risk factor for the onset of multiple sclerosis (MS).

Major finding: The risks for MS increased significantly when E-DII was used as a continuous variable (adjusted odds ratio [aOR], 1.53; P = .001) and categorical variable (fourth vs. first quartile: aOR, 7.01; P less than .001). A similar pattern was seen for DII as both continuous and categorical variables.

Study details: This large population-based incident case-control study conducted in Iran included 547 patients with incident MS and 1057 individuals from the general population.

Disclosures: Dr Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company planning to license the DII from the University of South Carolina to develop computer and mobile applications. Dr Shivappa is an employee of CHI.

Citation: Abdollahpour I et al. Clin Nutr. 2020 Mar 6. doi: 10.1016/j.clnu.2020.02.033.

Key clinical point: A pro-inflammatory diet characterized by higher dietary inflammatory index (DII) and energy-adjusted DII (E-DII) during adolescence is a significant risk factor for the onset of multiple sclerosis (MS).

Major finding: The risks for MS increased significantly when E-DII was used as a continuous variable (adjusted odds ratio [aOR], 1.53; P = .001) and categorical variable (fourth vs. first quartile: aOR, 7.01; P less than .001). A similar pattern was seen for DII as both continuous and categorical variables.

Study details: This large population-based incident case-control study conducted in Iran included 547 patients with incident MS and 1057 individuals from the general population.

Disclosures: Dr Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company planning to license the DII from the University of South Carolina to develop computer and mobile applications. Dr Shivappa is an employee of CHI.

Citation: Abdollahpour I et al. Clin Nutr. 2020 Mar 6. doi: 10.1016/j.clnu.2020.02.033.

Key clinical point: In patients with multiple sclerosis (MS), protein concentrations of inflammatory cytokines, interleukin (IL)-27, transforming growth factor beta-1 (TGF-β1), and IL-10 are upregulated after 8 weeks of vitamin D₃ supplementation.

Major finding: In patients with MS, 8 weeks of vitamin D₃ administration upregulated the levels of IL-27 (P = .001), TGF-β1 (P less than .001), and IL-10 (P less than .001), whereas levels of IL-17A (P = .024) and IL-6 (P less than .001) were downregulated.

Study details: The study assessed venous blood samples drawn from individuals with MS (n=25) and control participants including first-degree relative (n=25) and healthy participants (n=25) before and after vitamin D₃ supplementation of 50,000 IU.

Disclosures: Dr SR Arefhosseini received financial support from Nutrition Research Center and Tabriz University of Medical Sciences, Tabriz, Iran.

Citation: Hashemi R et al. PLoS One. 2020 Apr 6. doi: 10.1371/journal.pone.0231145.

Key clinical point: In patients with multiple sclerosis (MS), protein concentrations of inflammatory cytokines, interleukin (IL)-27, transforming growth factor beta-1 (TGF-β1), and IL-10 are upregulated after 8 weeks of vitamin D₃ supplementation.

Major finding: In patients with MS, 8 weeks of vitamin D₃ administration upregulated the levels of IL-27 (P = .001), TGF-β1 (P less than .001), and IL-10 (P less than .001), whereas levels of IL-17A (P = .024) and IL-6 (P less than .001) were downregulated.

Study details: The study assessed venous blood samples drawn from individuals with MS (n=25) and control participants including first-degree relative (n=25) and healthy participants (n=25) before and after vitamin D₃ supplementation of 50,000 IU.

Disclosures: Dr SR Arefhosseini received financial support from Nutrition Research Center and Tabriz University of Medical Sciences, Tabriz, Iran.

Citation: Hashemi R et al. PLoS One. 2020 Apr 6. doi: 10.1371/journal.pone.0231145.

Key clinical point: In patients with multiple sclerosis (MS), protein concentrations of inflammatory cytokines, interleukin (IL)-27, transforming growth factor beta-1 (TGF-β1), and IL-10 are upregulated after 8 weeks of vitamin D₃ supplementation.

Major finding: In patients with MS, 8 weeks of vitamin D₃ administration upregulated the levels of IL-27 (P = .001), TGF-β1 (P less than .001), and IL-10 (P less than .001), whereas levels of IL-17A (P = .024) and IL-6 (P less than .001) were downregulated.

Study details: The study assessed venous blood samples drawn from individuals with MS (n=25) and control participants including first-degree relative (n=25) and healthy participants (n=25) before and after vitamin D₃ supplementation of 50,000 IU.

Disclosures: Dr SR Arefhosseini received financial support from Nutrition Research Center and Tabriz University of Medical Sciences, Tabriz, Iran.

Citation: Hashemi R et al. PLoS One. 2020 Apr 6. doi: 10.1371/journal.pone.0231145.

Key clinical point: Study finds direct evidence of transient neurotoxicity immediately after immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for aggressive multiple sclerosis (MS).

Major finding: Three months post-IAHSCT, levels of serum markers of both neuroaxonal and glial cell injury (serum Neurofilament Light Chain [sNfL] and serum Glial Fibrillary Acidic Protein [sGFAP]) increased from baseline by 32.1% (P = .029) and 74.8% (P = .0004), respectively. sNfL increases correlated with the dose of busulfan administered during transplant conditioning (P = .034), Expanded Disability Status Scale score (P = .041), as well as brain volume loss (P = .044), attributed to gray matter loss (P = .0023).

Study details: sNfL and sGFAP levels were evaluated pre- and post-IAHSCT at 3, 6, 9, and 12 months in 22 patients with MS and 28 noninflammatory control participants.

Disclosures: The study was funded by the MS Society of Canada. The authors declared no conflict of interest.

Citation: Thebault S et al. Ann Clin Transl Neurol. 2020 Apr 18. doi: 10.1002/acn3.51045.

Key clinical point: Study finds direct evidence of transient neurotoxicity immediately after immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for aggressive multiple sclerosis (MS).

Major finding: Three months post-IAHSCT, levels of serum markers of both neuroaxonal and glial cell injury (serum Neurofilament Light Chain [sNfL] and serum Glial Fibrillary Acidic Protein [sGFAP]) increased from baseline by 32.1% (P = .029) and 74.8% (P = .0004), respectively. sNfL increases correlated with the dose of busulfan administered during transplant conditioning (P = .034), Expanded Disability Status Scale score (P = .041), as well as brain volume loss (P = .044), attributed to gray matter loss (P = .0023).

Study details: sNfL and sGFAP levels were evaluated pre- and post-IAHSCT at 3, 6, 9, and 12 months in 22 patients with MS and 28 noninflammatory control participants.

Disclosures: The study was funded by the MS Society of Canada. The authors declared no conflict of interest.

Citation: Thebault S et al. Ann Clin Transl Neurol. 2020 Apr 18. doi: 10.1002/acn3.51045.

Key clinical point: Study finds direct evidence of transient neurotoxicity immediately after immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for aggressive multiple sclerosis (MS).

Major finding: Three months post-IAHSCT, levels of serum markers of both neuroaxonal and glial cell injury (serum Neurofilament Light Chain [sNfL] and serum Glial Fibrillary Acidic Protein [sGFAP]) increased from baseline by 32.1% (P = .029) and 74.8% (P = .0004), respectively. sNfL increases correlated with the dose of busulfan administered during transplant conditioning (P = .034), Expanded Disability Status Scale score (P = .041), as well as brain volume loss (P = .044), attributed to gray matter loss (P = .0023).

Study details: sNfL and sGFAP levels were evaluated pre- and post-IAHSCT at 3, 6, 9, and 12 months in 22 patients with MS and 28 noninflammatory control participants.

Disclosures: The study was funded by the MS Society of Canada. The authors declared no conflict of interest.

Citation: Thebault S et al. Ann Clin Transl Neurol. 2020 Apr 18. doi: 10.1002/acn3.51045.