Multiple Sclerosis

Key clinical point: Plasma neurofilament light chain (pNfL) could serve as an effective biomarker for identifying disability progression and monitoring treatment response in progressive multiple sclerosis (PMS).

Major finding: High vs. low pNfL levels increased the risk for 3-month confirmed disability progression (CDP) by 32% (P = .0055) and 49% (P = .0268) and 6-month CDP by 26% (P = .0417) and 48% (P = .0431) in patients with secondary PMS (SPMS) and primary PMS (PPMS), respectively. pNfL levels were lower in patients treated with siponimod or fingolimod vs. placebo.

Study details: This was a post hoc analysis of EXPAND and INFORMS studies including 1452 and 378 patients with SPMS and PPMS, respectively, who received siponimod, fingolimod, or placebo.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Some authors, including the lead author, reported being current or former employees of Novartis Pharma AG and some authors reported serving on advisory boards or receiving grants, speaker honoraria, lecture fees, or consulting fees from various sources, including Novartis Pharma AG.

Source: Leppert D et al. blood neurofilament light in progressive multiple sclerosis: Post hoc analysis of 2 randomized controlled trials. Neurology. 2022 (Apr 4). Doi: 10.1212/WNL.0000000000200258

Key clinical point: Plasma neurofilament light chain (pNfL) could serve as an effective biomarker for identifying disability progression and monitoring treatment response in progressive multiple sclerosis (PMS).

Major finding: High vs. low pNfL levels increased the risk for 3-month confirmed disability progression (CDP) by 32% (P = .0055) and 49% (P = .0268) and 6-month CDP by 26% (P = .0417) and 48% (P = .0431) in patients with secondary PMS (SPMS) and primary PMS (PPMS), respectively. pNfL levels were lower in patients treated with siponimod or fingolimod vs. placebo.

Study details: This was a post hoc analysis of EXPAND and INFORMS studies including 1452 and 378 patients with SPMS and PPMS, respectively, who received siponimod, fingolimod, or placebo.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Some authors, including the lead author, reported being current or former employees of Novartis Pharma AG and some authors reported serving on advisory boards or receiving grants, speaker honoraria, lecture fees, or consulting fees from various sources, including Novartis Pharma AG.

Source: Leppert D et al. blood neurofilament light in progressive multiple sclerosis: Post hoc analysis of 2 randomized controlled trials. Neurology. 2022 (Apr 4). Doi: 10.1212/WNL.0000000000200258

Key clinical point: Plasma neurofilament light chain (pNfL) could serve as an effective biomarker for identifying disability progression and monitoring treatment response in progressive multiple sclerosis (PMS).

Major finding: High vs. low pNfL levels increased the risk for 3-month confirmed disability progression (CDP) by 32% (P = .0055) and 49% (P = .0268) and 6-month CDP by 26% (P = .0417) and 48% (P = .0431) in patients with secondary PMS (SPMS) and primary PMS (PPMS), respectively. pNfL levels were lower in patients treated with siponimod or fingolimod vs. placebo.

Study details: This was a post hoc analysis of EXPAND and INFORMS studies including 1452 and 378 patients with SPMS and PPMS, respectively, who received siponimod, fingolimod, or placebo.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Some authors, including the lead author, reported being current or former employees of Novartis Pharma AG and some authors reported serving on advisory boards or receiving grants, speaker honoraria, lecture fees, or consulting fees from various sources, including Novartis Pharma AG.

Source: Leppert D et al. blood neurofilament light in progressive multiple sclerosis: Post hoc analysis of 2 randomized controlled trials. Neurology. 2022 (Apr 4). Doi: 10.1212/WNL.0000000000200258

Key clinical point: The average relapse rates and the rate of severe relapses did not increase significantly after fingolimod discontinuation in patients with relapsing multiple sclerosis (MS); however, delaying the commencement of immunotherapy increased the risk for relapse.

Major finding: The annualized relapse rate (ARR) was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior and after fingolimod cessation. However, delaying the recommencement of therapy from 2 to 4 months vs. beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse.

Study details: Findings are from an analysis of 685 patients with relapsing MS who received fingolimod therapy for at least 12 months and were followed-up for at least 12 months after fingolimod cessation.

Disclosures: Open access funding was enabled by CAUL and its member institutions. Some authors declared receiving research support, personal compensation, speaker or consulting fees, or nonfinancial support from various sources.

Source: Malpas CB et al. Multiple sclerosis relapses following cessation of fingolimod. Clin Drug Investig. 2022;42:355-364 (Mar 18). Doi: 10.1007/s40261-022-01129-7

Key clinical point: The average relapse rates and the rate of severe relapses did not increase significantly after fingolimod discontinuation in patients with relapsing multiple sclerosis (MS); however, delaying the commencement of immunotherapy increased the risk for relapse.

Major finding: The annualized relapse rate (ARR) was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior and after fingolimod cessation. However, delaying the recommencement of therapy from 2 to 4 months vs. beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse.

Study details: Findings are from an analysis of 685 patients with relapsing MS who received fingolimod therapy for at least 12 months and were followed-up for at least 12 months after fingolimod cessation.

Disclosures: Open access funding was enabled by CAUL and its member institutions. Some authors declared receiving research support, personal compensation, speaker or consulting fees, or nonfinancial support from various sources.

Source: Malpas CB et al. Multiple sclerosis relapses following cessation of fingolimod. Clin Drug Investig. 2022;42:355-364 (Mar 18). Doi: 10.1007/s40261-022-01129-7

Key clinical point: The average relapse rates and the rate of severe relapses did not increase significantly after fingolimod discontinuation in patients with relapsing multiple sclerosis (MS); however, delaying the commencement of immunotherapy increased the risk for relapse.

Major finding: The annualized relapse rate (ARR) was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior and after fingolimod cessation. However, delaying the recommencement of therapy from 2 to 4 months vs. beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse.

Study details: Findings are from an analysis of 685 patients with relapsing MS who received fingolimod therapy for at least 12 months and were followed-up for at least 12 months after fingolimod cessation.

Disclosures: Open access funding was enabled by CAUL and its member institutions. Some authors declared receiving research support, personal compensation, speaker or consulting fees, or nonfinancial support from various sources.

Source: Malpas CB et al. Multiple sclerosis relapses following cessation of fingolimod. Clin Drug Investig. 2022;42:355-364 (Mar 18). Doi: 10.1007/s40261-022-01129-7

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

Dr. Obeidat is an Assistant Professor in the Department of Neurology, 

Neuroimmunology and Multiple Sclerosis and is the Founding Director of the Neuroimmunology and MS Fellowship Program at The Medical College of Wisconsin in Milwaukee, WI.

Dr. Obeidat reports having consulted with/spoken for/conducted clinical trials for AbbVie, Alexion, Atara Biotherapeutics, Biogen, Bristol-Myers Squibb, Central, Celgene, EMD Serono, GW Pharmaceuticals, Genentech, Horizon, Jazz Pharma, Novartis, Sanofi/Genzyme, TG Therapeutics, and Viela Bio. Dr. Obeidat serves on the editorial board of the International Journal of MS Care, the advisory board of Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS®), and the Board of Governors of the Consortium of Multiple Sclerosis Centers.

“Could multiple sclerosis be the direct result of a yet-to-be identified infection?” asked John Kurtzke, MD, of his audience during his Grand Rounds entitled “Epidemiology and the Cause of Multiple Sclerosis” at the National Institute of Health (NIH) in 2015.¹ As a pioneer of neuroepidemiology, Dr Kurtzke had long considered that infection was a key step in the development of multiple sclerosis (MS), the most disabling nontraumatic neurologic disease in young adults. He and others, from the 1970s onwards, described disease outbreaks and patterns of disease distribution in various countries during periods of immigration and even wartime.^1,2 

A half century later and Dr Kurtzke’s question has a possible answer: The Epstein-Barr virus (EBV), a gamma herpes virus responsible for mononucleosis that has been long suspected as a link to the development of MS,³ is now more than a virus of interest. A longitudinal study pinpointed the virus’ almost universal presence in patients with MS.⁴ Not everyone who develops mononucleosis from EBV develops MS, but most people become infected with EBV at some point in their lives. EBV is highly prevalent in the general population, with some studies suggesting that more than 90% of people worldwide are infected with EBV.⁵ While the discovery raises many questions about MS etiology and disease progression, it also allows discussion on more therapeutic possibilities.

MS Numbers

With nearly 1 million people in the United States living with MS, and over 2.5 million people worldwide, MS has been the subject of numerous investigations.² Its complexity and heterogeneity have gained significant interest from the scientific community, including from Dr. Kurtzke, who passed away the same year as his NIH presentation.1

Several investigators over the years have attempted to link viral infections to MS,³ especially EBV. In February 2022, a longitudinal study spanning 20 years shed additional light on this longstanding, controversial, heavily researched potential association.⁴ The collaborative group of investigators used a database of serial blood samples from more than 10 million active US military personnel to investigate the association between EBV and MS and to learn whether EBV infection preceded the development of MS. 

Out of 801 persons with a documented diagnosis of MS in this study, only 1 case occurred in a person who tested negative for EBV infection.⁴ At baseline, 35 people with MS tested negative for EBV infection, but after receiving their MS diagnosis, they tested positive for the virus,  suggesting a causal relationship between EBV and MS. The study also showed that the levels of serum neurofilament light (sNfL), a nonspecific biomarker indicative of neuroaxonal injury or degeneration, increased post-EBV infection in the sera of initially EBV-negative patients with MS.⁴ This raises the question again: Why do only a small subset of people with EBV develop MS?

Facts and Questions

MS is a complex, heterogeneous disease whose development would require more than a human gamma herpesvirus to directly trigger its life-long, unrelenting immune dysregulation in select people. The complexity, which has been reviewed in detail, 6 suggests a role for interaction between host genetics, vitamin D levels, vitamin D receptors, and a specific protein of EBV, called Epstein-Barr nuclear antigen 1 (EBNA1).6 A recent publication described the potential for molecular mimicry (also known as cross-reactivity) between (EBNA1)⁶ and a specific cell adhesion molecule expressed in glial cells of the central nervous system (GlialCAM).⁷ 

But this molecular mimicry is not sufficient to explain the EBV/MS relationship. Even in monozygotic twins, the concordance rate is around 25%, leaving three-fourths of the risk of MS to the environment and genetics-environment interaction.⁸ The chances for monozygotic twins to both be infected with EBV are estimated at much more than 25%, given the epidemiology of EBV. Thus, EBV infection combined with specific genetic susceptibility remains insufficient to explain the observed epidemiology of MS. 

More Factors

Several investigators have reported on the association between low vitamin D levels and MS. Low vitamin D is thought to affect both disease development and inflammatory activity.⁹ So, does MS result from the interaction between EBV, genetics, and low vitamin D? This interaction is plausible and is supported by several lines of evidence^.6 However, even the interaction between these 3 factors remains insufficient to explain the complexity of MS pathogenesis. 

An Unknown Mechanism

The triggering mechanism from EBV into MS remains an open question, and further research is needed. Nevertheless, if infection by EBV is a necessary, yet insufficient, step for MS to occur, can we prevent MS simply by preventing the primary EBV infection via vaccination? If so, what considerations must we make? For example, if EBV infection triggers MS via the transformation of infected memory B cells, thereby triggering an autoreactive immune response, then a vaccine capable of preventing the primary EBV infection could reduce the number of new MS cases, or ambitiously eradicate the disease itself. On the other hand, if molecular mimicry is the leading mechanism by which EBV infection triggers MS, then an EBV vaccine may have detrimental effects and theoretically trigger MS in susceptible individuals. Thus, it is of utmost importance to clearly understand how EBV infection contributes to MS pathogenesis to evaluate potential EBV vaccine candidates. 

Treatment Possibilities

What are some possible clinical implications for the EBV-MS story for people living with MS? An important consideration is whether latent EBV infection contributes to the disease process over time, or if the infection is just an initial step that triggers numerous events that then operate independently from the virus. Suppose latent EBV infection contributes to the ongoing inflammatory and neurodegenerative changes in MS. In that case, some may consider using antiviral therapies as possible therapeutics for MS (possibly as an add-on, in combination with existing or future classes of disease-modifying therapies). Other interventions targeted at infected, transformed, or autoreactive B cells may bring us closer to precision medicine in MS. On the other hand, if the role of EBV is mainly to kick off MS, then further interventions targeted at the virus may not prove to be clinically effective.

Finally, the recent evidence of possible molecular mimicry to support causality between EBV infection and MS needs further investigation to elucidate how a common, ubiquitous infection kicks off MS in selected individuals. Additionally, the complex interactions between EBV, the human immune system, and genetics, as well as with other factors such as emotional stress,¹⁰  low sun exposure,11 and other, yet-to-be-identified environmental factors, may add more pieces to the complex etiology puzzle of MS and perhaps allow for effective interventions to help reduce the incidence of MS and even modulate disease progression.

Dr. Obeidat is an Assistant Professor in the Department of Neurology, 

Neuroimmunology and Multiple Sclerosis and is the Founding Director of the Neuroimmunology and MS Fellowship Program at The Medical College of Wisconsin in Milwaukee, WI.

Dr. Obeidat reports having consulted with/spoken for/conducted clinical trials for AbbVie, Alexion, Atara Biotherapeutics, Biogen, Bristol-Myers Squibb, Central, Celgene, EMD Serono, GW Pharmaceuticals, Genentech, Horizon, Jazz Pharma, Novartis, Sanofi/Genzyme, TG Therapeutics, and Viela Bio. Dr. Obeidat serves on the editorial board of the International Journal of MS Care, the advisory board of Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS®), and the Board of Governors of the Consortium of Multiple Sclerosis Centers.

“Could multiple sclerosis be the direct result of a yet-to-be identified infection?” asked John Kurtzke, MD, of his audience during his Grand Rounds entitled “Epidemiology and the Cause of Multiple Sclerosis” at the National Institute of Health (NIH) in 2015.¹ As a pioneer of neuroepidemiology, Dr Kurtzke had long considered that infection was a key step in the development of multiple sclerosis (MS), the most disabling nontraumatic neurologic disease in young adults. He and others, from the 1970s onwards, described disease outbreaks and patterns of disease distribution in various countries during periods of immigration and even wartime.^1,2 

A half century later and Dr Kurtzke’s question has a possible answer: The Epstein-Barr virus (EBV), a gamma herpes virus responsible for mononucleosis that has been long suspected as a link to the development of MS,³ is now more than a virus of interest. A longitudinal study pinpointed the virus’ almost universal presence in patients with MS.⁴ Not everyone who develops mononucleosis from EBV develops MS, but most people become infected with EBV at some point in their lives. EBV is highly prevalent in the general population, with some studies suggesting that more than 90% of people worldwide are infected with EBV.⁵ While the discovery raises many questions about MS etiology and disease progression, it also allows discussion on more therapeutic possibilities.

MS Numbers

With nearly 1 million people in the United States living with MS, and over 2.5 million people worldwide, MS has been the subject of numerous investigations.² Its complexity and heterogeneity have gained significant interest from the scientific community, including from Dr. Kurtzke, who passed away the same year as his NIH presentation.1

Several investigators over the years have attempted to link viral infections to MS,³ especially EBV. In February 2022, a longitudinal study spanning 20 years shed additional light on this longstanding, controversial, heavily researched potential association.⁴ The collaborative group of investigators used a database of serial blood samples from more than 10 million active US military personnel to investigate the association between EBV and MS and to learn whether EBV infection preceded the development of MS. 

Out of 801 persons with a documented diagnosis of MS in this study, only 1 case occurred in a person who tested negative for EBV infection.⁴ At baseline, 35 people with MS tested negative for EBV infection, but after receiving their MS diagnosis, they tested positive for the virus,  suggesting a causal relationship between EBV and MS. The study also showed that the levels of serum neurofilament light (sNfL), a nonspecific biomarker indicative of neuroaxonal injury or degeneration, increased post-EBV infection in the sera of initially EBV-negative patients with MS.⁴ This raises the question again: Why do only a small subset of people with EBV develop MS?

Facts and Questions

MS is a complex, heterogeneous disease whose development would require more than a human gamma herpesvirus to directly trigger its life-long, unrelenting immune dysregulation in select people. The complexity, which has been reviewed in detail, 6 suggests a role for interaction between host genetics, vitamin D levels, vitamin D receptors, and a specific protein of EBV, called Epstein-Barr nuclear antigen 1 (EBNA1).6 A recent publication described the potential for molecular mimicry (also known as cross-reactivity) between (EBNA1)⁶ and a specific cell adhesion molecule expressed in glial cells of the central nervous system (GlialCAM).⁷ 

But this molecular mimicry is not sufficient to explain the EBV/MS relationship. Even in monozygotic twins, the concordance rate is around 25%, leaving three-fourths of the risk of MS to the environment and genetics-environment interaction.⁸ The chances for monozygotic twins to both be infected with EBV are estimated at much more than 25%, given the epidemiology of EBV. Thus, EBV infection combined with specific genetic susceptibility remains insufficient to explain the observed epidemiology of MS. 

More Factors

Several investigators have reported on the association between low vitamin D levels and MS. Low vitamin D is thought to affect both disease development and inflammatory activity.⁹ So, does MS result from the interaction between EBV, genetics, and low vitamin D? This interaction is plausible and is supported by several lines of evidence^.6 However, even the interaction between these 3 factors remains insufficient to explain the complexity of MS pathogenesis. 

An Unknown Mechanism

The triggering mechanism from EBV into MS remains an open question, and further research is needed. Nevertheless, if infection by EBV is a necessary, yet insufficient, step for MS to occur, can we prevent MS simply by preventing the primary EBV infection via vaccination? If so, what considerations must we make? For example, if EBV infection triggers MS via the transformation of infected memory B cells, thereby triggering an autoreactive immune response, then a vaccine capable of preventing the primary EBV infection could reduce the number of new MS cases, or ambitiously eradicate the disease itself. On the other hand, if molecular mimicry is the leading mechanism by which EBV infection triggers MS, then an EBV vaccine may have detrimental effects and theoretically trigger MS in susceptible individuals. Thus, it is of utmost importance to clearly understand how EBV infection contributes to MS pathogenesis to evaluate potential EBV vaccine candidates. 

Treatment Possibilities

What are some possible clinical implications for the EBV-MS story for people living with MS? An important consideration is whether latent EBV infection contributes to the disease process over time, or if the infection is just an initial step that triggers numerous events that then operate independently from the virus. Suppose latent EBV infection contributes to the ongoing inflammatory and neurodegenerative changes in MS. In that case, some may consider using antiviral therapies as possible therapeutics for MS (possibly as an add-on, in combination with existing or future classes of disease-modifying therapies). Other interventions targeted at infected, transformed, or autoreactive B cells may bring us closer to precision medicine in MS. On the other hand, if the role of EBV is mainly to kick off MS, then further interventions targeted at the virus may not prove to be clinically effective.

Finally, the recent evidence of possible molecular mimicry to support causality between EBV infection and MS needs further investigation to elucidate how a common, ubiquitous infection kicks off MS in selected individuals. Additionally, the complex interactions between EBV, the human immune system, and genetics, as well as with other factors such as emotional stress,¹⁰  low sun exposure,11 and other, yet-to-be-identified environmental factors, may add more pieces to the complex etiology puzzle of MS and perhaps allow for effective interventions to help reduce the incidence of MS and even modulate disease progression.

Dr. Obeidat is an Assistant Professor in the Department of Neurology, 

Neuroimmunology and Multiple Sclerosis and is the Founding Director of the Neuroimmunology and MS Fellowship Program at The Medical College of Wisconsin in Milwaukee, WI.

Dr. Obeidat reports having consulted with/spoken for/conducted clinical trials for AbbVie, Alexion, Atara Biotherapeutics, Biogen, Bristol-Myers Squibb, Central, Celgene, EMD Serono, GW Pharmaceuticals, Genentech, Horizon, Jazz Pharma, Novartis, Sanofi/Genzyme, TG Therapeutics, and Viela Bio. Dr. Obeidat serves on the editorial board of the International Journal of MS Care, the advisory board of Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS®), and the Board of Governors of the Consortium of Multiple Sclerosis Centers.

“Could multiple sclerosis be the direct result of a yet-to-be identified infection?” asked John Kurtzke, MD, of his audience during his Grand Rounds entitled “Epidemiology and the Cause of Multiple Sclerosis” at the National Institute of Health (NIH) in 2015.¹ As a pioneer of neuroepidemiology, Dr Kurtzke had long considered that infection was a key step in the development of multiple sclerosis (MS), the most disabling nontraumatic neurologic disease in young adults. He and others, from the 1970s onwards, described disease outbreaks and patterns of disease distribution in various countries during periods of immigration and even wartime.^1,2 

A half century later and Dr Kurtzke’s question has a possible answer: The Epstein-Barr virus (EBV), a gamma herpes virus responsible for mononucleosis that has been long suspected as a link to the development of MS,³ is now more than a virus of interest. A longitudinal study pinpointed the virus’ almost universal presence in patients with MS.⁴ Not everyone who develops mononucleosis from EBV develops MS, but most people become infected with EBV at some point in their lives. EBV is highly prevalent in the general population, with some studies suggesting that more than 90% of people worldwide are infected with EBV.⁵ While the discovery raises many questions about MS etiology and disease progression, it also allows discussion on more therapeutic possibilities.

MS Numbers

With nearly 1 million people in the United States living with MS, and over 2.5 million people worldwide, MS has been the subject of numerous investigations.² Its complexity and heterogeneity have gained significant interest from the scientific community, including from Dr. Kurtzke, who passed away the same year as his NIH presentation.1

Several investigators over the years have attempted to link viral infections to MS,³ especially EBV. In February 2022, a longitudinal study spanning 20 years shed additional light on this longstanding, controversial, heavily researched potential association.⁴ The collaborative group of investigators used a database of serial blood samples from more than 10 million active US military personnel to investigate the association between EBV and MS and to learn whether EBV infection preceded the development of MS. 

Out of 801 persons with a documented diagnosis of MS in this study, only 1 case occurred in a person who tested negative for EBV infection.⁴ At baseline, 35 people with MS tested negative for EBV infection, but after receiving their MS diagnosis, they tested positive for the virus,  suggesting a causal relationship between EBV and MS. The study also showed that the levels of serum neurofilament light (sNfL), a nonspecific biomarker indicative of neuroaxonal injury or degeneration, increased post-EBV infection in the sera of initially EBV-negative patients with MS.⁴ This raises the question again: Why do only a small subset of people with EBV develop MS?

Facts and Questions

MS is a complex, heterogeneous disease whose development would require more than a human gamma herpesvirus to directly trigger its life-long, unrelenting immune dysregulation in select people. The complexity, which has been reviewed in detail, 6 suggests a role for interaction between host genetics, vitamin D levels, vitamin D receptors, and a specific protein of EBV, called Epstein-Barr nuclear antigen 1 (EBNA1).6 A recent publication described the potential for molecular mimicry (also known as cross-reactivity) between (EBNA1)⁶ and a specific cell adhesion molecule expressed in glial cells of the central nervous system (GlialCAM).⁷ 

But this molecular mimicry is not sufficient to explain the EBV/MS relationship. Even in monozygotic twins, the concordance rate is around 25%, leaving three-fourths of the risk of MS to the environment and genetics-environment interaction.⁸ The chances for monozygotic twins to both be infected with EBV are estimated at much more than 25%, given the epidemiology of EBV. Thus, EBV infection combined with specific genetic susceptibility remains insufficient to explain the observed epidemiology of MS. 

More Factors

Several investigators have reported on the association between low vitamin D levels and MS. Low vitamin D is thought to affect both disease development and inflammatory activity.⁹ So, does MS result from the interaction between EBV, genetics, and low vitamin D? This interaction is plausible and is supported by several lines of evidence^.6 However, even the interaction between these 3 factors remains insufficient to explain the complexity of MS pathogenesis. 

An Unknown Mechanism

The triggering mechanism from EBV into MS remains an open question, and further research is needed. Nevertheless, if infection by EBV is a necessary, yet insufficient, step for MS to occur, can we prevent MS simply by preventing the primary EBV infection via vaccination? If so, what considerations must we make? For example, if EBV infection triggers MS via the transformation of infected memory B cells, thereby triggering an autoreactive immune response, then a vaccine capable of preventing the primary EBV infection could reduce the number of new MS cases, or ambitiously eradicate the disease itself. On the other hand, if molecular mimicry is the leading mechanism by which EBV infection triggers MS, then an EBV vaccine may have detrimental effects and theoretically trigger MS in susceptible individuals. Thus, it is of utmost importance to clearly understand how EBV infection contributes to MS pathogenesis to evaluate potential EBV vaccine candidates. 

Treatment Possibilities

What are some possible clinical implications for the EBV-MS story for people living with MS? An important consideration is whether latent EBV infection contributes to the disease process over time, or if the infection is just an initial step that triggers numerous events that then operate independently from the virus. Suppose latent EBV infection contributes to the ongoing inflammatory and neurodegenerative changes in MS. In that case, some may consider using antiviral therapies as possible therapeutics for MS (possibly as an add-on, in combination with existing or future classes of disease-modifying therapies). Other interventions targeted at infected, transformed, or autoreactive B cells may bring us closer to precision medicine in MS. On the other hand, if the role of EBV is mainly to kick off MS, then further interventions targeted at the virus may not prove to be clinically effective.

Finally, the recent evidence of possible molecular mimicry to support causality between EBV infection and MS needs further investigation to elucidate how a common, ubiquitous infection kicks off MS in selected individuals. Additionally, the complex interactions between EBV, the human immune system, and genetics, as well as with other factors such as emotional stress,¹⁰  low sun exposure,11 and other, yet-to-be-identified environmental factors, may add more pieces to the complex etiology puzzle of MS and perhaps allow for effective interventions to help reduce the incidence of MS and even modulate disease progression.

SEATTLE – Multiple sclerosis (MS), sometimes thought of as primarily affecting Whites, is also common among Hispanic and Black people. These populations often have more severe disease, likely driven by socioeconomic factors and health care access, according to a new study that examined neighborhood-level data and disease severity in the United States.

“It has previously been thought that MS is less common among non-European Caucasian White populations, driven partly by the well-known association of incidence with latitude. It is abundantly clear at this point that this idea is not true,” said Christopher Orlando, MD, during a presentation at the 2022 annual meeting of the American Academy of Neurology.

He noted that several U.S. studies with large sample sizes have shown greater disease severity and a higher disability burden among Hispanic and Black patients. “Black patients in particular appear to have a higher incidence of disease and a greater proportion of progressive disease phenotypes,” said Dr. Orlando.

Race and ethnicity are unlikely explanations for this disparity, according to Dr. Orlando. “While much remains to be discovered of the genetic underpinnings of MS, what we do know does not support the idea that minorities would have a predilection to more severe disease. For example, the well-known high-risk allele HLA DRB1*1501 appears to have a lower frequency in African populations, compared with European [populations].”

Instead, evidence suggests that interrelated social causes include access to resources, environmental exposures, and psychosocial stress. “These affect health via a number of pathways including direct physical injury, allostatic load, and access to health care,” said Dr. Orlando.
 

Probing racial and ethnic disparities

Previous studies that corrected for social determinants of health such as socioeconomic and insurance status reduce the association between MS disability and race, but they do not completely explain it.

To get a better understanding of the impacts of these factors, researchers have used neighborhood-level data combined with information on socioeconomic status and social deprivation to identify associations with MS severity.

At the conference, Dr. Orlando presented a new study that is the first to use this methodology in the United States, and it is the first to apply it to the study of racial and ethnic disparities in MS.

The study confirmed more severe disability in Hispanic and Black patients than in White patients. Clinical factors associated with more severe disease were similar across the three groups, with some small differences among individual traits. “More stark differences appeared when we compared social determinants of health. Hispanic patients were less likely to speak English as a primary language or to complete 12 years of education. Black patients were less likely to live in a rural county and more likely to be unemployed. One particularly stark difference was in the number of unemployed specifically due to their MS, with only 1 White patient [1.1%], 7 Hispanic patients [7.8%] and 27 Black patients [31.0%],” said Dr. Orlando.

The researchers found that Black and Hispanic patients tend to live in more vulnerable neighborhoods than White patients. The researchers found no significant association between social vulnerability index (SVI) values and MS severity, though there was an association in a separate analysis that only included White patients. The SVI uses 15 measures taken from the U.S. Census to identify communities that might require additional support during natural disasters.

“It would appear that the sheer complexity both in variety and magnitude of the social determinants of health are such that by far the stronger association is with race and ethnicity, which are surrogates for any number of social determinants and societal inequities,” said Dr. Orlando.
 

What drives the inequity?

Dr. Orlando acknowledged that some might wonder if these results indicate a true biologically intrinsic factor such as genetic predisposition. “I want to warn against that kind of thinking in the strongest possible terms. It is implausible on several levels. It’s not biologically plausible based on our understanding that race and ethnicity are not genetic constructs. And it’s also not numerically plausible based on these data,” said Dr. Orlando.

While some of the drivers of this inequity have been partially examined, many have not been studied. “As long as this is the case, our ability to fulfill our roles as physicians will be limited in several important ways. Our ability to assess our patients’ individual risk will be missing key information, which will limit the efficacy of shared decision-making, which of course is the cornerstone of MS treatment. In addition, we will continue to struggle to include minority patients in our research studies, and the very design and results of those studies may be misguided, as we will either fail to include these populations, or we will fail to adjust for important confounders,” he said.
 

New answers, new questions

The neighborhood-level data examined by Dr. Orlando’s group “brings extra information in terms of the negative impact of social determinants of health. The disparity seen in neighborhood living is quite striking,” said Lilyana Amezcua, MD, who served as a discussant for Dr. Orlando’s presentation. The study reinforces findings of her own group in Hispanic and Latinx individuals with MS. Some comorbidities are more common among these groups, which is exacerbated by poor health access.

“We have noted that almost 30% of them also have this comorbidity of hypertension, but what is also observed is that only 7% of them are aware [that they have hypertension],” said Dr. Amezcua, who is an associate professor of neurology at the University of Southern California, Los Angeles.

The findings should prompt further research to understand the impact of systemic racism and neighborhood factors, such as disinvestment in the public and private sectors, underresourced hospitals and clinics, and negative infrastructure. “We need to start discussing the (patient’s) environment so we can better understand the community resources they may have available, as well as create innovative transitional care services. We need to also recognize and accept that structural racism and imbalanced distribution of resources and neighborhoods does restrict educational and economic opportunities, as well as health care access and the safety of these marginalized communities,” said Dr. Amezcua.

Dr. Amezcua has consulted for, received speaking fees from, or served on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono. She has received research support from the Bristol-Myers Squibb Foundation and Biogen Idec. Dr. Orlando has no relevant financial disclosures.

SEATTLE – Multiple sclerosis (MS), sometimes thought of as primarily affecting Whites, is also common among Hispanic and Black people. These populations often have more severe disease, likely driven by socioeconomic factors and health care access, according to a new study that examined neighborhood-level data and disease severity in the United States.

“It has previously been thought that MS is less common among non-European Caucasian White populations, driven partly by the well-known association of incidence with latitude. It is abundantly clear at this point that this idea is not true,” said Christopher Orlando, MD, during a presentation at the 2022 annual meeting of the American Academy of Neurology.

He noted that several U.S. studies with large sample sizes have shown greater disease severity and a higher disability burden among Hispanic and Black patients. “Black patients in particular appear to have a higher incidence of disease and a greater proportion of progressive disease phenotypes,” said Dr. Orlando.

Race and ethnicity are unlikely explanations for this disparity, according to Dr. Orlando. “While much remains to be discovered of the genetic underpinnings of MS, what we do know does not support the idea that minorities would have a predilection to more severe disease. For example, the well-known high-risk allele HLA DRB1*1501 appears to have a lower frequency in African populations, compared with European [populations].”

Instead, evidence suggests that interrelated social causes include access to resources, environmental exposures, and psychosocial stress. “These affect health via a number of pathways including direct physical injury, allostatic load, and access to health care,” said Dr. Orlando.
 

Probing racial and ethnic disparities

Previous studies that corrected for social determinants of health such as socioeconomic and insurance status reduce the association between MS disability and race, but they do not completely explain it.

To get a better understanding of the impacts of these factors, researchers have used neighborhood-level data combined with information on socioeconomic status and social deprivation to identify associations with MS severity.

At the conference, Dr. Orlando presented a new study that is the first to use this methodology in the United States, and it is the first to apply it to the study of racial and ethnic disparities in MS.

The study confirmed more severe disability in Hispanic and Black patients than in White patients. Clinical factors associated with more severe disease were similar across the three groups, with some small differences among individual traits. “More stark differences appeared when we compared social determinants of health. Hispanic patients were less likely to speak English as a primary language or to complete 12 years of education. Black patients were less likely to live in a rural county and more likely to be unemployed. One particularly stark difference was in the number of unemployed specifically due to their MS, with only 1 White patient [1.1%], 7 Hispanic patients [7.8%] and 27 Black patients [31.0%],” said Dr. Orlando.

The researchers found that Black and Hispanic patients tend to live in more vulnerable neighborhoods than White patients. The researchers found no significant association between social vulnerability index (SVI) values and MS severity, though there was an association in a separate analysis that only included White patients. The SVI uses 15 measures taken from the U.S. Census to identify communities that might require additional support during natural disasters.

“It would appear that the sheer complexity both in variety and magnitude of the social determinants of health are such that by far the stronger association is with race and ethnicity, which are surrogates for any number of social determinants and societal inequities,” said Dr. Orlando.
 

What drives the inequity?

Dr. Orlando acknowledged that some might wonder if these results indicate a true biologically intrinsic factor such as genetic predisposition. “I want to warn against that kind of thinking in the strongest possible terms. It is implausible on several levels. It’s not biologically plausible based on our understanding that race and ethnicity are not genetic constructs. And it’s also not numerically plausible based on these data,” said Dr. Orlando.

While some of the drivers of this inequity have been partially examined, many have not been studied. “As long as this is the case, our ability to fulfill our roles as physicians will be limited in several important ways. Our ability to assess our patients’ individual risk will be missing key information, which will limit the efficacy of shared decision-making, which of course is the cornerstone of MS treatment. In addition, we will continue to struggle to include minority patients in our research studies, and the very design and results of those studies may be misguided, as we will either fail to include these populations, or we will fail to adjust for important confounders,” he said.
 

New answers, new questions

The neighborhood-level data examined by Dr. Orlando’s group “brings extra information in terms of the negative impact of social determinants of health. The disparity seen in neighborhood living is quite striking,” said Lilyana Amezcua, MD, who served as a discussant for Dr. Orlando’s presentation. The study reinforces findings of her own group in Hispanic and Latinx individuals with MS. Some comorbidities are more common among these groups, which is exacerbated by poor health access.

“We have noted that almost 30% of them also have this comorbidity of hypertension, but what is also observed is that only 7% of them are aware [that they have hypertension],” said Dr. Amezcua, who is an associate professor of neurology at the University of Southern California, Los Angeles.

The findings should prompt further research to understand the impact of systemic racism and neighborhood factors, such as disinvestment in the public and private sectors, underresourced hospitals and clinics, and negative infrastructure. “We need to start discussing the (patient’s) environment so we can better understand the community resources they may have available, as well as create innovative transitional care services. We need to also recognize and accept that structural racism and imbalanced distribution of resources and neighborhoods does restrict educational and economic opportunities, as well as health care access and the safety of these marginalized communities,” said Dr. Amezcua.

Dr. Amezcua has consulted for, received speaking fees from, or served on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono. She has received research support from the Bristol-Myers Squibb Foundation and Biogen Idec. Dr. Orlando has no relevant financial disclosures.

SEATTLE – Multiple sclerosis (MS), sometimes thought of as primarily affecting Whites, is also common among Hispanic and Black people. These populations often have more severe disease, likely driven by socioeconomic factors and health care access, according to a new study that examined neighborhood-level data and disease severity in the United States.

“It has previously been thought that MS is less common among non-European Caucasian White populations, driven partly by the well-known association of incidence with latitude. It is abundantly clear at this point that this idea is not true,” said Christopher Orlando, MD, during a presentation at the 2022 annual meeting of the American Academy of Neurology.

He noted that several U.S. studies with large sample sizes have shown greater disease severity and a higher disability burden among Hispanic and Black patients. “Black patients in particular appear to have a higher incidence of disease and a greater proportion of progressive disease phenotypes,” said Dr. Orlando.

Race and ethnicity are unlikely explanations for this disparity, according to Dr. Orlando. “While much remains to be discovered of the genetic underpinnings of MS, what we do know does not support the idea that minorities would have a predilection to more severe disease. For example, the well-known high-risk allele HLA DRB1*1501 appears to have a lower frequency in African populations, compared with European [populations].”

Instead, evidence suggests that interrelated social causes include access to resources, environmental exposures, and psychosocial stress. “These affect health via a number of pathways including direct physical injury, allostatic load, and access to health care,” said Dr. Orlando.
 

Probing racial and ethnic disparities

Previous studies that corrected for social determinants of health such as socioeconomic and insurance status reduce the association between MS disability and race, but they do not completely explain it.

To get a better understanding of the impacts of these factors, researchers have used neighborhood-level data combined with information on socioeconomic status and social deprivation to identify associations with MS severity.

At the conference, Dr. Orlando presented a new study that is the first to use this methodology in the United States, and it is the first to apply it to the study of racial and ethnic disparities in MS.

The study confirmed more severe disability in Hispanic and Black patients than in White patients. Clinical factors associated with more severe disease were similar across the three groups, with some small differences among individual traits. “More stark differences appeared when we compared social determinants of health. Hispanic patients were less likely to speak English as a primary language or to complete 12 years of education. Black patients were less likely to live in a rural county and more likely to be unemployed. One particularly stark difference was in the number of unemployed specifically due to their MS, with only 1 White patient [1.1%], 7 Hispanic patients [7.8%] and 27 Black patients [31.0%],” said Dr. Orlando.

The researchers found that Black and Hispanic patients tend to live in more vulnerable neighborhoods than White patients. The researchers found no significant association between social vulnerability index (SVI) values and MS severity, though there was an association in a separate analysis that only included White patients. The SVI uses 15 measures taken from the U.S. Census to identify communities that might require additional support during natural disasters.

“It would appear that the sheer complexity both in variety and magnitude of the social determinants of health are such that by far the stronger association is with race and ethnicity, which are surrogates for any number of social determinants and societal inequities,” said Dr. Orlando.
 

What drives the inequity?

Dr. Orlando acknowledged that some might wonder if these results indicate a true biologically intrinsic factor such as genetic predisposition. “I want to warn against that kind of thinking in the strongest possible terms. It is implausible on several levels. It’s not biologically plausible based on our understanding that race and ethnicity are not genetic constructs. And it’s also not numerically plausible based on these data,” said Dr. Orlando.

While some of the drivers of this inequity have been partially examined, many have not been studied. “As long as this is the case, our ability to fulfill our roles as physicians will be limited in several important ways. Our ability to assess our patients’ individual risk will be missing key information, which will limit the efficacy of shared decision-making, which of course is the cornerstone of MS treatment. In addition, we will continue to struggle to include minority patients in our research studies, and the very design and results of those studies may be misguided, as we will either fail to include these populations, or we will fail to adjust for important confounders,” he said.
 

New answers, new questions

The neighborhood-level data examined by Dr. Orlando’s group “brings extra information in terms of the negative impact of social determinants of health. The disparity seen in neighborhood living is quite striking,” said Lilyana Amezcua, MD, who served as a discussant for Dr. Orlando’s presentation. The study reinforces findings of her own group in Hispanic and Latinx individuals with MS. Some comorbidities are more common among these groups, which is exacerbated by poor health access.

“We have noted that almost 30% of them also have this comorbidity of hypertension, but what is also observed is that only 7% of them are aware [that they have hypertension],” said Dr. Amezcua, who is an associate professor of neurology at the University of Southern California, Los Angeles.

The findings should prompt further research to understand the impact of systemic racism and neighborhood factors, such as disinvestment in the public and private sectors, underresourced hospitals and clinics, and negative infrastructure. “We need to start discussing the (patient’s) environment so we can better understand the community resources they may have available, as well as create innovative transitional care services. We need to also recognize and accept that structural racism and imbalanced distribution of resources and neighborhoods does restrict educational and economic opportunities, as well as health care access and the safety of these marginalized communities,” said Dr. Amezcua.

Dr. Amezcua has consulted for, received speaking fees from, or served on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono. She has received research support from the Bristol-Myers Squibb Foundation and Biogen Idec. Dr. Orlando has no relevant financial disclosures.

A ketogenic diet may reduce disability and improve quality of life, fatigue, and depression in patients with multiple sclerosis (MS), new research suggests.

High-fat, low-carbohydrate ketogenic diets mimic a fasting state and promote a more efficient use of energy – and have previously been shown to affect immune regulation. The diet helps lower blood sugar in individuals with type 2 diabetes and has been used for years to improve seizure control in patients with epilepsy, researchers note.

However, “there is a paucity of literature on the ketogenic diet in MS currently,” said principal investigator J. Nicholas Brenton, MD, University of Virginia, Charlottesville.

“The current study demonstrates the safety, tolerability, and potential clinical benefits of a ketogenic diet over 6 months in patients with relapsing MS,” Dr. Brenton said.

The were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Palatable, beneficial

The open-label, uncontrolled study included 65 patients with relapsing MS who followed a ketogenic diet for 6 months. Investigators monitored adherence by daily urine ketone testing.

Patient-reported fatigue, depression, and quality-of-life scores were obtained at baseline, in addition to fasting adipokines and pertinent MS-related clinical outcome metrics. Baseline study metrics were repeated at 3 and/or 6 months while on the ketogenic diet.

Of the patient group, 83% adhered to the ketogenic diet for the full 6-month study period.

The ketogenic diet was associated with reductions in fat mass from baseline to 6 months (41.3 vs. 32.0 kg; P < .001) and a significant decline in fatigue and depression scores, the investigators reported.

MS quality-of-life physical and mental composite scores also improved while on the ketogenic diet (P < .001 for both).

A significant decrease from baseline to 6 months in Expanded Disability Status Scale scores, signifying improvement, was observed (2.3 vs. 1.9; P < .001).

Improvements were also shown on the 6-minute walk (1,631 vs. 1,733 feet; P < .001) and the nine-hole peg test (21.5 vs. 20.3 seconds; P < .001).

At 6 months on the diet, fasting serum leptin was significantly lower (25.5 vs. 14 ng/mL; P <.001), and adiponectin was higher (11.4 vs. 13.5 μg/mL, P = .002).
 

Justifies further research

The current study builds on an earlier one that Dr. Brenton and colleagues conducted in 2019 that showed that the ketogenic diet was feasible in patients with MS. “Our data justify the need for future studies of ketogenic diets as a complementary therapeutic approach to the treatment of MS,” Dr. Brenton said.

He noted that there may be multiple mechanisms of benefit when considering the ketogenic diet. “One avenue is via reduction in total body fat. This is an important aspect as we continue to learn more about the role of obesity and fat-derived inflammation in MS,” Dr. Brenton said.

“Ketogenic diets also have immunomodulatory properties,” such as the capacity to reduce oxidative damage from metabolic stress, increase mitochondrial biogenesis, and reduce systemic inflammation, he added. “These intrinsic properties of the ketogenic diet make it appealing to study in immune-mediated diseases, such as MS.”

Dr. Brenton cautioned that the data demonstrate the diet’s safety over 6 months but that the study was not designed to assess its long-term implications in MS. “Thus, while our results support the rationale for a larger-scale study of ketogenic diets as a complementary treatment for MS, our data does not support its widespread adoption outside of a clinical trial,” he said.
 

Remarkable adherence

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “variations of the ketogenic diet have been popularized in the general population for weight loss and further studied for other medical conditions [that are] largely immune-related, including MS.”

He noted that it was “remarkable” that the vast majority of study participants with MS adhered to the very regimented ketogenic diet for 6 months.

Seeing this translate into the real world “will be the next milestone, in addition to its impact on relapses and brain lesions as seen on MRI,” which are the classic markers of MS, said Dr. Lakhan, who was not involved with the research.

He cautioned that “even if one can follow the ketogenic diet, certain conditions can be made worse. This includes kidney stones, liver disease, reflux, constipation, and other metabolic disorders.”

The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health and by the ZiMS Foundation. Dr. Brenton and Dr. Lakhan have reported no relevant financial relationships.

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

A ketogenic diet may reduce disability and improve quality of life, fatigue, and depression in patients with multiple sclerosis (MS), new research suggests.

High-fat, low-carbohydrate ketogenic diets mimic a fasting state and promote a more efficient use of energy – and have previously been shown to affect immune regulation. The diet helps lower blood sugar in individuals with type 2 diabetes and has been used for years to improve seizure control in patients with epilepsy, researchers note.

However, “there is a paucity of literature on the ketogenic diet in MS currently,” said principal investigator J. Nicholas Brenton, MD, University of Virginia, Charlottesville.

“The current study demonstrates the safety, tolerability, and potential clinical benefits of a ketogenic diet over 6 months in patients with relapsing MS,” Dr. Brenton said.

The were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Palatable, beneficial

The open-label, uncontrolled study included 65 patients with relapsing MS who followed a ketogenic diet for 6 months. Investigators monitored adherence by daily urine ketone testing.

Patient-reported fatigue, depression, and quality-of-life scores were obtained at baseline, in addition to fasting adipokines and pertinent MS-related clinical outcome metrics. Baseline study metrics were repeated at 3 and/or 6 months while on the ketogenic diet.

Of the patient group, 83% adhered to the ketogenic diet for the full 6-month study period.

The ketogenic diet was associated with reductions in fat mass from baseline to 6 months (41.3 vs. 32.0 kg; P < .001) and a significant decline in fatigue and depression scores, the investigators reported.

MS quality-of-life physical and mental composite scores also improved while on the ketogenic diet (P < .001 for both).

A significant decrease from baseline to 6 months in Expanded Disability Status Scale scores, signifying improvement, was observed (2.3 vs. 1.9; P < .001).

Improvements were also shown on the 6-minute walk (1,631 vs. 1,733 feet; P < .001) and the nine-hole peg test (21.5 vs. 20.3 seconds; P < .001).

At 6 months on the diet, fasting serum leptin was significantly lower (25.5 vs. 14 ng/mL; P <.001), and adiponectin was higher (11.4 vs. 13.5 μg/mL, P = .002).
 

Justifies further research

The current study builds on an earlier one that Dr. Brenton and colleagues conducted in 2019 that showed that the ketogenic diet was feasible in patients with MS. “Our data justify the need for future studies of ketogenic diets as a complementary therapeutic approach to the treatment of MS,” Dr. Brenton said.

He noted that there may be multiple mechanisms of benefit when considering the ketogenic diet. “One avenue is via reduction in total body fat. This is an important aspect as we continue to learn more about the role of obesity and fat-derived inflammation in MS,” Dr. Brenton said.

“Ketogenic diets also have immunomodulatory properties,” such as the capacity to reduce oxidative damage from metabolic stress, increase mitochondrial biogenesis, and reduce systemic inflammation, he added. “These intrinsic properties of the ketogenic diet make it appealing to study in immune-mediated diseases, such as MS.”

Dr. Brenton cautioned that the data demonstrate the diet’s safety over 6 months but that the study was not designed to assess its long-term implications in MS. “Thus, while our results support the rationale for a larger-scale study of ketogenic diets as a complementary treatment for MS, our data does not support its widespread adoption outside of a clinical trial,” he said.
 

Remarkable adherence

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “variations of the ketogenic diet have been popularized in the general population for weight loss and further studied for other medical conditions [that are] largely immune-related, including MS.”

He noted that it was “remarkable” that the vast majority of study participants with MS adhered to the very regimented ketogenic diet for 6 months.

Seeing this translate into the real world “will be the next milestone, in addition to its impact on relapses and brain lesions as seen on MRI,” which are the classic markers of MS, said Dr. Lakhan, who was not involved with the research.

He cautioned that “even if one can follow the ketogenic diet, certain conditions can be made worse. This includes kidney stones, liver disease, reflux, constipation, and other metabolic disorders.”

The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health and by the ZiMS Foundation. Dr. Brenton and Dr. Lakhan have reported no relevant financial relationships.

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

A ketogenic diet may reduce disability and improve quality of life, fatigue, and depression in patients with multiple sclerosis (MS), new research suggests.

High-fat, low-carbohydrate ketogenic diets mimic a fasting state and promote a more efficient use of energy – and have previously been shown to affect immune regulation. The diet helps lower blood sugar in individuals with type 2 diabetes and has been used for years to improve seizure control in patients with epilepsy, researchers note.

However, “there is a paucity of literature on the ketogenic diet in MS currently,” said principal investigator J. Nicholas Brenton, MD, University of Virginia, Charlottesville.

“The current study demonstrates the safety, tolerability, and potential clinical benefits of a ketogenic diet over 6 months in patients with relapsing MS,” Dr. Brenton said.

The were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Palatable, beneficial

The open-label, uncontrolled study included 65 patients with relapsing MS who followed a ketogenic diet for 6 months. Investigators monitored adherence by daily urine ketone testing.

Patient-reported fatigue, depression, and quality-of-life scores were obtained at baseline, in addition to fasting adipokines and pertinent MS-related clinical outcome metrics. Baseline study metrics were repeated at 3 and/or 6 months while on the ketogenic diet.

Of the patient group, 83% adhered to the ketogenic diet for the full 6-month study period.

The ketogenic diet was associated with reductions in fat mass from baseline to 6 months (41.3 vs. 32.0 kg; P < .001) and a significant decline in fatigue and depression scores, the investigators reported.

MS quality-of-life physical and mental composite scores also improved while on the ketogenic diet (P < .001 for both).

A significant decrease from baseline to 6 months in Expanded Disability Status Scale scores, signifying improvement, was observed (2.3 vs. 1.9; P < .001).

Improvements were also shown on the 6-minute walk (1,631 vs. 1,733 feet; P < .001) and the nine-hole peg test (21.5 vs. 20.3 seconds; P < .001).

At 6 months on the diet, fasting serum leptin was significantly lower (25.5 vs. 14 ng/mL; P <.001), and adiponectin was higher (11.4 vs. 13.5 μg/mL, P = .002).
 

Justifies further research

The current study builds on an earlier one that Dr. Brenton and colleagues conducted in 2019 that showed that the ketogenic diet was feasible in patients with MS. “Our data justify the need for future studies of ketogenic diets as a complementary therapeutic approach to the treatment of MS,” Dr. Brenton said.

He noted that there may be multiple mechanisms of benefit when considering the ketogenic diet. “One avenue is via reduction in total body fat. This is an important aspect as we continue to learn more about the role of obesity and fat-derived inflammation in MS,” Dr. Brenton said.

“Ketogenic diets also have immunomodulatory properties,” such as the capacity to reduce oxidative damage from metabolic stress, increase mitochondrial biogenesis, and reduce systemic inflammation, he added. “These intrinsic properties of the ketogenic diet make it appealing to study in immune-mediated diseases, such as MS.”

Dr. Brenton cautioned that the data demonstrate the diet’s safety over 6 months but that the study was not designed to assess its long-term implications in MS. “Thus, while our results support the rationale for a larger-scale study of ketogenic diets as a complementary treatment for MS, our data does not support its widespread adoption outside of a clinical trial,” he said.
 

Remarkable adherence

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “variations of the ketogenic diet have been popularized in the general population for weight loss and further studied for other medical conditions [that are] largely immune-related, including MS.”

He noted that it was “remarkable” that the vast majority of study participants with MS adhered to the very regimented ketogenic diet for 6 months.

Seeing this translate into the real world “will be the next milestone, in addition to its impact on relapses and brain lesions as seen on MRI,” which are the classic markers of MS, said Dr. Lakhan, who was not involved with the research.

He cautioned that “even if one can follow the ketogenic diet, certain conditions can be made worse. This includes kidney stones, liver disease, reflux, constipation, and other metabolic disorders.”

The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health and by the ZiMS Foundation. Dr. Brenton and Dr. Lakhan have reported no relevant financial relationships.

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

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

Received income in an amount equal to or greater than $250 from: Actelion

Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

Received income in an amount equal to or greater than $250 from: Actelion

Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

Received income in an amount equal to or greater than $250 from: Actelion

Key clinical point: Physical activity increased peripheral levels of brain-derived neurotrophic factor (BDNF) in patients with multiple sclerosis (MS).

Major finding: Serum BDNF concentrations were significantly higher after exercise intervention compared with the preintervention levels (standardized mean difference 0.3309; P = .0275).

Study details: This was a meta-analysis of 13 exercise intervention clinical trials involving 271 patients with MS.

Disclosures: The authors did not receive any funding for this work. The authors declared no conflicts of interest.

Source: Shobeiri P et al. Exercise-induced increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: A systematic review and meta-analysis of exercise intervention trials. PLoS One. 2022;17(3):e0264557 (Mar 3). Doi: 10.1371/journal.pone.0264557

Key clinical point: Physical activity increased peripheral levels of brain-derived neurotrophic factor (BDNF) in patients with multiple sclerosis (MS).

Major finding: Serum BDNF concentrations were significantly higher after exercise intervention compared with the preintervention levels (standardized mean difference 0.3309; P = .0275).

Study details: This was a meta-analysis of 13 exercise intervention clinical trials involving 271 patients with MS.

Disclosures: The authors did not receive any funding for this work. The authors declared no conflicts of interest.

Source: Shobeiri P et al. Exercise-induced increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: A systematic review and meta-analysis of exercise intervention trials. PLoS One. 2022;17(3):e0264557 (Mar 3). Doi: 10.1371/journal.pone.0264557

Key clinical point: Physical activity increased peripheral levels of brain-derived neurotrophic factor (BDNF) in patients with multiple sclerosis (MS).

Major finding: Serum BDNF concentrations were significantly higher after exercise intervention compared with the preintervention levels (standardized mean difference 0.3309; P = .0275).

Study details: This was a meta-analysis of 13 exercise intervention clinical trials involving 271 patients with MS.

Disclosures: The authors did not receive any funding for this work. The authors declared no conflicts of interest.

Source: Shobeiri P et al. Exercise-induced increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: A systematic review and meta-analysis of exercise intervention trials. PLoS One. 2022;17(3):e0264557 (Mar 3). Doi: 10.1371/journal.pone.0264557

Key clinical point: At least 13% of cases of multiple sclerosis (MS) can be prevented if tobacco smoking is avoided, indicating the need for integrated programs aimed not only at smoking cessation but also at smoking prevention.

Major finding: The overall attributable fraction (AF) of MS because of smoking was 13.1% (95% CI 10.7%-15.4%), with AF being 0.6% (95% CI 0%-2%) in ex-smokers, indicating the beneficial effects of smoking cessation. Ever-smokers were at a 41% (95% CI 1.33%-1.50%) increased risk for MS than never smokers.

Study details: This was a population-based matched case-control study including 9,419 patients with MS and 9,419 matched control individuals. 

Disclosures: No external funding was received for this study. The authors declared no conflicts of interest.

Source: Manouchehrinia A et al. Smoking attributable risk in multiple sclerosis. Front Immunol. 2022;13:840158 (Mar 3). Doi: 10.3389/fimmu.2022.840158

Key clinical point: At least 13% of cases of multiple sclerosis (MS) can be prevented if tobacco smoking is avoided, indicating the need for integrated programs aimed not only at smoking cessation but also at smoking prevention.

Major finding: The overall attributable fraction (AF) of MS because of smoking was 13.1% (95% CI 10.7%-15.4%), with AF being 0.6% (95% CI 0%-2%) in ex-smokers, indicating the beneficial effects of smoking cessation. Ever-smokers were at a 41% (95% CI 1.33%-1.50%) increased risk for MS than never smokers.

Study details: This was a population-based matched case-control study including 9,419 patients with MS and 9,419 matched control individuals. 

Disclosures: No external funding was received for this study. The authors declared no conflicts of interest.

Source: Manouchehrinia A et al. Smoking attributable risk in multiple sclerosis. Front Immunol. 2022;13:840158 (Mar 3). Doi: 10.3389/fimmu.2022.840158

Key clinical point: At least 13% of cases of multiple sclerosis (MS) can be prevented if tobacco smoking is avoided, indicating the need for integrated programs aimed not only at smoking cessation but also at smoking prevention.

Major finding: The overall attributable fraction (AF) of MS because of smoking was 13.1% (95% CI 10.7%-15.4%), with AF being 0.6% (95% CI 0%-2%) in ex-smokers, indicating the beneficial effects of smoking cessation. Ever-smokers were at a 41% (95% CI 1.33%-1.50%) increased risk for MS than never smokers.

Study details: This was a population-based matched case-control study including 9,419 patients with MS and 9,419 matched control individuals. 

Disclosures: No external funding was received for this study. The authors declared no conflicts of interest.

Source: Manouchehrinia A et al. Smoking attributable risk in multiple sclerosis. Front Immunol. 2022;13:840158 (Mar 3). Doi: 10.3389/fimmu.2022.840158