Multiple Sclerosis Hub

NASHVILLE—The microbiome composition of patients with multiple sclerosis (MS) may differ significantly from that of healthy controls, according to data presented at the 2018 CMSC Annual Meeting.

Although the etiology of MS remains unknown, genetic and environmental factors play a role. Evidence from animal models has suggested that alteration of the gut microbiota may modulate immune-mediated demyelination, suggesting a role of the microbiome in MS pathogenesis.

To examine the gut microbiome in patients with relapsing MS versus controls, Raffaella Umeton, MD, Neurology Resident Physician at the University of Massachusetts Memorial Medical Center in Worcester, and colleagues collected 42 stool samples from patients with relapsing-remitting MS and secondary progressive MS with relapses, as well as 28 control samples from healthy donors.

Investigators obtained demographic and clinical data from medical record review and extracted DNA from stool samples. Their statistical analyses included Quantitative Insights Into Microbial Ecology (QIIME) for comparing operational taxonomic unit representation at the species, genus, and family levels.

Ruminococcus torques, Ruminococcus obeum, and Lactospiraces bacterium showed a significantly higher abundance in the relapsing-remitting MS population, compared with healthy controls, and these associations were confirmed at the genus level. Associations with Escherichia coli and Oscillibacter also were significant and confirmed at the genus and family levels.

Bacteroides fragilis and Roseburia were more abundant in healthy donors than in patients with relapsing-remitting MS, and Haemophilus parainfluenzae and Sutterella wadsworthensis were more abundant in healthy donors at the species, genus, and family levels.

“Larger studies are necessary to investigate the changes within the gut microbiome and MS, which may lead to potential disease activity biomarkers and therapies,” Dr. Umeton and colleagues concluded. 

—Erica Tricarico

NASHVILLE—The microbiome composition of patients with multiple sclerosis (MS) may differ significantly from that of healthy controls, according to data presented at the 2018 CMSC Annual Meeting.

Although the etiology of MS remains unknown, genetic and environmental factors play a role. Evidence from animal models has suggested that alteration of the gut microbiota may modulate immune-mediated demyelination, suggesting a role of the microbiome in MS pathogenesis.

To examine the gut microbiome in patients with relapsing MS versus controls, Raffaella Umeton, MD, Neurology Resident Physician at the University of Massachusetts Memorial Medical Center in Worcester, and colleagues collected 42 stool samples from patients with relapsing-remitting MS and secondary progressive MS with relapses, as well as 28 control samples from healthy donors.

Investigators obtained demographic and clinical data from medical record review and extracted DNA from stool samples. Their statistical analyses included Quantitative Insights Into Microbial Ecology (QIIME) for comparing operational taxonomic unit representation at the species, genus, and family levels.

Ruminococcus torques, Ruminococcus obeum, and Lactospiraces bacterium showed a significantly higher abundance in the relapsing-remitting MS population, compared with healthy controls, and these associations were confirmed at the genus level. Associations with Escherichia coli and Oscillibacter also were significant and confirmed at the genus and family levels.

Bacteroides fragilis and Roseburia were more abundant in healthy donors than in patients with relapsing-remitting MS, and Haemophilus parainfluenzae and Sutterella wadsworthensis were more abundant in healthy donors at the species, genus, and family levels.

“Larger studies are necessary to investigate the changes within the gut microbiome and MS, which may lead to potential disease activity biomarkers and therapies,” Dr. Umeton and colleagues concluded. 

—Erica Tricarico

NASHVILLE—The microbiome composition of patients with multiple sclerosis (MS) may differ significantly from that of healthy controls, according to data presented at the 2018 CMSC Annual Meeting.

Although the etiology of MS remains unknown, genetic and environmental factors play a role. Evidence from animal models has suggested that alteration of the gut microbiota may modulate immune-mediated demyelination, suggesting a role of the microbiome in MS pathogenesis.

To examine the gut microbiome in patients with relapsing MS versus controls, Raffaella Umeton, MD, Neurology Resident Physician at the University of Massachusetts Memorial Medical Center in Worcester, and colleagues collected 42 stool samples from patients with relapsing-remitting MS and secondary progressive MS with relapses, as well as 28 control samples from healthy donors.

Investigators obtained demographic and clinical data from medical record review and extracted DNA from stool samples. Their statistical analyses included Quantitative Insights Into Microbial Ecology (QIIME) for comparing operational taxonomic unit representation at the species, genus, and family levels.

Ruminococcus torques, Ruminococcus obeum, and Lactospiraces bacterium showed a significantly higher abundance in the relapsing-remitting MS population, compared with healthy controls, and these associations were confirmed at the genus level. Associations with Escherichia coli and Oscillibacter also were significant and confirmed at the genus and family levels.

Bacteroides fragilis and Roseburia were more abundant in healthy donors than in patients with relapsing-remitting MS, and Haemophilus parainfluenzae and Sutterella wadsworthensis were more abundant in healthy donors at the species, genus, and family levels.

“Larger studies are necessary to investigate the changes within the gut microbiome and MS, which may lead to potential disease activity biomarkers and therapies,” Dr. Umeton and colleagues concluded. 

—Erica Tricarico

NASHVILLE—Adherence to a Mediterranean-style diet may be associated with less severe depressive and cognitive impairment symptoms among patients with multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting.

Symptoms of depression, fatigue, and cognitive impairment are common among people with MS and adversely affect quality of life. In the general population, adherence to a Mediterranean-style diet has been associated with improvements in mood, fatigue, and cognitive impairment. It unknown, however, if similar associations exist in the MS population.

To study this question, Leah Mische, a medical student at the Johns Hopkins University School of Medicine in Baltimore, and colleagues assessed the associations between adherence to a Mediterranean-style diet and self-reported symptoms of depression, fatigue, and cognitive impairment in patients with MS.

Thirty-four patients with MS completed a 24-hour dietary recall. Researchers used the responses to quantify patients’ adherence to a Mediterranean-style diet using a validated scoring approach that incorporates high intakes of fruits, vegetables, whole grains, seafood, polyunsaturated fat, and nuts and legumes, low intakes of red and processed meats, and moderate alcohol consumption.

Patients with a greater than median intake of each food group received 1 point. Scores for red and processed meats (where lower intakes are desired) were reversed, and those with moderate alcohol consumption also received 1 point.

The investigators obtained overall Mediterranean diet scores, which ranged from 0 (poor diet quality) to 8 (high diet quality), by summing up individual food group points. In addition, participants provided information about depression, fatigue, and cognitive impairment symptoms by completing Neuro-Quality of Life subscales. Finally, the researchers assessed the association between Mediterranean diet scores and Neuro-Quality of Life subscales using Spearman correlations and linear regression models adjusted for age and sex.

The mean age of participants was 44.6, and 67% were female. Higher Mediterranean diet scores were associated with less severe depressive and cognitive impairment symptoms. In addition, patients in the top tertile of Mediterranean diet scores had  a significantly lower average depressive symptoms score, compared with those in the bottom tertile (mean difference, 4.1). Mediterranean diet scores were not associated with fatigue severity.

“Interventional studies are needed to determine the directionality of this relationship,” Ms. Mische and colleagues concluded.

—Erica Tricarico

NASHVILLE—Adherence to a Mediterranean-style diet may be associated with less severe depressive and cognitive impairment symptoms among patients with multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting.

Symptoms of depression, fatigue, and cognitive impairment are common among people with MS and adversely affect quality of life. In the general population, adherence to a Mediterranean-style diet has been associated with improvements in mood, fatigue, and cognitive impairment. It unknown, however, if similar associations exist in the MS population.

To study this question, Leah Mische, a medical student at the Johns Hopkins University School of Medicine in Baltimore, and colleagues assessed the associations between adherence to a Mediterranean-style diet and self-reported symptoms of depression, fatigue, and cognitive impairment in patients with MS.

Thirty-four patients with MS completed a 24-hour dietary recall. Researchers used the responses to quantify patients’ adherence to a Mediterranean-style diet using a validated scoring approach that incorporates high intakes of fruits, vegetables, whole grains, seafood, polyunsaturated fat, and nuts and legumes, low intakes of red and processed meats, and moderate alcohol consumption.

Patients with a greater than median intake of each food group received 1 point. Scores for red and processed meats (where lower intakes are desired) were reversed, and those with moderate alcohol consumption also received 1 point.

The investigators obtained overall Mediterranean diet scores, which ranged from 0 (poor diet quality) to 8 (high diet quality), by summing up individual food group points. In addition, participants provided information about depression, fatigue, and cognitive impairment symptoms by completing Neuro-Quality of Life subscales. Finally, the researchers assessed the association between Mediterranean diet scores and Neuro-Quality of Life subscales using Spearman correlations and linear regression models adjusted for age and sex.

The mean age of participants was 44.6, and 67% were female. Higher Mediterranean diet scores were associated with less severe depressive and cognitive impairment symptoms. In addition, patients in the top tertile of Mediterranean diet scores had  a significantly lower average depressive symptoms score, compared with those in the bottom tertile (mean difference, 4.1). Mediterranean diet scores were not associated with fatigue severity.

“Interventional studies are needed to determine the directionality of this relationship,” Ms. Mische and colleagues concluded.

—Erica Tricarico

NASHVILLE—Adherence to a Mediterranean-style diet may be associated with less severe depressive and cognitive impairment symptoms among patients with multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting.

Symptoms of depression, fatigue, and cognitive impairment are common among people with MS and adversely affect quality of life. In the general population, adherence to a Mediterranean-style diet has been associated with improvements in mood, fatigue, and cognitive impairment. It unknown, however, if similar associations exist in the MS population.

To study this question, Leah Mische, a medical student at the Johns Hopkins University School of Medicine in Baltimore, and colleagues assessed the associations between adherence to a Mediterranean-style diet and self-reported symptoms of depression, fatigue, and cognitive impairment in patients with MS.

Thirty-four patients with MS completed a 24-hour dietary recall. Researchers used the responses to quantify patients’ adherence to a Mediterranean-style diet using a validated scoring approach that incorporates high intakes of fruits, vegetables, whole grains, seafood, polyunsaturated fat, and nuts and legumes, low intakes of red and processed meats, and moderate alcohol consumption.

Patients with a greater than median intake of each food group received 1 point. Scores for red and processed meats (where lower intakes are desired) were reversed, and those with moderate alcohol consumption also received 1 point.

The investigators obtained overall Mediterranean diet scores, which ranged from 0 (poor diet quality) to 8 (high diet quality), by summing up individual food group points. In addition, participants provided information about depression, fatigue, and cognitive impairment symptoms by completing Neuro-Quality of Life subscales. Finally, the researchers assessed the association between Mediterranean diet scores and Neuro-Quality of Life subscales using Spearman correlations and linear regression models adjusted for age and sex.

The mean age of participants was 44.6, and 67% were female. Higher Mediterranean diet scores were associated with less severe depressive and cognitive impairment symptoms. In addition, patients in the top tertile of Mediterranean diet scores had  a significantly lower average depressive symptoms score, compared with those in the bottom tertile (mean difference, 4.1). Mediterranean diet scores were not associated with fatigue severity.

“Interventional studies are needed to determine the directionality of this relationship,” Ms. Mische and colleagues concluded.

—Erica Tricarico

NASHVILLE—Patients with multiple sclerosis (MS) and 10 or more oligoclonal bands (OCBs) in CSF may have significantly more clinical and radiographic relapses and clinical progression during short-term follow-up than those who have fewer OCBs, according to data described at the 2018 CMSC Annual Meeting. OCBs may have greater diagnostic weight in the future, and their quantity may be important to consider during the selection of disease-modifying therapies, said the investigators.

Data Suggest the Predictive Value of OCBs

OCBs in the CSF are a common laboratory abnormality in MS. More than 90% of patients with MS have this finding. Previous research has suggested that OCBs predict the likelihood of progressing from clinically isolated syndrome to clinically definite MS. When observed early in the disease course, OCBs indicate a worse prognosis. Reflecting this emerging research, the latest version of the McDonald Criteria for MS diagnosis has incorporated OCBs.

Yet the predictive value of OCBs has been incompletely explored, said Christopher Perrone, MD, a resident at the University of Pennsylvania in Philadelphia, and colleagues. “While most studies examine the presence or absence of OCBs with regard to prognosis, only a few small studies have investigated correlations between the number of OCBs on single disease metrics,” he added.

OCBs May Predict Need for Assistive Devices

In their retrospective study, Dr. Perrone and colleagues intended to examine relationships between the number of OCBs and markers of clinical and radiographic relapses and progression in two-year follow-up. They screened 1,270 patients receiving MS disease-modifying therapies for OCB testing. Further selection criteria included a diagnosis of relapsing-remitting MS and adherence to a DMT with two years of follow-up clinical visits and imaging. In all, 128 patients met the inclusion criteria.

The study’s primary outcome measures were clinical relapses (defined as the number of steroid prescriptions) and radiographic relapses (defined as the number of new lesions on MRI) at two-year follow-up. Secondary outcome measures were clinical progression (categorized as independent, cane, walker, or wheelchair) and radiographic progression (net changes in third ventricular width, lateral ventricular width, and cortical width). Unpaired, two-tailed t tests were used for comparative analyses.

At two years, the number of clinical relapses was significantly greater in patients with 10 or more OCBs, compared with patients with fewer than 10 OCBs. Similarly, patients with 10 or more OCBs were more likely to have radiographic relapses, with nearly twice the number of new lesions on MRI at two years, compared with patients with fewer than 10 OCBs. Although the investigators found no significant difference between groups at baseline in the use of an assistive device, within-subjects analysis demonstrated that the use of a new assistive device was more common for patients with 10 or more OCBs. While lateral ventricular width increased more in patients with 10 or more OCBs, changes in third ventricular width and cortical width were not significantly different between groups.

NASHVILLE—Patients with multiple sclerosis (MS) and 10 or more oligoclonal bands (OCBs) in CSF may have significantly more clinical and radiographic relapses and clinical progression during short-term follow-up than those who have fewer OCBs, according to data described at the 2018 CMSC Annual Meeting. OCBs may have greater diagnostic weight in the future, and their quantity may be important to consider during the selection of disease-modifying therapies, said the investigators.

Data Suggest the Predictive Value of OCBs

OCBs in the CSF are a common laboratory abnormality in MS. More than 90% of patients with MS have this finding. Previous research has suggested that OCBs predict the likelihood of progressing from clinically isolated syndrome to clinically definite MS. When observed early in the disease course, OCBs indicate a worse prognosis. Reflecting this emerging research, the latest version of the McDonald Criteria for MS diagnosis has incorporated OCBs.

Yet the predictive value of OCBs has been incompletely explored, said Christopher Perrone, MD, a resident at the University of Pennsylvania in Philadelphia, and colleagues. “While most studies examine the presence or absence of OCBs with regard to prognosis, only a few small studies have investigated correlations between the number of OCBs on single disease metrics,” he added.

OCBs May Predict Need for Assistive Devices

In their retrospective study, Dr. Perrone and colleagues intended to examine relationships between the number of OCBs and markers of clinical and radiographic relapses and progression in two-year follow-up. They screened 1,270 patients receiving MS disease-modifying therapies for OCB testing. Further selection criteria included a diagnosis of relapsing-remitting MS and adherence to a DMT with two years of follow-up clinical visits and imaging. In all, 128 patients met the inclusion criteria.

The study’s primary outcome measures were clinical relapses (defined as the number of steroid prescriptions) and radiographic relapses (defined as the number of new lesions on MRI) at two-year follow-up. Secondary outcome measures were clinical progression (categorized as independent, cane, walker, or wheelchair) and radiographic progression (net changes in third ventricular width, lateral ventricular width, and cortical width). Unpaired, two-tailed t tests were used for comparative analyses.

At two years, the number of clinical relapses was significantly greater in patients with 10 or more OCBs, compared with patients with fewer than 10 OCBs. Similarly, patients with 10 or more OCBs were more likely to have radiographic relapses, with nearly twice the number of new lesions on MRI at two years, compared with patients with fewer than 10 OCBs. Although the investigators found no significant difference between groups at baseline in the use of an assistive device, within-subjects analysis demonstrated that the use of a new assistive device was more common for patients with 10 or more OCBs. While lateral ventricular width increased more in patients with 10 or more OCBs, changes in third ventricular width and cortical width were not significantly different between groups.

NASHVILLE—Patients with multiple sclerosis (MS) and 10 or more oligoclonal bands (OCBs) in CSF may have significantly more clinical and radiographic relapses and clinical progression during short-term follow-up than those who have fewer OCBs, according to data described at the 2018 CMSC Annual Meeting. OCBs may have greater diagnostic weight in the future, and their quantity may be important to consider during the selection of disease-modifying therapies, said the investigators.

Data Suggest the Predictive Value of OCBs

OCBs in the CSF are a common laboratory abnormality in MS. More than 90% of patients with MS have this finding. Previous research has suggested that OCBs predict the likelihood of progressing from clinically isolated syndrome to clinically definite MS. When observed early in the disease course, OCBs indicate a worse prognosis. Reflecting this emerging research, the latest version of the McDonald Criteria for MS diagnosis has incorporated OCBs.

Yet the predictive value of OCBs has been incompletely explored, said Christopher Perrone, MD, a resident at the University of Pennsylvania in Philadelphia, and colleagues. “While most studies examine the presence or absence of OCBs with regard to prognosis, only a few small studies have investigated correlations between the number of OCBs on single disease metrics,” he added.

OCBs May Predict Need for Assistive Devices

In their retrospective study, Dr. Perrone and colleagues intended to examine relationships between the number of OCBs and markers of clinical and radiographic relapses and progression in two-year follow-up. They screened 1,270 patients receiving MS disease-modifying therapies for OCB testing. Further selection criteria included a diagnosis of relapsing-remitting MS and adherence to a DMT with two years of follow-up clinical visits and imaging. In all, 128 patients met the inclusion criteria.

The study’s primary outcome measures were clinical relapses (defined as the number of steroid prescriptions) and radiographic relapses (defined as the number of new lesions on MRI) at two-year follow-up. Secondary outcome measures were clinical progression (categorized as independent, cane, walker, or wheelchair) and radiographic progression (net changes in third ventricular width, lateral ventricular width, and cortical width). Unpaired, two-tailed t tests were used for comparative analyses.

At two years, the number of clinical relapses was significantly greater in patients with 10 or more OCBs, compared with patients with fewer than 10 OCBs. Similarly, patients with 10 or more OCBs were more likely to have radiographic relapses, with nearly twice the number of new lesions on MRI at two years, compared with patients with fewer than 10 OCBs. Although the investigators found no significant difference between groups at baseline in the use of an assistive device, within-subjects analysis demonstrated that the use of a new assistive device was more common for patients with 10 or more OCBs. While lateral ventricular width increased more in patients with 10 or more OCBs, changes in third ventricular width and cortical width were not significantly different between groups.

NASHVILLE—A rapid foot-tapping task can distinguish between healthy controls and people with multiple sclerosis (MS), as well as between MS subtypes, according to a study presented at the 2018 CMSC Annual Meeting. “The associations between foot-tap speed and mobility measures such as the Timed Up and Go [TUG] test and the 25-Foot Walk test [25FWT] suggest that rapid foot tapping may be a useful marker for tracking or predicting progression of mobility dysfunction in people with MS, regardless of their ability to ambulate,” said Sumire Sato, a graduate student in the Neuroscience and Behavior Program at the University of Massachusetts Amherst, and colleagues.

The TUG test and the 25FWT are common clinical measurements that require ambulation and are used to assess mobility in people with MS. Not all people with MS are ambulatory, however. Preliminary, unpublished work by Ms. Sato and colleagues suggests that while the TUG test and the 25FWT can distinguish individuals with MS from controls without MS, they cannot distinguish between nonprogressive (MS-NP) and progressive (MS-P) MS subtypes. “Therefore, there is a critical need to identify a sensitive and nonambulatory task that can distinguish MS subtypes,” said the investigators.

Ms. Sato and colleagues recruited 30 participants with MS-NP, 30 participants with MS-P, and 17 age- and sex-matched controls for a study to determine whether rapid foot tapping ability can distinguish people with MS from controls and between MS subtypes. Each participant wore inertial sensors (manufactured by APDM) on the foot to measure angular velocity and acceleration. Participants were instructed to tap one foot as fast as possible for 10 seconds. Participants performed three trials on each foot while seated with self-selected knee and ankle angle.

The researchers analyzed sensor data using a custom MATLAB program that identified taps as acceleration peaks that occurred after every other zero-crossing of angular velocity. They administered the TUG test and 25FWT to participants to compare mobility to rapid foot tapping. Analysis of variance was used to analyze main effects of group and to make pairwise comparisons between groups. Ms. Sato and colleagues evaluated associations between foot tap count and mobility measures in MS groups using Spearman’s rho.

The researchers observed a main effect of group for foot-tap count, such that tap count differed between controls and participants with MS-NP and MS-P. The tap count also differed between participants with MS-NP and those with MS-P. Foot-tap count was negatively correlated with the 25FWT and the TUG test, thus indicating an association between the slowing of tapping speed and mobility measures.

NASHVILLE—A rapid foot-tapping task can distinguish between healthy controls and people with multiple sclerosis (MS), as well as between MS subtypes, according to a study presented at the 2018 CMSC Annual Meeting. “The associations between foot-tap speed and mobility measures such as the Timed Up and Go [TUG] test and the 25-Foot Walk test [25FWT] suggest that rapid foot tapping may be a useful marker for tracking or predicting progression of mobility dysfunction in people with MS, regardless of their ability to ambulate,” said Sumire Sato, a graduate student in the Neuroscience and Behavior Program at the University of Massachusetts Amherst, and colleagues.

The TUG test and the 25FWT are common clinical measurements that require ambulation and are used to assess mobility in people with MS. Not all people with MS are ambulatory, however. Preliminary, unpublished work by Ms. Sato and colleagues suggests that while the TUG test and the 25FWT can distinguish individuals with MS from controls without MS, they cannot distinguish between nonprogressive (MS-NP) and progressive (MS-P) MS subtypes. “Therefore, there is a critical need to identify a sensitive and nonambulatory task that can distinguish MS subtypes,” said the investigators.

Ms. Sato and colleagues recruited 30 participants with MS-NP, 30 participants with MS-P, and 17 age- and sex-matched controls for a study to determine whether rapid foot tapping ability can distinguish people with MS from controls and between MS subtypes. Each participant wore inertial sensors (manufactured by APDM) on the foot to measure angular velocity and acceleration. Participants were instructed to tap one foot as fast as possible for 10 seconds. Participants performed three trials on each foot while seated with self-selected knee and ankle angle.

The researchers analyzed sensor data using a custom MATLAB program that identified taps as acceleration peaks that occurred after every other zero-crossing of angular velocity. They administered the TUG test and 25FWT to participants to compare mobility to rapid foot tapping. Analysis of variance was used to analyze main effects of group and to make pairwise comparisons between groups. Ms. Sato and colleagues evaluated associations between foot tap count and mobility measures in MS groups using Spearman’s rho.

The researchers observed a main effect of group for foot-tap count, such that tap count differed between controls and participants with MS-NP and MS-P. The tap count also differed between participants with MS-NP and those with MS-P. Foot-tap count was negatively correlated with the 25FWT and the TUG test, thus indicating an association between the slowing of tapping speed and mobility measures.

NASHVILLE—A rapid foot-tapping task can distinguish between healthy controls and people with multiple sclerosis (MS), as well as between MS subtypes, according to a study presented at the 2018 CMSC Annual Meeting. “The associations between foot-tap speed and mobility measures such as the Timed Up and Go [TUG] test and the 25-Foot Walk test [25FWT] suggest that rapid foot tapping may be a useful marker for tracking or predicting progression of mobility dysfunction in people with MS, regardless of their ability to ambulate,” said Sumire Sato, a graduate student in the Neuroscience and Behavior Program at the University of Massachusetts Amherst, and colleagues.

The TUG test and the 25FWT are common clinical measurements that require ambulation and are used to assess mobility in people with MS. Not all people with MS are ambulatory, however. Preliminary, unpublished work by Ms. Sato and colleagues suggests that while the TUG test and the 25FWT can distinguish individuals with MS from controls without MS, they cannot distinguish between nonprogressive (MS-NP) and progressive (MS-P) MS subtypes. “Therefore, there is a critical need to identify a sensitive and nonambulatory task that can distinguish MS subtypes,” said the investigators.

Ms. Sato and colleagues recruited 30 participants with MS-NP, 30 participants with MS-P, and 17 age- and sex-matched controls for a study to determine whether rapid foot tapping ability can distinguish people with MS from controls and between MS subtypes. Each participant wore inertial sensors (manufactured by APDM) on the foot to measure angular velocity and acceleration. Participants were instructed to tap one foot as fast as possible for 10 seconds. Participants performed three trials on each foot while seated with self-selected knee and ankle angle.

The researchers analyzed sensor data using a custom MATLAB program that identified taps as acceleration peaks that occurred after every other zero-crossing of angular velocity. They administered the TUG test and 25FWT to participants to compare mobility to rapid foot tapping. Analysis of variance was used to analyze main effects of group and to make pairwise comparisons between groups. Ms. Sato and colleagues evaluated associations between foot tap count and mobility measures in MS groups using Spearman’s rho.

The researchers observed a main effect of group for foot-tap count, such that tap count differed between controls and participants with MS-NP and MS-P. The tap count also differed between participants with MS-NP and those with MS-P. Foot-tap count was negatively correlated with the 25FWT and the TUG test, thus indicating an association between the slowing of tapping speed and mobility measures.

LOS ANGELES – Patients with multiple sclerosis in the CARE-MS II study who switched from interferon beta-1a therapy to the humanized monoclonal antibody alemtuzumab experienced continued reductions in brain volume loss and lesions on MRI through 5 years, according to follow-up data from the CARE-MS II extension study known as TOPAZ.

These outcomes support core findings from the CARE-MS II study, and suggest that alemtuzumab (Lemtrada) provides a unique treatment approach for patients with prior subcutaneous interferon beta-1a (IFNB-1a) treatment, Daniel Pelletier, MD, reported in a poster discussion session at the annual meeting of the American Academy of Neurology.

In CARE-MS II, relapsing-remitting multiple sclerosis patients with inadequate response to prior therapy experienced improvements in MRI lesions and brain volume loss with two courses of alemtuzumab versus IFNB-1a through 2 years, and in a 4-year extension in which participants discontinued subcutaneous IFNB-1a and initiated alemtuzumab at 12 mg/day, they experienced durable efficacy in the absence of continuous treatment, explained Dr. Pelletier, a professor of neurology at the University of Southern California, Los Angeles.

In the extension, patients could receive alemtuzumab retreatment as needed for relapse/MRI activity or receive other disease-modifying therapies at the investigator’s discretion. Patients completing the extension could enter the 5-year TOPAZ study for further evaluation, he said.

Of 119 patients who completed TOPAZ year 1, and thus had 5 years of follow-up after initiating alemtuzumab, 78% were free of new, gadolinium-enhancing lesions in IFNB-1a year 2; this increased significantly to 92% in post-alemtuzumab year 2, and remained high at 85%-89% in years 3-5. Additionally, 48% of patients were free of new/enlarging T2 lesions in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2 and remained high in years 3-5.

Further, 47% of the TOPAZ patients were MRI disease activity–free in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2, and remained high at 67%-72% in years 3-5.

[email protected]

SOURCE: Pelletier D et al. Neurology. 2018 Apr 10. 90(15 Suppl.):P5.031.

LOS ANGELES – Patients with multiple sclerosis in the CARE-MS II study who switched from interferon beta-1a therapy to the humanized monoclonal antibody alemtuzumab experienced continued reductions in brain volume loss and lesions on MRI through 5 years, according to follow-up data from the CARE-MS II extension study known as TOPAZ.

These outcomes support core findings from the CARE-MS II study, and suggest that alemtuzumab (Lemtrada) provides a unique treatment approach for patients with prior subcutaneous interferon beta-1a (IFNB-1a) treatment, Daniel Pelletier, MD, reported in a poster discussion session at the annual meeting of the American Academy of Neurology.

In CARE-MS II, relapsing-remitting multiple sclerosis patients with inadequate response to prior therapy experienced improvements in MRI lesions and brain volume loss with two courses of alemtuzumab versus IFNB-1a through 2 years, and in a 4-year extension in which participants discontinued subcutaneous IFNB-1a and initiated alemtuzumab at 12 mg/day, they experienced durable efficacy in the absence of continuous treatment, explained Dr. Pelletier, a professor of neurology at the University of Southern California, Los Angeles.

In the extension, patients could receive alemtuzumab retreatment as needed for relapse/MRI activity or receive other disease-modifying therapies at the investigator’s discretion. Patients completing the extension could enter the 5-year TOPAZ study for further evaluation, he said.

Of 119 patients who completed TOPAZ year 1, and thus had 5 years of follow-up after initiating alemtuzumab, 78% were free of new, gadolinium-enhancing lesions in IFNB-1a year 2; this increased significantly to 92% in post-alemtuzumab year 2, and remained high at 85%-89% in years 3-5. Additionally, 48% of patients were free of new/enlarging T2 lesions in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2 and remained high in years 3-5.

Further, 47% of the TOPAZ patients were MRI disease activity–free in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2, and remained high at 67%-72% in years 3-5.

[email protected]

SOURCE: Pelletier D et al. Neurology. 2018 Apr 10. 90(15 Suppl.):P5.031.

LOS ANGELES – Patients with multiple sclerosis in the CARE-MS II study who switched from interferon beta-1a therapy to the humanized monoclonal antibody alemtuzumab experienced continued reductions in brain volume loss and lesions on MRI through 5 years, according to follow-up data from the CARE-MS II extension study known as TOPAZ.

These outcomes support core findings from the CARE-MS II study, and suggest that alemtuzumab (Lemtrada) provides a unique treatment approach for patients with prior subcutaneous interferon beta-1a (IFNB-1a) treatment, Daniel Pelletier, MD, reported in a poster discussion session at the annual meeting of the American Academy of Neurology.

In CARE-MS II, relapsing-remitting multiple sclerosis patients with inadequate response to prior therapy experienced improvements in MRI lesions and brain volume loss with two courses of alemtuzumab versus IFNB-1a through 2 years, and in a 4-year extension in which participants discontinued subcutaneous IFNB-1a and initiated alemtuzumab at 12 mg/day, they experienced durable efficacy in the absence of continuous treatment, explained Dr. Pelletier, a professor of neurology at the University of Southern California, Los Angeles.

In the extension, patients could receive alemtuzumab retreatment as needed for relapse/MRI activity or receive other disease-modifying therapies at the investigator’s discretion. Patients completing the extension could enter the 5-year TOPAZ study for further evaluation, he said.

Of 119 patients who completed TOPAZ year 1, and thus had 5 years of follow-up after initiating alemtuzumab, 78% were free of new, gadolinium-enhancing lesions in IFNB-1a year 2; this increased significantly to 92% in post-alemtuzumab year 2, and remained high at 85%-89% in years 3-5. Additionally, 48% of patients were free of new/enlarging T2 lesions in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2 and remained high in years 3-5.

Further, 47% of the TOPAZ patients were MRI disease activity–free in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2, and remained high at 67%-72% in years 3-5.

[email protected]

SOURCE: Pelletier D et al. Neurology. 2018 Apr 10. 90(15 Suppl.):P5.031.

NASHVILLE, TENN. – Physical activity appears to have profound rehabilitative effects – both physical and cognitive – upon patients with multiple sclerosis, but the body of evidence remains largely based on small, sometimes problematic studies, Alan Thompson, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers.

There are compelling animal data that exercise promotes a number of beneficial neuronal changes that improve patient-reported outcomes, said Dr. Thompson, the Garfield Weston Professor of Clinical Neurology and Neurorehabilitation at University College London (England).

“A lot of animal work suggests that exercise can have a major impact on repair and recovery in neurons, synaptic signaling, dendritic branching, long-term potentiation,” and can beneficially affect inflammation and demyelination, he said. Besides the direct effect on nerves, exercise builds up muscle mass, strengthens connective tissue, improves movement, and reduces cardiovascular risk. “Exercise improves inactivity, but also may improve the underlying disease process,” he said. “The effect can be quite profound, and we are building a very good evidence base to support the use of exercise in MS.”

Unfortunately, the existing body of literature remains unimpressive, Dr. Thompson admitted. He compared research in physical activity to that of medicinal therapeutics. Disease-modifying therapeutics research is highly regulated, very well funded, adequately powered and replicated, and – once it shows positive results – receives substantial marketing and sales effort. “As a result, there can be a substantial impact on care.”

Research on rehabilitation and symptom management, with physical activity and other similar interventions, is not well funded, relies on diverse outcome measures, has small cohort numbers, and often is unreplicated. Even positive results “are just left to lie there,” he said. “Thus, it has a modest impact on care. I would like to see equal resources for both research areas.”

The recent surge in stroke rehabilitation is an excellent example of how academic focus can change practice for neurologic illness, he said. A 2017 research letter in Lancet Neurology described the current state of research on exercise in MS (Lancet Neurol. 2017;16[10];848-56). An accompanying editorial compared the MS literature to that in stroke (Lancet Neurol. 2017;16[10]:768-9).

During 1990-2005, there were almost no clinical studies in rehabilitation for stroke, Parkinson’s disease, spinal cord injury, and MS. Around 2005, things began to change in stroke, with close to 60 publications in just 1 year. During 2010-2015, the pace of research accelerated dramatically. Researchers, clinicians, and patients began to see the immediate and long-term benefits of early poststroke rehabilitation. These interventions have now been encoded in practice guidelines and are a core part of clinical care, Dr. Thompson said.

[email protected]

NASHVILLE, TENN. – Physical activity appears to have profound rehabilitative effects – both physical and cognitive – upon patients with multiple sclerosis, but the body of evidence remains largely based on small, sometimes problematic studies, Alan Thompson, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers.

There are compelling animal data that exercise promotes a number of beneficial neuronal changes that improve patient-reported outcomes, said Dr. Thompson, the Garfield Weston Professor of Clinical Neurology and Neurorehabilitation at University College London (England).

“A lot of animal work suggests that exercise can have a major impact on repair and recovery in neurons, synaptic signaling, dendritic branching, long-term potentiation,” and can beneficially affect inflammation and demyelination, he said. Besides the direct effect on nerves, exercise builds up muscle mass, strengthens connective tissue, improves movement, and reduces cardiovascular risk. “Exercise improves inactivity, but also may improve the underlying disease process,” he said. “The effect can be quite profound, and we are building a very good evidence base to support the use of exercise in MS.”

Unfortunately, the existing body of literature remains unimpressive, Dr. Thompson admitted. He compared research in physical activity to that of medicinal therapeutics. Disease-modifying therapeutics research is highly regulated, very well funded, adequately powered and replicated, and – once it shows positive results – receives substantial marketing and sales effort. “As a result, there can be a substantial impact on care.”

Research on rehabilitation and symptom management, with physical activity and other similar interventions, is not well funded, relies on diverse outcome measures, has small cohort numbers, and often is unreplicated. Even positive results “are just left to lie there,” he said. “Thus, it has a modest impact on care. I would like to see equal resources for both research areas.”

The recent surge in stroke rehabilitation is an excellent example of how academic focus can change practice for neurologic illness, he said. A 2017 research letter in Lancet Neurology described the current state of research on exercise in MS (Lancet Neurol. 2017;16[10];848-56). An accompanying editorial compared the MS literature to that in stroke (Lancet Neurol. 2017;16[10]:768-9).

During 1990-2005, there were almost no clinical studies in rehabilitation for stroke, Parkinson’s disease, spinal cord injury, and MS. Around 2005, things began to change in stroke, with close to 60 publications in just 1 year. During 2010-2015, the pace of research accelerated dramatically. Researchers, clinicians, and patients began to see the immediate and long-term benefits of early poststroke rehabilitation. These interventions have now been encoded in practice guidelines and are a core part of clinical care, Dr. Thompson said.

[email protected]

NASHVILLE, TENN. – Physical activity appears to have profound rehabilitative effects – both physical and cognitive – upon patients with multiple sclerosis, but the body of evidence remains largely based on small, sometimes problematic studies, Alan Thompson, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers.

There are compelling animal data that exercise promotes a number of beneficial neuronal changes that improve patient-reported outcomes, said Dr. Thompson, the Garfield Weston Professor of Clinical Neurology and Neurorehabilitation at University College London (England).

“A lot of animal work suggests that exercise can have a major impact on repair and recovery in neurons, synaptic signaling, dendritic branching, long-term potentiation,” and can beneficially affect inflammation and demyelination, he said. Besides the direct effect on nerves, exercise builds up muscle mass, strengthens connective tissue, improves movement, and reduces cardiovascular risk. “Exercise improves inactivity, but also may improve the underlying disease process,” he said. “The effect can be quite profound, and we are building a very good evidence base to support the use of exercise in MS.”

Unfortunately, the existing body of literature remains unimpressive, Dr. Thompson admitted. He compared research in physical activity to that of medicinal therapeutics. Disease-modifying therapeutics research is highly regulated, very well funded, adequately powered and replicated, and – once it shows positive results – receives substantial marketing and sales effort. “As a result, there can be a substantial impact on care.”

Research on rehabilitation and symptom management, with physical activity and other similar interventions, is not well funded, relies on diverse outcome measures, has small cohort numbers, and often is unreplicated. Even positive results “are just left to lie there,” he said. “Thus, it has a modest impact on care. I would like to see equal resources for both research areas.”

The recent surge in stroke rehabilitation is an excellent example of how academic focus can change practice for neurologic illness, he said. A 2017 research letter in Lancet Neurology described the current state of research on exercise in MS (Lancet Neurol. 2017;16[10];848-56). An accompanying editorial compared the MS literature to that in stroke (Lancet Neurol. 2017;16[10]:768-9).

During 1990-2005, there were almost no clinical studies in rehabilitation for stroke, Parkinson’s disease, spinal cord injury, and MS. Around 2005, things began to change in stroke, with close to 60 publications in just 1 year. During 2010-2015, the pace of research accelerated dramatically. Researchers, clinicians, and patients began to see the immediate and long-term benefits of early poststroke rehabilitation. These interventions have now been encoded in practice guidelines and are a core part of clinical care, Dr. Thompson said.

[email protected]

NASHVILLE, TENN. – Pediatric multiple sclerosis is a confirmed clinical entity, which virtually always presents as relapsing-remitting disease, Brenda Banwell, MD, said at the at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“MS in children is the same disease as MS in adults,” said Dr. Banwell, chief of neurology at Children’s Hospital of Philadelphia and the Grace R. Loeb Endowed Chair in Neurosciences there. And although she is unaware of a single case of childhood MS presenting as primary progressive disease, the impact of relapsing-remitting childhood MS may ultimately be progressive damage.

Pediatric MS is also quite rare, a characteristic that makes therapeutic progress challenging. Recruiting sufficient patients for a definitive phase 3 trial is incredibly difficult, especially when multiple trials are commencing simultaneously, not only in the United States but around the world.

Nevertheless, there has been excellent news, Dr. Banwell said in a video interview. Fingolimod (Gilenya), the immunomodulator approved for adult relapsing-remitting MS, gained a pediatric approval under the breakthrough therapy designation on May 11, 2018, on the basis of the successful phase 3 PARADIGMS study.

Compared with intramuscular interferon beta-1a, fingolimod cut the annualized relapse rate by 82%. It also was associated with a 53% annualized reduction in new or newly enlarged T2 lesions and 66% decrease in gadolinium-enhancing T1 lesions.

This big win is prompting researchers and clinicians to rethink the pediatric MS treatment paradigm, Dr. Banwell said. Traditional thinking falls along a dose-escalation pattern that follows relapses. However, “we may take a cue from our rheumatology colleagues, who have seen the benefit of starting with more aggressive treatment and higher doses, getting disease control, and then slowly tapering off.”

Whether this option could actually modify disease progression, as it seems to do in some other inflammatory disorders, is an intriguing – but unproven – possibility, she said.

Dr. Banwell disclosed that she received financial remuneration as a central MRI reviewer for the Novartis-sponsored PARADIGMS study.

[email protected]

NASHVILLE, TENN. – Pediatric multiple sclerosis is a confirmed clinical entity, which virtually always presents as relapsing-remitting disease, Brenda Banwell, MD, said at the at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“MS in children is the same disease as MS in adults,” said Dr. Banwell, chief of neurology at Children’s Hospital of Philadelphia and the Grace R. Loeb Endowed Chair in Neurosciences there. And although she is unaware of a single case of childhood MS presenting as primary progressive disease, the impact of relapsing-remitting childhood MS may ultimately be progressive damage.

Pediatric MS is also quite rare, a characteristic that makes therapeutic progress challenging. Recruiting sufficient patients for a definitive phase 3 trial is incredibly difficult, especially when multiple trials are commencing simultaneously, not only in the United States but around the world.

Nevertheless, there has been excellent news, Dr. Banwell said in a video interview. Fingolimod (Gilenya), the immunomodulator approved for adult relapsing-remitting MS, gained a pediatric approval under the breakthrough therapy designation on May 11, 2018, on the basis of the successful phase 3 PARADIGMS study.

Compared with intramuscular interferon beta-1a, fingolimod cut the annualized relapse rate by 82%. It also was associated with a 53% annualized reduction in new or newly enlarged T2 lesions and 66% decrease in gadolinium-enhancing T1 lesions.

This big win is prompting researchers and clinicians to rethink the pediatric MS treatment paradigm, Dr. Banwell said. Traditional thinking falls along a dose-escalation pattern that follows relapses. However, “we may take a cue from our rheumatology colleagues, who have seen the benefit of starting with more aggressive treatment and higher doses, getting disease control, and then slowly tapering off.”

Whether this option could actually modify disease progression, as it seems to do in some other inflammatory disorders, is an intriguing – but unproven – possibility, she said.

Dr. Banwell disclosed that she received financial remuneration as a central MRI reviewer for the Novartis-sponsored PARADIGMS study.

[email protected]

NASHVILLE, TENN. – Pediatric multiple sclerosis is a confirmed clinical entity, which virtually always presents as relapsing-remitting disease, Brenda Banwell, MD, said at the at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“MS in children is the same disease as MS in adults,” said Dr. Banwell, chief of neurology at Children’s Hospital of Philadelphia and the Grace R. Loeb Endowed Chair in Neurosciences there. And although she is unaware of a single case of childhood MS presenting as primary progressive disease, the impact of relapsing-remitting childhood MS may ultimately be progressive damage.

Pediatric MS is also quite rare, a characteristic that makes therapeutic progress challenging. Recruiting sufficient patients for a definitive phase 3 trial is incredibly difficult, especially when multiple trials are commencing simultaneously, not only in the United States but around the world.

Nevertheless, there has been excellent news, Dr. Banwell said in a video interview. Fingolimod (Gilenya), the immunomodulator approved for adult relapsing-remitting MS, gained a pediatric approval under the breakthrough therapy designation on May 11, 2018, on the basis of the successful phase 3 PARADIGMS study.

Compared with intramuscular interferon beta-1a, fingolimod cut the annualized relapse rate by 82%. It also was associated with a 53% annualized reduction in new or newly enlarged T2 lesions and 66% decrease in gadolinium-enhancing T1 lesions.

This big win is prompting researchers and clinicians to rethink the pediatric MS treatment paradigm, Dr. Banwell said. Traditional thinking falls along a dose-escalation pattern that follows relapses. However, “we may take a cue from our rheumatology colleagues, who have seen the benefit of starting with more aggressive treatment and higher doses, getting disease control, and then slowly tapering off.”

Whether this option could actually modify disease progression, as it seems to do in some other inflammatory disorders, is an intriguing – but unproven – possibility, she said.

Dr. Banwell disclosed that she received financial remuneration as a central MRI reviewer for the Novartis-sponsored PARADIGMS study.

[email protected]

NASHVILLE—Single-nucleotide polymorphisms (SNPs) in the CYP2J2 region of chromosome 1 may be associated with an increased risk of multiple sclerosis (MS) and higher levels of prolactin, according to research presented at the 2018 CMSC Annual Meeting. “To our knowledge, this is the first report to show an association between genetic variants within this region and either MS status or the level of serum prolactin,” said Samantha Jack, Research Coordinator at Saunders Medical Center in Wahoo, Nebraska, and colleagues.

Although the cause of MS is unknown, a combination of genetic, environmental, and infectious risk factors may contribute to its pathogenesis, said Ms. Jack and colleagues. Vitamin D has been suggested as the most attractive environmental factor. In addition, the CYP2J2 gene has been identified as having a role in serum vitamin D levels in cattle, and the CYP2J2-containing region on bovine chromosome 3 is syntenic with that on human chromosome 1, the researchers said.

Evaluating SNPs in the CYP2J2 Region

Ms. Jack and colleagues conducted a study to determine whether associations exist between variations in the genomic region of CYP2J2 and MS status or levels of serum markers associated with vitamin D and calcium metabolism such as prolactin, vitamin D, vitamin D–binding protein, alkaline phosphatase, and calcium.

Participants were recruited from Nebraska, Iowa, and Kansas between October 2014 and December 2016 to participate in a single blood draw.

Ms. Jack and colleagues collected blood samples from 220 patients with MS and 238 age- and sex-matched controls. DNA from blood samples was genotyped for 94 SNPs in a 255,348 base-pair region of chromosome 1 that included CYP2J2 and C1orf87. Researchers analyzed serum samples to quantify concentrations of vitamin D, vitamin D–binding protein, alkaline phosphatase, and prolactin. Almost all participants with MS took supplemental vitamin D.

The 458 participants in the study were predominately Caucasian and had an average age of about 50, said Ms. Jack.

SNPs in the CYP2J2 region were associated with an increased risk of MS. These associations were not significant following Bonferroni correction. Several other SNPs in the CYP2J2 region were associated with prolactin levels, but the associations were not significant following the Bonferroni correction. No SNPs in this region showed significant associations between levels of vitamin D, vitamin D–binding protein, calcium, or alkaline phosphatase, but vitamin D levels may have been skewed since many patients with MS were taking vitamin D supplements, said the researchers.

Overall, SNPs downstream of CYP2J2 in the C1orf87 gene were associated with prolactin levels, and SNPs in the intergenic region between CYP212 and C1orf87 may be associated with MS, said the researchers.

Study Limitations and Future Directions

Study limitations include that the study population was homogeneous (ie, middle-aged and white from the Midwest) and that samples were not always taken in the morning after fasting, which may have affected prolactin levels, said Ms. Jack.

“We are in the process of undertaking a genome-wide association study to continue this work,” Ms. Jack said. “We are currently enrolling more subjects to have a well-powered study, and we hope to have a small subset of people who have not taken vitamin D supplementation so that we will be able to analyze those values.”

—Erica Tricarico

NASHVILLE—Single-nucleotide polymorphisms (SNPs) in the CYP2J2 region of chromosome 1 may be associated with an increased risk of multiple sclerosis (MS) and higher levels of prolactin, according to research presented at the 2018 CMSC Annual Meeting. “To our knowledge, this is the first report to show an association between genetic variants within this region and either MS status or the level of serum prolactin,” said Samantha Jack, Research Coordinator at Saunders Medical Center in Wahoo, Nebraska, and colleagues.

Although the cause of MS is unknown, a combination of genetic, environmental, and infectious risk factors may contribute to its pathogenesis, said Ms. Jack and colleagues. Vitamin D has been suggested as the most attractive environmental factor. In addition, the CYP2J2 gene has been identified as having a role in serum vitamin D levels in cattle, and the CYP2J2-containing region on bovine chromosome 3 is syntenic with that on human chromosome 1, the researchers said.

Evaluating SNPs in the CYP2J2 Region

Ms. Jack and colleagues conducted a study to determine whether associations exist between variations in the genomic region of CYP2J2 and MS status or levels of serum markers associated with vitamin D and calcium metabolism such as prolactin, vitamin D, vitamin D–binding protein, alkaline phosphatase, and calcium.

Participants were recruited from Nebraska, Iowa, and Kansas between October 2014 and December 2016 to participate in a single blood draw.

Ms. Jack and colleagues collected blood samples from 220 patients with MS and 238 age- and sex-matched controls. DNA from blood samples was genotyped for 94 SNPs in a 255,348 base-pair region of chromosome 1 that included CYP2J2 and C1orf87. Researchers analyzed serum samples to quantify concentrations of vitamin D, vitamin D–binding protein, alkaline phosphatase, and prolactin. Almost all participants with MS took supplemental vitamin D.

The 458 participants in the study were predominately Caucasian and had an average age of about 50, said Ms. Jack.

SNPs in the CYP2J2 region were associated with an increased risk of MS. These associations were not significant following Bonferroni correction. Several other SNPs in the CYP2J2 region were associated with prolactin levels, but the associations were not significant following the Bonferroni correction. No SNPs in this region showed significant associations between levels of vitamin D, vitamin D–binding protein, calcium, or alkaline phosphatase, but vitamin D levels may have been skewed since many patients with MS were taking vitamin D supplements, said the researchers.

Overall, SNPs downstream of CYP2J2 in the C1orf87 gene were associated with prolactin levels, and SNPs in the intergenic region between CYP212 and C1orf87 may be associated with MS, said the researchers.

Study Limitations and Future Directions

Study limitations include that the study population was homogeneous (ie, middle-aged and white from the Midwest) and that samples were not always taken in the morning after fasting, which may have affected prolactin levels, said Ms. Jack.

“We are in the process of undertaking a genome-wide association study to continue this work,” Ms. Jack said. “We are currently enrolling more subjects to have a well-powered study, and we hope to have a small subset of people who have not taken vitamin D supplementation so that we will be able to analyze those values.”

—Erica Tricarico

NASHVILLE—Single-nucleotide polymorphisms (SNPs) in the CYP2J2 region of chromosome 1 may be associated with an increased risk of multiple sclerosis (MS) and higher levels of prolactin, according to research presented at the 2018 CMSC Annual Meeting. “To our knowledge, this is the first report to show an association between genetic variants within this region and either MS status or the level of serum prolactin,” said Samantha Jack, Research Coordinator at Saunders Medical Center in Wahoo, Nebraska, and colleagues.

Although the cause of MS is unknown, a combination of genetic, environmental, and infectious risk factors may contribute to its pathogenesis, said Ms. Jack and colleagues. Vitamin D has been suggested as the most attractive environmental factor. In addition, the CYP2J2 gene has been identified as having a role in serum vitamin D levels in cattle, and the CYP2J2-containing region on bovine chromosome 3 is syntenic with that on human chromosome 1, the researchers said.

Evaluating SNPs in the CYP2J2 Region

Ms. Jack and colleagues conducted a study to determine whether associations exist between variations in the genomic region of CYP2J2 and MS status or levels of serum markers associated with vitamin D and calcium metabolism such as prolactin, vitamin D, vitamin D–binding protein, alkaline phosphatase, and calcium.

Participants were recruited from Nebraska, Iowa, and Kansas between October 2014 and December 2016 to participate in a single blood draw.

Ms. Jack and colleagues collected blood samples from 220 patients with MS and 238 age- and sex-matched controls. DNA from blood samples was genotyped for 94 SNPs in a 255,348 base-pair region of chromosome 1 that included CYP2J2 and C1orf87. Researchers analyzed serum samples to quantify concentrations of vitamin D, vitamin D–binding protein, alkaline phosphatase, and prolactin. Almost all participants with MS took supplemental vitamin D.

The 458 participants in the study were predominately Caucasian and had an average age of about 50, said Ms. Jack.

SNPs in the CYP2J2 region were associated with an increased risk of MS. These associations were not significant following Bonferroni correction. Several other SNPs in the CYP2J2 region were associated with prolactin levels, but the associations were not significant following the Bonferroni correction. No SNPs in this region showed significant associations between levels of vitamin D, vitamin D–binding protein, calcium, or alkaline phosphatase, but vitamin D levels may have been skewed since many patients with MS were taking vitamin D supplements, said the researchers.

Overall, SNPs downstream of CYP2J2 in the C1orf87 gene were associated with prolactin levels, and SNPs in the intergenic region between CYP212 and C1orf87 may be associated with MS, said the researchers.

Study Limitations and Future Directions

Study limitations include that the study population was homogeneous (ie, middle-aged and white from the Midwest) and that samples were not always taken in the morning after fasting, which may have affected prolactin levels, said Ms. Jack.

“We are in the process of undertaking a genome-wide association study to continue this work,” Ms. Jack said. “We are currently enrolling more subjects to have a well-powered study, and we hope to have a small subset of people who have not taken vitamin D supplementation so that we will be able to analyze those values.”

—Erica Tricarico

NASHVILLE, Tenn. – Recent research into comorbidities in multiple sclerosis – including head-scratching findings about lower cancer rates – is shedding light on the links between the disease and other illnesses, according to an epidemiologist specializing in MS.

“People should be mindful that if they look at having a positive impact on those comorbidities, they may have the ability to benefit patients in context of their MS,” Helen Tremlett, PhD, said in a video interview at the annual meeting of the Consortium of Multiple Sclerosis Centers. She is the Canada Research Chair in Neuroepidemiology and Multiple Sclerosis at the University of British Columbia, Vancouver.

In recent years, research into comorbidities in MS has risen dramatically. Dr. Tremlett found that the number of papers per year in PubMed that address MS and comorbidity has risen from roughly 30 in 2007 to about 80 in 2015, although the numbers dipped to about 50 and 60, respectively, in 2016 and 2017.

A 2015 systematic review of research into MS and comorbidities reported that while “findings were inconsistent overall,” studies suggested that “meningiomas and possibly urinary system cancers, inflammatory bowel disease, irritable bowel syndrome, epilepsy, depression, anxiety, bipolar disorder, early cataracts, and restless legs syndrome were more common than expected in the MS population.” (Mult Scler. 2015 Mar;21[3]:263-81).

Notably, most cancers are missing from this list. In fact, Dr. Tremlett cowrote a 2012 study that found lower risks of all cancers and several specific types of cancer – breast, lung, colorectal, prostate, and melanoma – in MS patients, compared with age- and gender-matched controls (Brain. 2012 Oct;135[Pt 10]:2973-9).

According to Dr. Tremlett, there are several theories about the apparent lower cancer risk in patients with MS. Perhaps their immune systems are hypervigilant, or maybe MS diagnoses inspire healthier lifestyles.

Researchers have been intrigued by another possibility – that cancer diagnoses are being delayed in patients with MS. Indeed, the 2012 study found that tumor sizes at diagnosis in patients with MS were larger than expected in breast, prostate, lung, and colorectal cancer (P = .04).

“We couldn’t record why that’s the case, but there may be some so-called ‘diagnostic neglect,’ ” she said. “You could imagine a scenario where a typical person with MS goes to see their physician and says, ‘I’m tired. I have fatigue,’ and the physician says, ‘Yes, you have MS, that’s what you should expect.’ Someone in the general population might get additional investigation, get blood work done, and their cancer might be found earlier.”

It’s also possible, she said, that cancer isn’t picked up earlier because it can be difficult to screen people with disabilities. “It’s only recently that physicians can offer the Pap smear to women in a wheelchair.”

On another front, there’s evidence linking comorbidities to worsening MS. A 2018 study coauthored by Dr. Tremlett found that patients with more comorbidities had more disability. Specifically, ischemic heart disease and epilepsy were associated with greater Expanded Disability Status Scale scores (Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004885).

Other research coauthored by Dr. Tremlett has linked comorbidities in MS – specifically, hyperlipidemia, migraine, and three or more comorbidities – to higher risk of MS relapse (Neurology. 2017 Dec 12;89[24]:2455-61).

Dr. Tremlett reported having no relevant disclosures.

NASHVILLE, Tenn. – Recent research into comorbidities in multiple sclerosis – including head-scratching findings about lower cancer rates – is shedding light on the links between the disease and other illnesses, according to an epidemiologist specializing in MS.

“People should be mindful that if they look at having a positive impact on those comorbidities, they may have the ability to benefit patients in context of their MS,” Helen Tremlett, PhD, said in a video interview at the annual meeting of the Consortium of Multiple Sclerosis Centers. She is the Canada Research Chair in Neuroepidemiology and Multiple Sclerosis at the University of British Columbia, Vancouver.

In recent years, research into comorbidities in MS has risen dramatically. Dr. Tremlett found that the number of papers per year in PubMed that address MS and comorbidity has risen from roughly 30 in 2007 to about 80 in 2015, although the numbers dipped to about 50 and 60, respectively, in 2016 and 2017.

A 2015 systematic review of research into MS and comorbidities reported that while “findings were inconsistent overall,” studies suggested that “meningiomas and possibly urinary system cancers, inflammatory bowel disease, irritable bowel syndrome, epilepsy, depression, anxiety, bipolar disorder, early cataracts, and restless legs syndrome were more common than expected in the MS population.” (Mult Scler. 2015 Mar;21[3]:263-81).

Notably, most cancers are missing from this list. In fact, Dr. Tremlett cowrote a 2012 study that found lower risks of all cancers and several specific types of cancer – breast, lung, colorectal, prostate, and melanoma – in MS patients, compared with age- and gender-matched controls (Brain. 2012 Oct;135[Pt 10]:2973-9).

According to Dr. Tremlett, there are several theories about the apparent lower cancer risk in patients with MS. Perhaps their immune systems are hypervigilant, or maybe MS diagnoses inspire healthier lifestyles.

Researchers have been intrigued by another possibility – that cancer diagnoses are being delayed in patients with MS. Indeed, the 2012 study found that tumor sizes at diagnosis in patients with MS were larger than expected in breast, prostate, lung, and colorectal cancer (P = .04).

“We couldn’t record why that’s the case, but there may be some so-called ‘diagnostic neglect,’ ” she said. “You could imagine a scenario where a typical person with MS goes to see their physician and says, ‘I’m tired. I have fatigue,’ and the physician says, ‘Yes, you have MS, that’s what you should expect.’ Someone in the general population might get additional investigation, get blood work done, and their cancer might be found earlier.”

It’s also possible, she said, that cancer isn’t picked up earlier because it can be difficult to screen people with disabilities. “It’s only recently that physicians can offer the Pap smear to women in a wheelchair.”

On another front, there’s evidence linking comorbidities to worsening MS. A 2018 study coauthored by Dr. Tremlett found that patients with more comorbidities had more disability. Specifically, ischemic heart disease and epilepsy were associated with greater Expanded Disability Status Scale scores (Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004885).

Other research coauthored by Dr. Tremlett has linked comorbidities in MS – specifically, hyperlipidemia, migraine, and three or more comorbidities – to higher risk of MS relapse (Neurology. 2017 Dec 12;89[24]:2455-61).

Dr. Tremlett reported having no relevant disclosures.

NASHVILLE, Tenn. – Recent research into comorbidities in multiple sclerosis – including head-scratching findings about lower cancer rates – is shedding light on the links between the disease and other illnesses, according to an epidemiologist specializing in MS.

“People should be mindful that if they look at having a positive impact on those comorbidities, they may have the ability to benefit patients in context of their MS,” Helen Tremlett, PhD, said in a video interview at the annual meeting of the Consortium of Multiple Sclerosis Centers. She is the Canada Research Chair in Neuroepidemiology and Multiple Sclerosis at the University of British Columbia, Vancouver.

In recent years, research into comorbidities in MS has risen dramatically. Dr. Tremlett found that the number of papers per year in PubMed that address MS and comorbidity has risen from roughly 30 in 2007 to about 80 in 2015, although the numbers dipped to about 50 and 60, respectively, in 2016 and 2017.

A 2015 systematic review of research into MS and comorbidities reported that while “findings were inconsistent overall,” studies suggested that “meningiomas and possibly urinary system cancers, inflammatory bowel disease, irritable bowel syndrome, epilepsy, depression, anxiety, bipolar disorder, early cataracts, and restless legs syndrome were more common than expected in the MS population.” (Mult Scler. 2015 Mar;21[3]:263-81).

Notably, most cancers are missing from this list. In fact, Dr. Tremlett cowrote a 2012 study that found lower risks of all cancers and several specific types of cancer – breast, lung, colorectal, prostate, and melanoma – in MS patients, compared with age- and gender-matched controls (Brain. 2012 Oct;135[Pt 10]:2973-9).

According to Dr. Tremlett, there are several theories about the apparent lower cancer risk in patients with MS. Perhaps their immune systems are hypervigilant, or maybe MS diagnoses inspire healthier lifestyles.

Researchers have been intrigued by another possibility – that cancer diagnoses are being delayed in patients with MS. Indeed, the 2012 study found that tumor sizes at diagnosis in patients with MS were larger than expected in breast, prostate, lung, and colorectal cancer (P = .04).

“We couldn’t record why that’s the case, but there may be some so-called ‘diagnostic neglect,’ ” she said. “You could imagine a scenario where a typical person with MS goes to see their physician and says, ‘I’m tired. I have fatigue,’ and the physician says, ‘Yes, you have MS, that’s what you should expect.’ Someone in the general population might get additional investigation, get blood work done, and their cancer might be found earlier.”

It’s also possible, she said, that cancer isn’t picked up earlier because it can be difficult to screen people with disabilities. “It’s only recently that physicians can offer the Pap smear to women in a wheelchair.”

On another front, there’s evidence linking comorbidities to worsening MS. A 2018 study coauthored by Dr. Tremlett found that patients with more comorbidities had more disability. Specifically, ischemic heart disease and epilepsy were associated with greater Expanded Disability Status Scale scores (Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004885).

Other research coauthored by Dr. Tremlett has linked comorbidities in MS – specifically, hyperlipidemia, migraine, and three or more comorbidities – to higher risk of MS relapse (Neurology. 2017 Dec 12;89[24]:2455-61).

Dr. Tremlett reported having no relevant disclosures.

NASHVILLE, TENN. – Jeffrey B. English, MD, of the MS Center of Atlanta, knows which quality measures physicians and their patients with multiple sclerosis think are important. After all, he and his colleagues have surveyed them about that very topic.

But he has little time to monitor these measures since he’s too busy with a more overwhelming task: keeping track of unrelated quality measures as required by the federal government.

“When they developed quality measures under the MACRA law, they were not thinking about MS people in general. They were very primary care based,” Dr. English said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In terms of MS, he said, “no one really knows what the correct outcome measures are.”

Dr. English knows more than most about quality measures preferred by neurologists and patients. At the annual CMSC meeting last year, he presented results from a survey of 11 physicians and 423 patients about the measures of care they consider most important. The patient survey asked about several measures recommended by the American Academy of Neurology plus other measures recommended by the physicians.

The two groups – physicians and patients – agreed on the top four measures: change observed via MRI, change observed via exam, quality of life, and fatigue. However, they disagreed on the ranking within the top four spots.

The least important measures for patients were exercise levels, depression, medication compliance, and relapses.

Dr. English wants to “be able to follow what the patients want me to follow.” However, he hasn’t been able to do so since “25% of my time with patients, in between patients and after hours, is spent trying to comply with outcome measures from the new health care system that are of no benefit to the patient,” he said.

He’s referring to the quality measures that many physicians are tracking to get reimbursed by Medicare and Medicaid.

Value-based care posts other challenges for MS physicians, he said, since MS care is especially expensive. Accountable Care Organizations are looking at cost savings in closed systems, he said, and that could spell trouble because patients with MS cost more.

As a 2015 report noted, first-generation disease-modifying therapies (DMTs) for MS cost about $60,000, and “costs for these agents have increased annually at rates 5 to 7 times higher than prescription drug inflation. Newer DMTs commonly entered the market with a cost 25%-60% higher than existing DMTs” (Neurology. 2015 May 26;84[21]:2185-92).

“If I’m in an ACO, and I’m taking care of a lot of MS patients, I’ll already lose money for the accountable care system,” Dr. English said. “They may not necessarily want an MS center inside an ACO.”

What can doctors do? “Advocacy efforts are pretty difficult for physicians,” Dr. English said. “Our hope is that the CMSC will be a clearinghouse for doctors who have ideas and efforts and advocacy, and somehow channel that into the actual provision of care. You have people advocating for medications and for research and for patients, but there’s nobody advocating for the actual care that’s going on, the boots-on-the-ground care. That’s where CMSC should play a big role.”

Dr. English disclosed that he has served as a consultant for multiple pharmaceutical companies.

NASHVILLE, TENN. – Jeffrey B. English, MD, of the MS Center of Atlanta, knows which quality measures physicians and their patients with multiple sclerosis think are important. After all, he and his colleagues have surveyed them about that very topic.

But he has little time to monitor these measures since he’s too busy with a more overwhelming task: keeping track of unrelated quality measures as required by the federal government.

“When they developed quality measures under the MACRA law, they were not thinking about MS people in general. They were very primary care based,” Dr. English said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In terms of MS, he said, “no one really knows what the correct outcome measures are.”

Dr. English knows more than most about quality measures preferred by neurologists and patients. At the annual CMSC meeting last year, he presented results from a survey of 11 physicians and 423 patients about the measures of care they consider most important. The patient survey asked about several measures recommended by the American Academy of Neurology plus other measures recommended by the physicians.

The two groups – physicians and patients – agreed on the top four measures: change observed via MRI, change observed via exam, quality of life, and fatigue. However, they disagreed on the ranking within the top four spots.

The least important measures for patients were exercise levels, depression, medication compliance, and relapses.

Dr. English wants to “be able to follow what the patients want me to follow.” However, he hasn’t been able to do so since “25% of my time with patients, in between patients and after hours, is spent trying to comply with outcome measures from the new health care system that are of no benefit to the patient,” he said.

He’s referring to the quality measures that many physicians are tracking to get reimbursed by Medicare and Medicaid.

Value-based care posts other challenges for MS physicians, he said, since MS care is especially expensive. Accountable Care Organizations are looking at cost savings in closed systems, he said, and that could spell trouble because patients with MS cost more.

As a 2015 report noted, first-generation disease-modifying therapies (DMTs) for MS cost about $60,000, and “costs for these agents have increased annually at rates 5 to 7 times higher than prescription drug inflation. Newer DMTs commonly entered the market with a cost 25%-60% higher than existing DMTs” (Neurology. 2015 May 26;84[21]:2185-92).

“If I’m in an ACO, and I’m taking care of a lot of MS patients, I’ll already lose money for the accountable care system,” Dr. English said. “They may not necessarily want an MS center inside an ACO.”

What can doctors do? “Advocacy efforts are pretty difficult for physicians,” Dr. English said. “Our hope is that the CMSC will be a clearinghouse for doctors who have ideas and efforts and advocacy, and somehow channel that into the actual provision of care. You have people advocating for medications and for research and for patients, but there’s nobody advocating for the actual care that’s going on, the boots-on-the-ground care. That’s where CMSC should play a big role.”

Dr. English disclosed that he has served as a consultant for multiple pharmaceutical companies.

NASHVILLE, TENN. – Jeffrey B. English, MD, of the MS Center of Atlanta, knows which quality measures physicians and their patients with multiple sclerosis think are important. After all, he and his colleagues have surveyed them about that very topic.

But he has little time to monitor these measures since he’s too busy with a more overwhelming task: keeping track of unrelated quality measures as required by the federal government.

“When they developed quality measures under the MACRA law, they were not thinking about MS people in general. They were very primary care based,” Dr. English said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In terms of MS, he said, “no one really knows what the correct outcome measures are.”

Dr. English knows more than most about quality measures preferred by neurologists and patients. At the annual CMSC meeting last year, he presented results from a survey of 11 physicians and 423 patients about the measures of care they consider most important. The patient survey asked about several measures recommended by the American Academy of Neurology plus other measures recommended by the physicians.

The two groups – physicians and patients – agreed on the top four measures: change observed via MRI, change observed via exam, quality of life, and fatigue. However, they disagreed on the ranking within the top four spots.

The least important measures for patients were exercise levels, depression, medication compliance, and relapses.

Dr. English wants to “be able to follow what the patients want me to follow.” However, he hasn’t been able to do so since “25% of my time with patients, in between patients and after hours, is spent trying to comply with outcome measures from the new health care system that are of no benefit to the patient,” he said.

He’s referring to the quality measures that many physicians are tracking to get reimbursed by Medicare and Medicaid.

Value-based care posts other challenges for MS physicians, he said, since MS care is especially expensive. Accountable Care Organizations are looking at cost savings in closed systems, he said, and that could spell trouble because patients with MS cost more.

As a 2015 report noted, first-generation disease-modifying therapies (DMTs) for MS cost about $60,000, and “costs for these agents have increased annually at rates 5 to 7 times higher than prescription drug inflation. Newer DMTs commonly entered the market with a cost 25%-60% higher than existing DMTs” (Neurology. 2015 May 26;84[21]:2185-92).

“If I’m in an ACO, and I’m taking care of a lot of MS patients, I’ll already lose money for the accountable care system,” Dr. English said. “They may not necessarily want an MS center inside an ACO.”

What can doctors do? “Advocacy efforts are pretty difficult for physicians,” Dr. English said. “Our hope is that the CMSC will be a clearinghouse for doctors who have ideas and efforts and advocacy, and somehow channel that into the actual provision of care. You have people advocating for medications and for research and for patients, but there’s nobody advocating for the actual care that’s going on, the boots-on-the-ground care. That’s where CMSC should play a big role.”

Dr. English disclosed that he has served as a consultant for multiple pharmaceutical companies.