Multiple Sclerosis Hub

PARIS—It is possible to gauge the effects of disease-modifying therapies (DMTs) for multiple sclerosis (MS) by measuring serum levels of neurofilament light (NFL), according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. DMTs with greater efficacy appear to be associated with lower serum NFL concentrations.

NFL is a biomarker of axonal damage that has been measured primarily in CSF. In patients with MS, the CSF NFL concentration reflects disease activity and the efficacy of DMTs. Investigators recently developed an ultrasensitive immunoassay that can determine NFL levels in serum.

The investigators measured serum NFL concentrations using an in-house ultrasensitive single molecule array immunoassay. The intra-assay and inter-assay coefficient of variation was less than 10%.

Median serum NFL concentration decreased significantly in treatment-naïve patients who initiated second-line DMTs (ie, from 22.7 ng/L to 18.5 ng/L) or escalated from a first-line to a second-line DMT (ie, from 17.9 ng/L to 12.6 ng/L). The median serum NFL concentration was stable in patients who switched between second-line DMTs (14.9 ng/L before the switch and 13.7 ng/L after the switch). Similarly, the median serum NFL concentration did not change significantly in patients who stayed untreated (40.7 ng/L at first measurement and 37.1 ng/L at second measurement), initiated first-line treatment (20.6 ng/L vs 25.5 ng/L), or switched between first-line DMTs (17.3 ng/L vs 16.7 ng/L).

“The goal of DMTs in MS is to reduce axonal degeneration,” said Dr. Nováková. “Repeated analysis of serum NFL may represent a new possibility to monitor this process and may provide objective support in treatment decisions.”

PARIS—It is possible to gauge the effects of disease-modifying therapies (DMTs) for multiple sclerosis (MS) by measuring serum levels of neurofilament light (NFL), according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. DMTs with greater efficacy appear to be associated with lower serum NFL concentrations.

NFL is a biomarker of axonal damage that has been measured primarily in CSF. In patients with MS, the CSF NFL concentration reflects disease activity and the efficacy of DMTs. Investigators recently developed an ultrasensitive immunoassay that can determine NFL levels in serum.

The investigators measured serum NFL concentrations using an in-house ultrasensitive single molecule array immunoassay. The intra-assay and inter-assay coefficient of variation was less than 10%.

Median serum NFL concentration decreased significantly in treatment-naïve patients who initiated second-line DMTs (ie, from 22.7 ng/L to 18.5 ng/L) or escalated from a first-line to a second-line DMT (ie, from 17.9 ng/L to 12.6 ng/L). The median serum NFL concentration was stable in patients who switched between second-line DMTs (14.9 ng/L before the switch and 13.7 ng/L after the switch). Similarly, the median serum NFL concentration did not change significantly in patients who stayed untreated (40.7 ng/L at first measurement and 37.1 ng/L at second measurement), initiated first-line treatment (20.6 ng/L vs 25.5 ng/L), or switched between first-line DMTs (17.3 ng/L vs 16.7 ng/L).

“The goal of DMTs in MS is to reduce axonal degeneration,” said Dr. Nováková. “Repeated analysis of serum NFL may represent a new possibility to monitor this process and may provide objective support in treatment decisions.”

PARIS—It is possible to gauge the effects of disease-modifying therapies (DMTs) for multiple sclerosis (MS) by measuring serum levels of neurofilament light (NFL), according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. DMTs with greater efficacy appear to be associated with lower serum NFL concentrations.

NFL is a biomarker of axonal damage that has been measured primarily in CSF. In patients with MS, the CSF NFL concentration reflects disease activity and the efficacy of DMTs. Investigators recently developed an ultrasensitive immunoassay that can determine NFL levels in serum.

The investigators measured serum NFL concentrations using an in-house ultrasensitive single molecule array immunoassay. The intra-assay and inter-assay coefficient of variation was less than 10%.

Median serum NFL concentration decreased significantly in treatment-naïve patients who initiated second-line DMTs (ie, from 22.7 ng/L to 18.5 ng/L) or escalated from a first-line to a second-line DMT (ie, from 17.9 ng/L to 12.6 ng/L). The median serum NFL concentration was stable in patients who switched between second-line DMTs (14.9 ng/L before the switch and 13.7 ng/L after the switch). Similarly, the median serum NFL concentration did not change significantly in patients who stayed untreated (40.7 ng/L at first measurement and 37.1 ng/L at second measurement), initiated first-line treatment (20.6 ng/L vs 25.5 ng/L), or switched between first-line DMTs (17.3 ng/L vs 16.7 ng/L).

“The goal of DMTs in MS is to reduce axonal degeneration,” said Dr. Nováková. “Repeated analysis of serum NFL may represent a new possibility to monitor this process and may provide objective support in treatment decisions.”

PARIS—A noninvasive test that assesses immunoglobulin (Ig) free light chains in saliva may detect immunopathologic changes in the multiple sclerosis (MS) disease state and evaluate response to treatment, according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. The technique has a specificity of 80% and sensitivity of 89% for diagnosing active MS, said lead author Esther Ganelin-Cohen, MD, PhD, Director of the Neuro-Immunology Clinic at Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, on behalf of her research colleagues.

The complexity of MS requires different biomarkers to evaluate the various aspects of the disease. CSF analysis is commonly used, but the need for lumbar puncture makes CSF tests impractical for monitoring disease activity and response to treatment. In their search for noninvasive diagnostic methods, Dr. Ganelin-Cohen and colleagues hypothesized that Ig free light chain analysis in saliva may help detect immunopathologic changes in patients with MS. This assumption relied on prior reports indicating changes in mucosal immunity in patients with MS, and on a growing body of evidence for a potential diagnostic role of free light chains in MS.

A new technique based on Western blot analysis was developed to study kappa (k) and lambda (λ) free light chain monomers and dimers in saliva. Normal saliva showed high proportion of dimeric free light chains compared to that in the serum. “This finding might be explained by structural peculiarities of Ig in saliva,” Dr. Ganelin-Cohen said. “In contrast to most serum Ig, saliva IgA2 molecules incorporate the dimeric (not monomeric) light chains that may require production of larger amounts of dimeric light chains by the B cells synthesizing IgA2.”

Dr. Ganelin-Cohen and her colleagues compared free light chain monomer and dimer patterns in the saliva of patients with MS with those in healthy subjects. The intensity of the immunoreactive free light chain was measured, and the free light chain indices accounting for the total free light chain level and for monomer/dimer ratios (k monomer/dimer index and λ monomer/dimer index) were computed.

Most patients with active MS showed abnormally high free light chain levels, or a high proportion of monomeric free light chains. The reasons for such pathologic free light chain changes in patients with active MS are not clear, but they might be due to peripheral B lymphocytes penetrating oral mucosa and producing larger amounts of monomeric free light chains. Statistical analysis of these indices showed significant differences not only between patients with active MS (n = 27) and healthy subjects (n = 28), but also between patients with active MS (n = 27) and those in remission (n = 58).

Cut-off values were established to distinguish a healthy state from the pathologic conditions in MS: total free light chain level index = 17, k monomer/dimer index = 4.0, λ monomer/dimer index = 2.4. Most patients with active MS showed free light chain indices above these cut-off values.

The high specificity and sensitivity of the technique for diagnosing active MS enable this test to become a new noninvasive complementary tool to evaluate MS, Dr. Ganelin-Cohen and colleagues concluded.

PARIS—A noninvasive test that assesses immunoglobulin (Ig) free light chains in saliva may detect immunopathologic changes in the multiple sclerosis (MS) disease state and evaluate response to treatment, according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. The technique has a specificity of 80% and sensitivity of 89% for diagnosing active MS, said lead author Esther Ganelin-Cohen, MD, PhD, Director of the Neuro-Immunology Clinic at Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, on behalf of her research colleagues.

The complexity of MS requires different biomarkers to evaluate the various aspects of the disease. CSF analysis is commonly used, but the need for lumbar puncture makes CSF tests impractical for monitoring disease activity and response to treatment. In their search for noninvasive diagnostic methods, Dr. Ganelin-Cohen and colleagues hypothesized that Ig free light chain analysis in saliva may help detect immunopathologic changes in patients with MS. This assumption relied on prior reports indicating changes in mucosal immunity in patients with MS, and on a growing body of evidence for a potential diagnostic role of free light chains in MS.

A new technique based on Western blot analysis was developed to study kappa (k) and lambda (λ) free light chain monomers and dimers in saliva. Normal saliva showed high proportion of dimeric free light chains compared to that in the serum. “This finding might be explained by structural peculiarities of Ig in saliva,” Dr. Ganelin-Cohen said. “In contrast to most serum Ig, saliva IgA2 molecules incorporate the dimeric (not monomeric) light chains that may require production of larger amounts of dimeric light chains by the B cells synthesizing IgA2.”

Dr. Ganelin-Cohen and her colleagues compared free light chain monomer and dimer patterns in the saliva of patients with MS with those in healthy subjects. The intensity of the immunoreactive free light chain was measured, and the free light chain indices accounting for the total free light chain level and for monomer/dimer ratios (k monomer/dimer index and λ monomer/dimer index) were computed.

Most patients with active MS showed abnormally high free light chain levels, or a high proportion of monomeric free light chains. The reasons for such pathologic free light chain changes in patients with active MS are not clear, but they might be due to peripheral B lymphocytes penetrating oral mucosa and producing larger amounts of monomeric free light chains. Statistical analysis of these indices showed significant differences not only between patients with active MS (n = 27) and healthy subjects (n = 28), but also between patients with active MS (n = 27) and those in remission (n = 58).

Cut-off values were established to distinguish a healthy state from the pathologic conditions in MS: total free light chain level index = 17, k monomer/dimer index = 4.0, λ monomer/dimer index = 2.4. Most patients with active MS showed free light chain indices above these cut-off values.

The high specificity and sensitivity of the technique for diagnosing active MS enable this test to become a new noninvasive complementary tool to evaluate MS, Dr. Ganelin-Cohen and colleagues concluded.

PARIS—A noninvasive test that assesses immunoglobulin (Ig) free light chains in saliva may detect immunopathologic changes in the multiple sclerosis (MS) disease state and evaluate response to treatment, according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. The technique has a specificity of 80% and sensitivity of 89% for diagnosing active MS, said lead author Esther Ganelin-Cohen, MD, PhD, Director of the Neuro-Immunology Clinic at Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, on behalf of her research colleagues.

The complexity of MS requires different biomarkers to evaluate the various aspects of the disease. CSF analysis is commonly used, but the need for lumbar puncture makes CSF tests impractical for monitoring disease activity and response to treatment. In their search for noninvasive diagnostic methods, Dr. Ganelin-Cohen and colleagues hypothesized that Ig free light chain analysis in saliva may help detect immunopathologic changes in patients with MS. This assumption relied on prior reports indicating changes in mucosal immunity in patients with MS, and on a growing body of evidence for a potential diagnostic role of free light chains in MS.

A new technique based on Western blot analysis was developed to study kappa (k) and lambda (λ) free light chain monomers and dimers in saliva. Normal saliva showed high proportion of dimeric free light chains compared to that in the serum. “This finding might be explained by structural peculiarities of Ig in saliva,” Dr. Ganelin-Cohen said. “In contrast to most serum Ig, saliva IgA2 molecules incorporate the dimeric (not monomeric) light chains that may require production of larger amounts of dimeric light chains by the B cells synthesizing IgA2.”

Dr. Ganelin-Cohen and her colleagues compared free light chain monomer and dimer patterns in the saliva of patients with MS with those in healthy subjects. The intensity of the immunoreactive free light chain was measured, and the free light chain indices accounting for the total free light chain level and for monomer/dimer ratios (k monomer/dimer index and λ monomer/dimer index) were computed.

Most patients with active MS showed abnormally high free light chain levels, or a high proportion of monomeric free light chains. The reasons for such pathologic free light chain changes in patients with active MS are not clear, but they might be due to peripheral B lymphocytes penetrating oral mucosa and producing larger amounts of monomeric free light chains. Statistical analysis of these indices showed significant differences not only between patients with active MS (n = 27) and healthy subjects (n = 28), but also between patients with active MS (n = 27) and those in remission (n = 58).

Cut-off values were established to distinguish a healthy state from the pathologic conditions in MS: total free light chain level index = 17, k monomer/dimer index = 4.0, λ monomer/dimer index = 2.4. Most patients with active MS showed free light chain indices above these cut-off values.

The high specificity and sensitivity of the technique for diagnosing active MS enable this test to become a new noninvasive complementary tool to evaluate MS, Dr. Ganelin-Cohen and colleagues concluded.

Older men adapt more poorly to aging with multiple sclerosis (MS), compared with older women, according to research published in the July–August issue of International Journal of MS Care. Health and lifestyle behaviors may put older men with MS at greater risk of health decline, said the authors. Older women, however, appear to have more confidence in their ability to cope with challenges and control the course of their disease.

Healthy Aging With MS

Improved longevity in patients with MS has increased interest in understanding factors associated with healthy aging. Previous studies suggested that factors such as depression, disability, decreased levels of social support, and unemployment predict health-related quality of life in MS.

Two studies examining sex differences in health-related quality of life in young to middle-aged patients with MS found that the association between disability and health-related quality of life was stronger in men than in women. No studies, however, have examined sex differences in health perception among older people with MS, according to the authors.

Analysis of a Canadian Postal Survey

To determine whether older women and men with MS have different health and lifestyle behaviors and whether there are sex differences in contributors to perceived health, Dr. Ploughman and colleagues analyzed data from the Canadian Survey of Health, Lifestyle, and Aging With MS. This cross-sectional study included Canadians older than 55 who had had MS for at least 20 years. Of 921 people contacted, 743 (577 women) returned the mailed questionnaire.

The questionnaire asked about biologic factors (eg, comorbid conditions, years since MS diagnosis), symptoms (eg, depression, anxiety, fatigue, and stress), function (eg, disability and participation), and individual and environmental factors (eg, socioeconomic status, education, and social or health support). Researchers used multiple regression analysis to build explanatory models of health perception.

Older Men With MS Were Less Resilient

Investigators found no differences in disability between men and women, nor differences in age, years of education, or years since MS diagnosis. Older men had lower perceived health and lower resilience, and participated less in life roles than did older women.

In addition, men had more depressive symptoms, and women reported more anxiety. Women also reported higher adherence to a healthy diet (ie, one high in fruits and vegetables and low in meat). Men consumed more alcohol weekly.

Depression was the strongest predictor of health perception in women and men. Other contributors included household participation, fatigue, resilience, and disability in women and physical activity, financial flexibility, and alcohol use in men.

More research is necessary to examine healthy aging in the oldest people with MS, such as octogenarians, said the authors.

—Erica Tricarico

Suggested Reading

Ploughman M, Collins K, Wallack EM, et al. Women’s and men’s differing experiences of health, lifestyle, and aging with multiple sclerosis. Int J MS Care. 2017;19(4):165-171.

Older men adapt more poorly to aging with multiple sclerosis (MS), compared with older women, according to research published in the July–August issue of International Journal of MS Care. Health and lifestyle behaviors may put older men with MS at greater risk of health decline, said the authors. Older women, however, appear to have more confidence in their ability to cope with challenges and control the course of their disease.

Healthy Aging With MS

Improved longevity in patients with MS has increased interest in understanding factors associated with healthy aging. Previous studies suggested that factors such as depression, disability, decreased levels of social support, and unemployment predict health-related quality of life in MS.

Two studies examining sex differences in health-related quality of life in young to middle-aged patients with MS found that the association between disability and health-related quality of life was stronger in men than in women. No studies, however, have examined sex differences in health perception among older people with MS, according to the authors.

Analysis of a Canadian Postal Survey

To determine whether older women and men with MS have different health and lifestyle behaviors and whether there are sex differences in contributors to perceived health, Dr. Ploughman and colleagues analyzed data from the Canadian Survey of Health, Lifestyle, and Aging With MS. This cross-sectional study included Canadians older than 55 who had had MS for at least 20 years. Of 921 people contacted, 743 (577 women) returned the mailed questionnaire.

The questionnaire asked about biologic factors (eg, comorbid conditions, years since MS diagnosis), symptoms (eg, depression, anxiety, fatigue, and stress), function (eg, disability and participation), and individual and environmental factors (eg, socioeconomic status, education, and social or health support). Researchers used multiple regression analysis to build explanatory models of health perception.

Older Men With MS Were Less Resilient

Investigators found no differences in disability between men and women, nor differences in age, years of education, or years since MS diagnosis. Older men had lower perceived health and lower resilience, and participated less in life roles than did older women.

In addition, men had more depressive symptoms, and women reported more anxiety. Women also reported higher adherence to a healthy diet (ie, one high in fruits and vegetables and low in meat). Men consumed more alcohol weekly.

Depression was the strongest predictor of health perception in women and men. Other contributors included household participation, fatigue, resilience, and disability in women and physical activity, financial flexibility, and alcohol use in men.

More research is necessary to examine healthy aging in the oldest people with MS, such as octogenarians, said the authors.

—Erica Tricarico

Suggested Reading

Ploughman M, Collins K, Wallack EM, et al. Women’s and men’s differing experiences of health, lifestyle, and aging with multiple sclerosis. Int J MS Care. 2017;19(4):165-171.

Older men adapt more poorly to aging with multiple sclerosis (MS), compared with older women, according to research published in the July–August issue of International Journal of MS Care. Health and lifestyle behaviors may put older men with MS at greater risk of health decline, said the authors. Older women, however, appear to have more confidence in their ability to cope with challenges and control the course of their disease.

Healthy Aging With MS

Improved longevity in patients with MS has increased interest in understanding factors associated with healthy aging. Previous studies suggested that factors such as depression, disability, decreased levels of social support, and unemployment predict health-related quality of life in MS.

Two studies examining sex differences in health-related quality of life in young to middle-aged patients with MS found that the association between disability and health-related quality of life was stronger in men than in women. No studies, however, have examined sex differences in health perception among older people with MS, according to the authors.

Analysis of a Canadian Postal Survey

To determine whether older women and men with MS have different health and lifestyle behaviors and whether there are sex differences in contributors to perceived health, Dr. Ploughman and colleagues analyzed data from the Canadian Survey of Health, Lifestyle, and Aging With MS. This cross-sectional study included Canadians older than 55 who had had MS for at least 20 years. Of 921 people contacted, 743 (577 women) returned the mailed questionnaire.

The questionnaire asked about biologic factors (eg, comorbid conditions, years since MS diagnosis), symptoms (eg, depression, anxiety, fatigue, and stress), function (eg, disability and participation), and individual and environmental factors (eg, socioeconomic status, education, and social or health support). Researchers used multiple regression analysis to build explanatory models of health perception.

Older Men With MS Were Less Resilient

Investigators found no differences in disability between men and women, nor differences in age, years of education, or years since MS diagnosis. Older men had lower perceived health and lower resilience, and participated less in life roles than did older women.

In addition, men had more depressive symptoms, and women reported more anxiety. Women also reported higher adherence to a healthy diet (ie, one high in fruits and vegetables and low in meat). Men consumed more alcohol weekly.

Depression was the strongest predictor of health perception in women and men. Other contributors included household participation, fatigue, resilience, and disability in women and physical activity, financial flexibility, and alcohol use in men.

More research is necessary to examine healthy aging in the oldest people with MS, such as octogenarians, said the authors.

—Erica Tricarico

Suggested Reading

Ploughman M, Collins K, Wallack EM, et al. Women’s and men’s differing experiences of health, lifestyle, and aging with multiple sclerosis. Int J MS Care. 2017;19(4):165-171.

Urinary urgency with incontinence is associated with recurrent falls in people with relapsing-remitting multiple sclerosis (MS) with mild to moderate disability, according to data published in the July–August issue of International Journal of MS Care. Urinary urgency with incontinence often responds to physical, behavioral, and pharmaceutical interventions, and neurologists should ask patients with MS about bladder symptoms and fall history, according to the authors.

Bladder dysfunction and falls are highly prevalent among people with MS, and bladder dysfunction is associated with falls in older adults. Studies of the association between bladder dysfunction and falls in people with MS, however, are limited and have produced mixed results. Jaime E. Zelaya, PhD, a doctoral student at Oregon Health and Science University in Portland, and colleagues conducted a longitudinal observational cohort study to clarify the possible association between baseline urinary symptoms and future falls.

Participants Prospectively Recorded Falls

The investigators recruited participants from outpatient MS clinics in the Veterans Affairs Portland Health Care System, Oregon Health and Science University MS clinics, and the surrounding community. Eligible participants had a diagnosis of relapsing-remitting MS, mild to moderate MS-related disability, and no relapse within 30 days of baseline. Patients with another condition that affected their balance or gait were excluded from the study.

At baseline, Dr. Zelaya and colleagues asked participants whether they had urinary incontinence, urinary frequency, or urinary urgency. Participants then prospectively recorded their number of falls each day using fall calendars. They were asked to return their calendars to the investigators at the end of each month. The researchers defined four patient categories based on the number of falls during three months. Recurrent fallers fell two or more times, nonrecurrent fallers fell once or not at all, fallers had one fall or more, and nonfallers did not fall. The investigators analyzed the data using age, sex, and disability as potential confounders.

Most Patients Fell at Least Once

The final analysis included 51 participants (37 women). Mean age was 40, and median Expanded Disability Status Scale (EDSS) score was 3.0. In all, 15 participants (29%) were recurrent fallers, and 36 (71%) were nonrecurrent fallers. Furthermore, 32 (63%) participants were fallers, and 19 (37%) were nonfallers.

Urinary dysfunction was more prevalent in fallers and recurrent fallers than in nonrecurrent fallers or nonfallers. In the adjusted analyses, urinary urgency with incontinence was significantly associated with recurrent falls (odds ratio [OR], 57.57). The researchers did not find a significant association between urinary urgency without incontinence and recurrent falls, or between urinary frequency and recurrent falls. They also did not find significant associations between urinary urgency with incontinence, urinary urgency without incontinence, or urinary frequency and sustaining one or more falls.

The high prevalence of falls and bladder dysfunction in this population and previous studies “suggests that both falls and bladder dysfunction are common, early, and persistent symptoms in MS,” said the authors. The findings suggest that fall-prevention programs “should particularly be considered for reducing fall risk in recurrent fallers, and that such programs should include strategies for managing urinary urgency with incontinence,” they concluded.

—Erik Greb

Suggested Reading

Zelaya JE, Murchison C, Cameron M. Associations between bladder dysfunction and falls in people with relapsing-remitting multiple sclerosis. Int J MS Care. 2017;19(4):184-190.

Urinary urgency with incontinence is associated with recurrent falls in people with relapsing-remitting multiple sclerosis (MS) with mild to moderate disability, according to data published in the July–August issue of International Journal of MS Care. Urinary urgency with incontinence often responds to physical, behavioral, and pharmaceutical interventions, and neurologists should ask patients with MS about bladder symptoms and fall history, according to the authors.

Bladder dysfunction and falls are highly prevalent among people with MS, and bladder dysfunction is associated with falls in older adults. Studies of the association between bladder dysfunction and falls in people with MS, however, are limited and have produced mixed results. Jaime E. Zelaya, PhD, a doctoral student at Oregon Health and Science University in Portland, and colleagues conducted a longitudinal observational cohort study to clarify the possible association between baseline urinary symptoms and future falls.

Participants Prospectively Recorded Falls

The investigators recruited participants from outpatient MS clinics in the Veterans Affairs Portland Health Care System, Oregon Health and Science University MS clinics, and the surrounding community. Eligible participants had a diagnosis of relapsing-remitting MS, mild to moderate MS-related disability, and no relapse within 30 days of baseline. Patients with another condition that affected their balance or gait were excluded from the study.

At baseline, Dr. Zelaya and colleagues asked participants whether they had urinary incontinence, urinary frequency, or urinary urgency. Participants then prospectively recorded their number of falls each day using fall calendars. They were asked to return their calendars to the investigators at the end of each month. The researchers defined four patient categories based on the number of falls during three months. Recurrent fallers fell two or more times, nonrecurrent fallers fell once or not at all, fallers had one fall or more, and nonfallers did not fall. The investigators analyzed the data using age, sex, and disability as potential confounders.

Most Patients Fell at Least Once

The final analysis included 51 participants (37 women). Mean age was 40, and median Expanded Disability Status Scale (EDSS) score was 3.0. In all, 15 participants (29%) were recurrent fallers, and 36 (71%) were nonrecurrent fallers. Furthermore, 32 (63%) participants were fallers, and 19 (37%) were nonfallers.

Urinary dysfunction was more prevalent in fallers and recurrent fallers than in nonrecurrent fallers or nonfallers. In the adjusted analyses, urinary urgency with incontinence was significantly associated with recurrent falls (odds ratio [OR], 57.57). The researchers did not find a significant association between urinary urgency without incontinence and recurrent falls, or between urinary frequency and recurrent falls. They also did not find significant associations between urinary urgency with incontinence, urinary urgency without incontinence, or urinary frequency and sustaining one or more falls.

The high prevalence of falls and bladder dysfunction in this population and previous studies “suggests that both falls and bladder dysfunction are common, early, and persistent symptoms in MS,” said the authors. The findings suggest that fall-prevention programs “should particularly be considered for reducing fall risk in recurrent fallers, and that such programs should include strategies for managing urinary urgency with incontinence,” they concluded.

—Erik Greb

Suggested Reading

Zelaya JE, Murchison C, Cameron M. Associations between bladder dysfunction and falls in people with relapsing-remitting multiple sclerosis. Int J MS Care. 2017;19(4):184-190.

Urinary urgency with incontinence is associated with recurrent falls in people with relapsing-remitting multiple sclerosis (MS) with mild to moderate disability, according to data published in the July–August issue of International Journal of MS Care. Urinary urgency with incontinence often responds to physical, behavioral, and pharmaceutical interventions, and neurologists should ask patients with MS about bladder symptoms and fall history, according to the authors.

Bladder dysfunction and falls are highly prevalent among people with MS, and bladder dysfunction is associated with falls in older adults. Studies of the association between bladder dysfunction and falls in people with MS, however, are limited and have produced mixed results. Jaime E. Zelaya, PhD, a doctoral student at Oregon Health and Science University in Portland, and colleagues conducted a longitudinal observational cohort study to clarify the possible association between baseline urinary symptoms and future falls.

Participants Prospectively Recorded Falls

The investigators recruited participants from outpatient MS clinics in the Veterans Affairs Portland Health Care System, Oregon Health and Science University MS clinics, and the surrounding community. Eligible participants had a diagnosis of relapsing-remitting MS, mild to moderate MS-related disability, and no relapse within 30 days of baseline. Patients with another condition that affected their balance or gait were excluded from the study.

At baseline, Dr. Zelaya and colleagues asked participants whether they had urinary incontinence, urinary frequency, or urinary urgency. Participants then prospectively recorded their number of falls each day using fall calendars. They were asked to return their calendars to the investigators at the end of each month. The researchers defined four patient categories based on the number of falls during three months. Recurrent fallers fell two or more times, nonrecurrent fallers fell once or not at all, fallers had one fall or more, and nonfallers did not fall. The investigators analyzed the data using age, sex, and disability as potential confounders.

Most Patients Fell at Least Once

The final analysis included 51 participants (37 women). Mean age was 40, and median Expanded Disability Status Scale (EDSS) score was 3.0. In all, 15 participants (29%) were recurrent fallers, and 36 (71%) were nonrecurrent fallers. Furthermore, 32 (63%) participants were fallers, and 19 (37%) were nonfallers.

Urinary dysfunction was more prevalent in fallers and recurrent fallers than in nonrecurrent fallers or nonfallers. In the adjusted analyses, urinary urgency with incontinence was significantly associated with recurrent falls (odds ratio [OR], 57.57). The researchers did not find a significant association between urinary urgency without incontinence and recurrent falls, or between urinary frequency and recurrent falls. They also did not find significant associations between urinary urgency with incontinence, urinary urgency without incontinence, or urinary frequency and sustaining one or more falls.

The high prevalence of falls and bladder dysfunction in this population and previous studies “suggests that both falls and bladder dysfunction are common, early, and persistent symptoms in MS,” said the authors. The findings suggest that fall-prevention programs “should particularly be considered for reducing fall risk in recurrent fallers, and that such programs should include strategies for managing urinary urgency with incontinence,” they concluded.

—Erik Greb

Suggested Reading

Zelaya JE, Murchison C, Cameron M. Associations between bladder dysfunction and falls in people with relapsing-remitting multiple sclerosis. Int J MS Care. 2017;19(4):184-190.

Patients with multiple sclerosis (MS) with an Expanded Disability Status Scale (EDSS) score between 4 and 6 have significantly slower times on the Timed Up and Go (TUG) test with the addition of a simple cognitive task, according to research published in the July–August issue of International Journal of MS Care. This reduction in performance “might have implications for a person’s more complex everyday activities,” the researchers said.

Patients with MS may develop cognitive impairment (eg, reduced processing speed or working memory), but standard cognitive assessments overlook how cognitive function affects mobility. To assess how the addition of a cognitive task affects mobility in patients with MS, George H. Kraft, MD, Emeritus Alvord Professor of MS Research at the University of Washington in Seattle, and colleagues conducted a study that included 52 adults with MS and 57 healthy controls. Participants had a mean age of about 47, and most were women.

The participants completed three versions of the TUG test: the standard test, the test plus reciting the alphabet, and the test plus subtracting from a number by threes. Times to complete the tests were compared between controls and three groups of participants with MS—those with an EDSS score of 0–3.5 (n = 26), those with an EDSS score of 4.0–5.5 (n = 11), and those with an EDSS score of 6 (n = 15).

Overall mean times for the four groups were 8.0, 8.2, 11.1, and 11.6 seconds, respectively. Controls did not differ from people with MS without mobility problems (ie, those with an EDSS score of 0–3.5), but did differ from the other two groups.

“Individuals with MS and no mobility problems have ... very little increase in time due to the addition of cognitive tasks to the TUG test. The two more severe groups perform similarly to each other, with a steeper increase in time to perform the test when the cognitive demand increases,” the researchers said. “Although we cannot automatically generalize the results to more complex everyday activities, such as walking or driving a car while talking on a cell phone, the reduction in performance is an important issue that should be discussed with the patient and his or her caregiver.”

—Jake Remaly

Suggested Reading

Ciol MA, Matsuda PN, Khurana SR, et al. Effect of cognitive demand on functional mobility in ambulatory individuals with multiple sclerosis. Int J MS Care. 2017;19(4):217-224.

Patients with multiple sclerosis (MS) with an Expanded Disability Status Scale (EDSS) score between 4 and 6 have significantly slower times on the Timed Up and Go (TUG) test with the addition of a simple cognitive task, according to research published in the July–August issue of International Journal of MS Care. This reduction in performance “might have implications for a person’s more complex everyday activities,” the researchers said.

Patients with MS may develop cognitive impairment (eg, reduced processing speed or working memory), but standard cognitive assessments overlook how cognitive function affects mobility. To assess how the addition of a cognitive task affects mobility in patients with MS, George H. Kraft, MD, Emeritus Alvord Professor of MS Research at the University of Washington in Seattle, and colleagues conducted a study that included 52 adults with MS and 57 healthy controls. Participants had a mean age of about 47, and most were women.

The participants completed three versions of the TUG test: the standard test, the test plus reciting the alphabet, and the test plus subtracting from a number by threes. Times to complete the tests were compared between controls and three groups of participants with MS—those with an EDSS score of 0–3.5 (n = 26), those with an EDSS score of 4.0–5.5 (n = 11), and those with an EDSS score of 6 (n = 15).

Overall mean times for the four groups were 8.0, 8.2, 11.1, and 11.6 seconds, respectively. Controls did not differ from people with MS without mobility problems (ie, those with an EDSS score of 0–3.5), but did differ from the other two groups.

“Individuals with MS and no mobility problems have ... very little increase in time due to the addition of cognitive tasks to the TUG test. The two more severe groups perform similarly to each other, with a steeper increase in time to perform the test when the cognitive demand increases,” the researchers said. “Although we cannot automatically generalize the results to more complex everyday activities, such as walking or driving a car while talking on a cell phone, the reduction in performance is an important issue that should be discussed with the patient and his or her caregiver.”

—Jake Remaly

Suggested Reading

Ciol MA, Matsuda PN, Khurana SR, et al. Effect of cognitive demand on functional mobility in ambulatory individuals with multiple sclerosis. Int J MS Care. 2017;19(4):217-224.

Patients with multiple sclerosis (MS) with an Expanded Disability Status Scale (EDSS) score between 4 and 6 have significantly slower times on the Timed Up and Go (TUG) test with the addition of a simple cognitive task, according to research published in the July–August issue of International Journal of MS Care. This reduction in performance “might have implications for a person’s more complex everyday activities,” the researchers said.

Patients with MS may develop cognitive impairment (eg, reduced processing speed or working memory), but standard cognitive assessments overlook how cognitive function affects mobility. To assess how the addition of a cognitive task affects mobility in patients with MS, George H. Kraft, MD, Emeritus Alvord Professor of MS Research at the University of Washington in Seattle, and colleagues conducted a study that included 52 adults with MS and 57 healthy controls. Participants had a mean age of about 47, and most were women.

The participants completed three versions of the TUG test: the standard test, the test plus reciting the alphabet, and the test plus subtracting from a number by threes. Times to complete the tests were compared between controls and three groups of participants with MS—those with an EDSS score of 0–3.5 (n = 26), those with an EDSS score of 4.0–5.5 (n = 11), and those with an EDSS score of 6 (n = 15).

Overall mean times for the four groups were 8.0, 8.2, 11.1, and 11.6 seconds, respectively. Controls did not differ from people with MS without mobility problems (ie, those with an EDSS score of 0–3.5), but did differ from the other two groups.

“Individuals with MS and no mobility problems have ... very little increase in time due to the addition of cognitive tasks to the TUG test. The two more severe groups perform similarly to each other, with a steeper increase in time to perform the test when the cognitive demand increases,” the researchers said. “Although we cannot automatically generalize the results to more complex everyday activities, such as walking or driving a car while talking on a cell phone, the reduction in performance is an important issue that should be discussed with the patient and his or her caregiver.”

—Jake Remaly

Suggested Reading

Ciol MA, Matsuda PN, Khurana SR, et al. Effect of cognitive demand on functional mobility in ambulatory individuals with multiple sclerosis. Int J MS Care. 2017;19(4):217-224.

NEW ORLEANS—Tolerance of risk related to current disease-modifying therapies (DMTs) on the part of patients with multiple sclerosis (MS) varies widely, according to results from a large national survey presented at the 31st Annual Meeting of the Consortium of MS Centers.

“We have therapies available with a wide range of risks,” said Sneha Natarajan, PhD, a research coordinator at the Mellen Center for MS Treatment and Research at the Cleveland Clinic. “Some of the risks are relatively minor, like injection-site reactions or flu-like symptoms, and some are as bad as progressive multifocal leukoencephalopathy [PML], which can be fatal. We do not know what kind of risks people tolerate.”

To address these questions, Dr. Natarajan and colleagues conducted a survey of participants in the North American Research Committee on MS Registry and visitors to the National MS Society website who reported having MS. The benefit of a hypothetical oral DMT was set at 50% reduction in clinical relapses and 30% reduction in disability progression. The researchers chose six risk scenarios to evaluate tolerance to the following six risks: infection, skin rash, kidney injury, thyroid injury, liver injury, and PML. Starting from a risk tolerance of 1:1,000, the risk was adjusted to identify the highest risk tolerated, ranging from “would take regardless of the risk of death” to “no acceptable risk.”

Dr. Natarajan and colleagues reported results from 3,371 survey respondents. The mean age was 55, 93% of participants were white, 61% of participants had relapsing-remitting MS, and 53% of participants were currently taking a DMT. Overall, respondents reported the highest risk tolerance for infection or thyroid risks (1:1,000 for both) and lowest risk tolerance for PML and kidney injury (1:1,000,000 for both). Males reported a higher risk tolerance to all six risks. Females reported a risk tolerance to skin rash that was similar to that of kidney injury and PML.

“There is a pattern to the risks that our patients accept,” Dr. Natarajan said. “I do not think a doctor would not recommend a therapy benefit because of a skin rash [risk], but he may need to address the concerns of the patient up front and have a talk with the patient.”

Researchers also found that current DMT users expressed increased risk tolerance for all outcomes, compared with those not using any DMT. Respondents who were older, those who were more disabled, and those taking infusion therapies also reported higher risk tolerance.

The National MS Society funded this study. Dr. Natarajan reported having no financial disclosures.

—Doug Brunk

NEW ORLEANS—Tolerance of risk related to current disease-modifying therapies (DMTs) on the part of patients with multiple sclerosis (MS) varies widely, according to results from a large national survey presented at the 31st Annual Meeting of the Consortium of MS Centers.

“We have therapies available with a wide range of risks,” said Sneha Natarajan, PhD, a research coordinator at the Mellen Center for MS Treatment and Research at the Cleveland Clinic. “Some of the risks are relatively minor, like injection-site reactions or flu-like symptoms, and some are as bad as progressive multifocal leukoencephalopathy [PML], which can be fatal. We do not know what kind of risks people tolerate.”

To address these questions, Dr. Natarajan and colleagues conducted a survey of participants in the North American Research Committee on MS Registry and visitors to the National MS Society website who reported having MS. The benefit of a hypothetical oral DMT was set at 50% reduction in clinical relapses and 30% reduction in disability progression. The researchers chose six risk scenarios to evaluate tolerance to the following six risks: infection, skin rash, kidney injury, thyroid injury, liver injury, and PML. Starting from a risk tolerance of 1:1,000, the risk was adjusted to identify the highest risk tolerated, ranging from “would take regardless of the risk of death” to “no acceptable risk.”

Dr. Natarajan and colleagues reported results from 3,371 survey respondents. The mean age was 55, 93% of participants were white, 61% of participants had relapsing-remitting MS, and 53% of participants were currently taking a DMT. Overall, respondents reported the highest risk tolerance for infection or thyroid risks (1:1,000 for both) and lowest risk tolerance for PML and kidney injury (1:1,000,000 for both). Males reported a higher risk tolerance to all six risks. Females reported a risk tolerance to skin rash that was similar to that of kidney injury and PML.

“There is a pattern to the risks that our patients accept,” Dr. Natarajan said. “I do not think a doctor would not recommend a therapy benefit because of a skin rash [risk], but he may need to address the concerns of the patient up front and have a talk with the patient.”

Researchers also found that current DMT users expressed increased risk tolerance for all outcomes, compared with those not using any DMT. Respondents who were older, those who were more disabled, and those taking infusion therapies also reported higher risk tolerance.

The National MS Society funded this study. Dr. Natarajan reported having no financial disclosures.

—Doug Brunk

NEW ORLEANS—Tolerance of risk related to current disease-modifying therapies (DMTs) on the part of patients with multiple sclerosis (MS) varies widely, according to results from a large national survey presented at the 31st Annual Meeting of the Consortium of MS Centers.

“We have therapies available with a wide range of risks,” said Sneha Natarajan, PhD, a research coordinator at the Mellen Center for MS Treatment and Research at the Cleveland Clinic. “Some of the risks are relatively minor, like injection-site reactions or flu-like symptoms, and some are as bad as progressive multifocal leukoencephalopathy [PML], which can be fatal. We do not know what kind of risks people tolerate.”

To address these questions, Dr. Natarajan and colleagues conducted a survey of participants in the North American Research Committee on MS Registry and visitors to the National MS Society website who reported having MS. The benefit of a hypothetical oral DMT was set at 50% reduction in clinical relapses and 30% reduction in disability progression. The researchers chose six risk scenarios to evaluate tolerance to the following six risks: infection, skin rash, kidney injury, thyroid injury, liver injury, and PML. Starting from a risk tolerance of 1:1,000, the risk was adjusted to identify the highest risk tolerated, ranging from “would take regardless of the risk of death” to “no acceptable risk.”

Dr. Natarajan and colleagues reported results from 3,371 survey respondents. The mean age was 55, 93% of participants were white, 61% of participants had relapsing-remitting MS, and 53% of participants were currently taking a DMT. Overall, respondents reported the highest risk tolerance for infection or thyroid risks (1:1,000 for both) and lowest risk tolerance for PML and kidney injury (1:1,000,000 for both). Males reported a higher risk tolerance to all six risks. Females reported a risk tolerance to skin rash that was similar to that of kidney injury and PML.

“There is a pattern to the risks that our patients accept,” Dr. Natarajan said. “I do not think a doctor would not recommend a therapy benefit because of a skin rash [risk], but he may need to address the concerns of the patient up front and have a talk with the patient.”

Researchers also found that current DMT users expressed increased risk tolerance for all outcomes, compared with those not using any DMT. Respondents who were older, those who were more disabled, and those taking infusion therapies also reported higher risk tolerance.

The National MS Society funded this study. Dr. Natarajan reported having no financial disclosures.

—Doug Brunk