Multiple Sclerosis Hub

New Orleans – A “Lessons from the Bench” session at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis addressed the ongoing debate regarding the relative importance of neurodegeneration vs. inflammation in progressive multiple sclerosis.

In an interview, session chair Dr. Benjamin Segal discussed the research presented – on topics ranging from immunological biomarkers that could also prove to be therapeutic targets, to immune- and central nervous system–related susceptibility alleles identified in genome wide association studies – and how the findings could lead to new and improved treatments.

“These types of studies give us insights into the immune pathways that are dysregulated in the different diseases and how they may be similar or different from one another. Ultimately all of these scientific studies hopefully will translate into treatments in the future,” said Dr. Segal of the University of Michigan, Ann Arbor.

New Orleans – A “Lessons from the Bench” session at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis addressed the ongoing debate regarding the relative importance of neurodegeneration vs. inflammation in progressive multiple sclerosis.

In an interview, session chair Dr. Benjamin Segal discussed the research presented – on topics ranging from immunological biomarkers that could also prove to be therapeutic targets, to immune- and central nervous system–related susceptibility alleles identified in genome wide association studies – and how the findings could lead to new and improved treatments.

“These types of studies give us insights into the immune pathways that are dysregulated in the different diseases and how they may be similar or different from one another. Ultimately all of these scientific studies hopefully will translate into treatments in the future,” said Dr. Segal of the University of Michigan, Ann Arbor.

New Orleans – A “Lessons from the Bench” session at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis addressed the ongoing debate regarding the relative importance of neurodegeneration vs. inflammation in progressive multiple sclerosis.

In an interview, session chair Dr. Benjamin Segal discussed the research presented – on topics ranging from immunological biomarkers that could also prove to be therapeutic targets, to immune- and central nervous system–related susceptibility alleles identified in genome wide association studies – and how the findings could lead to new and improved treatments.

“These types of studies give us insights into the immune pathways that are dysregulated in the different diseases and how they may be similar or different from one another. Ultimately all of these scientific studies hopefully will translate into treatments in the future,” said Dr. Segal of the University of Michigan, Ann Arbor.

NEW ORLEANS—Contrary to researchers’ hypothesis, fatigue did not result in worsening of spasticity in patients with multiple sclerosis (MS), resulting instead in a nonsignificant decrease. “Clinically, this suggests that the worsening of gait seen over time in persons with MS may be due to reasons other than spasticity,” reported Herbert Karpatkin, PT, DSc, NCS, MSCS, an Assistant Professor at Hunter College in New York, NY, and colleagues at the ACTRIMS 2016 Forum.

Herbert Karpatkin, PT, DSc, NCS, MSCS

Disturbance of gait is known to occur in approximately 80% of patients with MS. Fatigue and spasticity are among the most common and debilitating symptoms in this patient population and both have been known to worsen with physical performance. Anecdotal reports claim that spasticity is associated with worsening fatigue, but the literature provides little information regarding this relationship.

Dr. Karpatkin and colleagues sought to determine whether, as they hypothecized, increases in fatigue in patients with MS result in increases in lower extremity spasticity. If correct, this would mean that physical therapists who perform gait-training activities in patients with MS would need to take the interaction between fatigue and spasticity into account as a factor that may impact outcomes and help determine an appropriate course of treatment.

A convenience sample of 16 ambulatory subjects with MS was recruited from New York City physical therapy practices that specialize in MS. Demographic and subject characteristics including MS type, years since diagnosis, age, gender, Expanded Disability Status Scale (EDSS) score, medications, and use of assistive devices were recorded and analyzed. The Fatigue Severity Scale (FSS), the MS Impact Scale–29 (MSIS–29), and the MS Severity Scale–88 (MSSS–88) were completed for baseline analysis.

Subjects were randomized into walking and resting groups. All subjects received spasticity testing using the Modified Ashworth Scale (MAS). Subjects in the walking group then underwent a six-minute walk to induce fatigue, while subjects in the resting group lay supine for six minutes to minimize fatigue. Immediately following either six-minute condition, MAS testing was repeated. This was performed on three separate trials during a five-day period, followed by a two-week detraining period. Subjects then crossed over to the opposite condition. Fatigue was measured using the Visual Analog Scale of Fatigue (VAS–F) before and after each six-minute condition.

Sixteen subjects (mean EDSS, 3.59) completed the study. Mean MAS scores decreased nonsignificantly following the six-minute walk from 1.054 to 0.827. MAS scores also decreased nonsignificantly in the nonfatigued condition from 0.841 to 0.839. Mean VAS–F scores increased 29.5 mm following the six-minute walk, indicating that MAS testing was performed in a fatigued condition.

NEW ORLEANS—Contrary to researchers’ hypothesis, fatigue did not result in worsening of spasticity in patients with multiple sclerosis (MS), resulting instead in a nonsignificant decrease. “Clinically, this suggests that the worsening of gait seen over time in persons with MS may be due to reasons other than spasticity,” reported Herbert Karpatkin, PT, DSc, NCS, MSCS, an Assistant Professor at Hunter College in New York, NY, and colleagues at the ACTRIMS 2016 Forum.

Herbert Karpatkin, PT, DSc, NCS, MSCS

Disturbance of gait is known to occur in approximately 80% of patients with MS. Fatigue and spasticity are among the most common and debilitating symptoms in this patient population and both have been known to worsen with physical performance. Anecdotal reports claim that spasticity is associated with worsening fatigue, but the literature provides little information regarding this relationship.

Dr. Karpatkin and colleagues sought to determine whether, as they hypothecized, increases in fatigue in patients with MS result in increases in lower extremity spasticity. If correct, this would mean that physical therapists who perform gait-training activities in patients with MS would need to take the interaction between fatigue and spasticity into account as a factor that may impact outcomes and help determine an appropriate course of treatment.

A convenience sample of 16 ambulatory subjects with MS was recruited from New York City physical therapy practices that specialize in MS. Demographic and subject characteristics including MS type, years since diagnosis, age, gender, Expanded Disability Status Scale (EDSS) score, medications, and use of assistive devices were recorded and analyzed. The Fatigue Severity Scale (FSS), the MS Impact Scale–29 (MSIS–29), and the MS Severity Scale–88 (MSSS–88) were completed for baseline analysis.

Subjects were randomized into walking and resting groups. All subjects received spasticity testing using the Modified Ashworth Scale (MAS). Subjects in the walking group then underwent a six-minute walk to induce fatigue, while subjects in the resting group lay supine for six minutes to minimize fatigue. Immediately following either six-minute condition, MAS testing was repeated. This was performed on three separate trials during a five-day period, followed by a two-week detraining period. Subjects then crossed over to the opposite condition. Fatigue was measured using the Visual Analog Scale of Fatigue (VAS–F) before and after each six-minute condition.

Sixteen subjects (mean EDSS, 3.59) completed the study. Mean MAS scores decreased nonsignificantly following the six-minute walk from 1.054 to 0.827. MAS scores also decreased nonsignificantly in the nonfatigued condition from 0.841 to 0.839. Mean VAS–F scores increased 29.5 mm following the six-minute walk, indicating that MAS testing was performed in a fatigued condition.

NEW ORLEANS—Contrary to researchers’ hypothesis, fatigue did not result in worsening of spasticity in patients with multiple sclerosis (MS), resulting instead in a nonsignificant decrease. “Clinically, this suggests that the worsening of gait seen over time in persons with MS may be due to reasons other than spasticity,” reported Herbert Karpatkin, PT, DSc, NCS, MSCS, an Assistant Professor at Hunter College in New York, NY, and colleagues at the ACTRIMS 2016 Forum.

Herbert Karpatkin, PT, DSc, NCS, MSCS

Disturbance of gait is known to occur in approximately 80% of patients with MS. Fatigue and spasticity are among the most common and debilitating symptoms in this patient population and both have been known to worsen with physical performance. Anecdotal reports claim that spasticity is associated with worsening fatigue, but the literature provides little information regarding this relationship.

Dr. Karpatkin and colleagues sought to determine whether, as they hypothecized, increases in fatigue in patients with MS result in increases in lower extremity spasticity. If correct, this would mean that physical therapists who perform gait-training activities in patients with MS would need to take the interaction between fatigue and spasticity into account as a factor that may impact outcomes and help determine an appropriate course of treatment.

A convenience sample of 16 ambulatory subjects with MS was recruited from New York City physical therapy practices that specialize in MS. Demographic and subject characteristics including MS type, years since diagnosis, age, gender, Expanded Disability Status Scale (EDSS) score, medications, and use of assistive devices were recorded and analyzed. The Fatigue Severity Scale (FSS), the MS Impact Scale–29 (MSIS–29), and the MS Severity Scale–88 (MSSS–88) were completed for baseline analysis.

Subjects were randomized into walking and resting groups. All subjects received spasticity testing using the Modified Ashworth Scale (MAS). Subjects in the walking group then underwent a six-minute walk to induce fatigue, while subjects in the resting group lay supine for six minutes to minimize fatigue. Immediately following either six-minute condition, MAS testing was repeated. This was performed on three separate trials during a five-day period, followed by a two-week detraining period. Subjects then crossed over to the opposite condition. Fatigue was measured using the Visual Analog Scale of Fatigue (VAS–F) before and after each six-minute condition.

Sixteen subjects (mean EDSS, 3.59) completed the study. Mean MAS scores decreased nonsignificantly following the six-minute walk from 1.054 to 0.827. MAS scores also decreased nonsignificantly in the nonfatigued condition from 0.841 to 0.839. Mean VAS–F scores increased 29.5 mm following the six-minute walk, indicating that MAS testing was performed in a fatigued condition.

NEW ORLEANS—Levels of anti-Mullerian hormone, a marker of the perimenopausal period, are associated with total gray matter volume and disability in patients with multiple sclerosis (MS), independent of chronological age and disease duration, according to data presented at the ACTRIMS 2016 Forum. The study also indicates that women with MS have no reduction in follicular reserve, compared with healthy women, and therefore have normal fertility.

Women with MS tend to have a more benign initial course than men with MS do, but the former often transition to secondary progressive disease near the time of menopause. To date, research has not clarified whether ovarian decline contributes to the accumulation of disability in women with MS.

Jennifer S. Graves, MD, PhD, a neurologist at the University of California, San Francisco Medical Center, and colleagues initiated a study to determine whether ovarian decline, as measured by levels of anti-Mullerian hormone, is associated with clinical disability or brain atrophy in women with MS. They examined 412 women with MS (mean age, 42.6) and 180 healthy controls (mean age, 44) from a longitudinal research cohort that had as many as 10 years of clinical and MRI follow-up. The investigators measured anti-Mullerian hormone levels in batch using a highly sensitive enzyme-linked immunosorbent assay on plasma samples from baseline, year 3, year 5, and years 8 to 10. They analyzed the data with logistic, linear, and mixed-model regression techniques, with adjustments for age, disease duration, smoking, race, ethnicity, vitamin D level, disease modifying therapy, birth control, and hormone replacement therapy as appropriate.

Jennifer S. Graves, MD, PhD

Dr. Graves and colleagues found that in models controlling for age, anti-Mullerian hormone levels were similar in women with MS and healthy controls. In a multivariable model of women with MS, including rigorous adjustments for age and disease duration, ovarian reserve (per twofold decrease in anti-Mullerian hormone pg/mL) was associated with total normalized gray matter volume (β = -3.29 mm³) and MS Functional Composite z-scores (β = -0.060) at baseline. After adjustment for age, white matter volumes were also associated with anti-Mullerian hormone levels (β = -2.64 mm³) at baseline, but the association did not remain statistically significant after additional adjustments (β = -1.49 mm³).

Having undetectable levels of anti-Mullerian hormone (28% of subjects) was associated with 0.60-point higher Expanded Disability Status Scale score. In a multivariable random-intercept-random-slope model using all observations over time, a twofold decrease in anti-Mullerian hormone (pg/mL) was associated with a 1.85-mm³ decrease in gray matter volume over the follow-up period. The researchers' longitudinal analyses of participants' clinical outcomes is ongoing.

NEW ORLEANS—Levels of anti-Mullerian hormone, a marker of the perimenopausal period, are associated with total gray matter volume and disability in patients with multiple sclerosis (MS), independent of chronological age and disease duration, according to data presented at the ACTRIMS 2016 Forum. The study also indicates that women with MS have no reduction in follicular reserve, compared with healthy women, and therefore have normal fertility.

Women with MS tend to have a more benign initial course than men with MS do, but the former often transition to secondary progressive disease near the time of menopause. To date, research has not clarified whether ovarian decline contributes to the accumulation of disability in women with MS.

Jennifer S. Graves, MD, PhD, a neurologist at the University of California, San Francisco Medical Center, and colleagues initiated a study to determine whether ovarian decline, as measured by levels of anti-Mullerian hormone, is associated with clinical disability or brain atrophy in women with MS. They examined 412 women with MS (mean age, 42.6) and 180 healthy controls (mean age, 44) from a longitudinal research cohort that had as many as 10 years of clinical and MRI follow-up. The investigators measured anti-Mullerian hormone levels in batch using a highly sensitive enzyme-linked immunosorbent assay on plasma samples from baseline, year 3, year 5, and years 8 to 10. They analyzed the data with logistic, linear, and mixed-model regression techniques, with adjustments for age, disease duration, smoking, race, ethnicity, vitamin D level, disease modifying therapy, birth control, and hormone replacement therapy as appropriate.

Jennifer S. Graves, MD, PhD

Dr. Graves and colleagues found that in models controlling for age, anti-Mullerian hormone levels were similar in women with MS and healthy controls. In a multivariable model of women with MS, including rigorous adjustments for age and disease duration, ovarian reserve (per twofold decrease in anti-Mullerian hormone pg/mL) was associated with total normalized gray matter volume (β = -3.29 mm³) and MS Functional Composite z-scores (β = -0.060) at baseline. After adjustment for age, white matter volumes were also associated with anti-Mullerian hormone levels (β = -2.64 mm³) at baseline, but the association did not remain statistically significant after additional adjustments (β = -1.49 mm³).

Having undetectable levels of anti-Mullerian hormone (28% of subjects) was associated with 0.60-point higher Expanded Disability Status Scale score. In a multivariable random-intercept-random-slope model using all observations over time, a twofold decrease in anti-Mullerian hormone (pg/mL) was associated with a 1.85-mm³ decrease in gray matter volume over the follow-up period. The researchers' longitudinal analyses of participants' clinical outcomes is ongoing.

NEW ORLEANS—Levels of anti-Mullerian hormone, a marker of the perimenopausal period, are associated with total gray matter volume and disability in patients with multiple sclerosis (MS), independent of chronological age and disease duration, according to data presented at the ACTRIMS 2016 Forum. The study also indicates that women with MS have no reduction in follicular reserve, compared with healthy women, and therefore have normal fertility.

Women with MS tend to have a more benign initial course than men with MS do, but the former often transition to secondary progressive disease near the time of menopause. To date, research has not clarified whether ovarian decline contributes to the accumulation of disability in women with MS.

Jennifer S. Graves, MD, PhD, a neurologist at the University of California, San Francisco Medical Center, and colleagues initiated a study to determine whether ovarian decline, as measured by levels of anti-Mullerian hormone, is associated with clinical disability or brain atrophy in women with MS. They examined 412 women with MS (mean age, 42.6) and 180 healthy controls (mean age, 44) from a longitudinal research cohort that had as many as 10 years of clinical and MRI follow-up. The investigators measured anti-Mullerian hormone levels in batch using a highly sensitive enzyme-linked immunosorbent assay on plasma samples from baseline, year 3, year 5, and years 8 to 10. They analyzed the data with logistic, linear, and mixed-model regression techniques, with adjustments for age, disease duration, smoking, race, ethnicity, vitamin D level, disease modifying therapy, birth control, and hormone replacement therapy as appropriate.

Jennifer S. Graves, MD, PhD

Dr. Graves and colleagues found that in models controlling for age, anti-Mullerian hormone levels were similar in women with MS and healthy controls. In a multivariable model of women with MS, including rigorous adjustments for age and disease duration, ovarian reserve (per twofold decrease in anti-Mullerian hormone pg/mL) was associated with total normalized gray matter volume (β = -3.29 mm³) and MS Functional Composite z-scores (β = -0.060) at baseline. After adjustment for age, white matter volumes were also associated with anti-Mullerian hormone levels (β = -2.64 mm³) at baseline, but the association did not remain statistically significant after additional adjustments (β = -1.49 mm³).

Having undetectable levels of anti-Mullerian hormone (28% of subjects) was associated with 0.60-point higher Expanded Disability Status Scale score. In a multivariable random-intercept-random-slope model using all observations over time, a twofold decrease in anti-Mullerian hormone (pg/mL) was associated with a 1.85-mm³ decrease in gray matter volume over the follow-up period. The researchers' longitudinal analyses of participants' clinical outcomes is ongoing.

NEW ORLEANS – A decline in levels of anti-müllerian hormone as women approach menopause – a phenomenon dubbed ovarian decline – appears associated with clinical disability and brain atrophy in women with multiple sclerosis, according to the findings of a study of more than 400 women with multiple sclerosis followed up for a decade.

This “accumulation of disability” may explain the often rapid transition from a benign disease course to secondary progressive multiple sclerosis (MS) in women as they approach menopause, Dr. Jennifer S. Graves reported at a meeting held by at the Americas Committee for Treatment and Research in Multiple Sclerosis.

Earlier in life, females often have a more benign initial course of MS than males. The mean age of onset of primary progressive MS and secondary progressive MS are both approximately 45 years. The mean age of menopause is 51 years. Ovarian aging involves up to a 10-year period of decline in ovarian function. After age 50, “women catch up in terms of disability with males” with MS, said Dr. Graves of the University of California, San Francisco. One explanation could be that ovarian aging contributes to the development of progressive disease.

The objective was to determine if ovarian decline as measured by the levels of anti-müllerian hormone (AMH) is associated with clinical disability or brain atrophy in women with MS. The cohort of 412 female patients with MS (mean age, 43 years) was from the UCSF EPIC (Expression, Proteomics, Imaging, Clinical) study, which has followed more than 500 people with MS since 2004 with the aim of identifying factors that drive the disease. Also included were 180 healthy controls with the exact same mean age. AMH levels were measured using an ultrasensitive enzyme-linked immunosorbent assay at baseline and at years 3, 5, 8, 9, and 10. Brain magnetic resonance imaging data also were acquired.

When the data were adjusted for chronologic age, women with MS and healthy controls displayed similar AMH levels (P = .97), implying a normal follicular reserve and rate of ovarian decline in those with MS. White matter volume was associated with AMH levels at baseline (P = .047). The association did not persist when adjusted for age as well as disease duration and body mass index (P = .24), while ovarian reserve was associated with normalized gray matter volume (P = .049) and MS functional composite z scores (P = .036) at baseline. Scrutiny of the follow-up period revealed that a twofold decrease in AMH was associated with a 1.85-mm³ decrease in gray matter volume (P = .060) in MS patients. Almost a third of the MS patients had undetectable levels of AMH, which was associated with a 0.60-point higher expanded disability status scale score (P =.039)

The results support the hypothesized association of ovarian decline with increased severity of MS. Furthermore, AMH may be a useful biomarker of MS progression, said Dr. Graves. “The advantage of this biomarker would be that it captures biological activity in women in their 40s, and so could let you know of imminent change.”

Validation of the findings needs to be done.

The study was funded by the National Institutes of Health, National MS Society, Race to Erase MS, Foundation for the Cedars-Sinai Medical Center, Biogen, and Genentech. Dr. Graves had no relevant financial disclosures.

NEW ORLEANS – A decline in levels of anti-müllerian hormone as women approach menopause – a phenomenon dubbed ovarian decline – appears associated with clinical disability and brain atrophy in women with multiple sclerosis, according to the findings of a study of more than 400 women with multiple sclerosis followed up for a decade.

This “accumulation of disability” may explain the often rapid transition from a benign disease course to secondary progressive multiple sclerosis (MS) in women as they approach menopause, Dr. Jennifer S. Graves reported at a meeting held by at the Americas Committee for Treatment and Research in Multiple Sclerosis.

Earlier in life, females often have a more benign initial course of MS than males. The mean age of onset of primary progressive MS and secondary progressive MS are both approximately 45 years. The mean age of menopause is 51 years. Ovarian aging involves up to a 10-year period of decline in ovarian function. After age 50, “women catch up in terms of disability with males” with MS, said Dr. Graves of the University of California, San Francisco. One explanation could be that ovarian aging contributes to the development of progressive disease.

The objective was to determine if ovarian decline as measured by the levels of anti-müllerian hormone (AMH) is associated with clinical disability or brain atrophy in women with MS. The cohort of 412 female patients with MS (mean age, 43 years) was from the UCSF EPIC (Expression, Proteomics, Imaging, Clinical) study, which has followed more than 500 people with MS since 2004 with the aim of identifying factors that drive the disease. Also included were 180 healthy controls with the exact same mean age. AMH levels were measured using an ultrasensitive enzyme-linked immunosorbent assay at baseline and at years 3, 5, 8, 9, and 10. Brain magnetic resonance imaging data also were acquired.

When the data were adjusted for chronologic age, women with MS and healthy controls displayed similar AMH levels (P = .97), implying a normal follicular reserve and rate of ovarian decline in those with MS. White matter volume was associated with AMH levels at baseline (P = .047). The association did not persist when adjusted for age as well as disease duration and body mass index (P = .24), while ovarian reserve was associated with normalized gray matter volume (P = .049) and MS functional composite z scores (P = .036) at baseline. Scrutiny of the follow-up period revealed that a twofold decrease in AMH was associated with a 1.85-mm³ decrease in gray matter volume (P = .060) in MS patients. Almost a third of the MS patients had undetectable levels of AMH, which was associated with a 0.60-point higher expanded disability status scale score (P =.039)

The results support the hypothesized association of ovarian decline with increased severity of MS. Furthermore, AMH may be a useful biomarker of MS progression, said Dr. Graves. “The advantage of this biomarker would be that it captures biological activity in women in their 40s, and so could let you know of imminent change.”

Validation of the findings needs to be done.

The study was funded by the National Institutes of Health, National MS Society, Race to Erase MS, Foundation for the Cedars-Sinai Medical Center, Biogen, and Genentech. Dr. Graves had no relevant financial disclosures.

NEW ORLEANS – A decline in levels of anti-müllerian hormone as women approach menopause – a phenomenon dubbed ovarian decline – appears associated with clinical disability and brain atrophy in women with multiple sclerosis, according to the findings of a study of more than 400 women with multiple sclerosis followed up for a decade.

This “accumulation of disability” may explain the often rapid transition from a benign disease course to secondary progressive multiple sclerosis (MS) in women as they approach menopause, Dr. Jennifer S. Graves reported at a meeting held by at the Americas Committee for Treatment and Research in Multiple Sclerosis.

Earlier in life, females often have a more benign initial course of MS than males. The mean age of onset of primary progressive MS and secondary progressive MS are both approximately 45 years. The mean age of menopause is 51 years. Ovarian aging involves up to a 10-year period of decline in ovarian function. After age 50, “women catch up in terms of disability with males” with MS, said Dr. Graves of the University of California, San Francisco. One explanation could be that ovarian aging contributes to the development of progressive disease.

The objective was to determine if ovarian decline as measured by the levels of anti-müllerian hormone (AMH) is associated with clinical disability or brain atrophy in women with MS. The cohort of 412 female patients with MS (mean age, 43 years) was from the UCSF EPIC (Expression, Proteomics, Imaging, Clinical) study, which has followed more than 500 people with MS since 2004 with the aim of identifying factors that drive the disease. Also included were 180 healthy controls with the exact same mean age. AMH levels were measured using an ultrasensitive enzyme-linked immunosorbent assay at baseline and at years 3, 5, 8, 9, and 10. Brain magnetic resonance imaging data also were acquired.

When the data were adjusted for chronologic age, women with MS and healthy controls displayed similar AMH levels (P = .97), implying a normal follicular reserve and rate of ovarian decline in those with MS. White matter volume was associated with AMH levels at baseline (P = .047). The association did not persist when adjusted for age as well as disease duration and body mass index (P = .24), while ovarian reserve was associated with normalized gray matter volume (P = .049) and MS functional composite z scores (P = .036) at baseline. Scrutiny of the follow-up period revealed that a twofold decrease in AMH was associated with a 1.85-mm³ decrease in gray matter volume (P = .060) in MS patients. Almost a third of the MS patients had undetectable levels of AMH, which was associated with a 0.60-point higher expanded disability status scale score (P =.039)

The results support the hypothesized association of ovarian decline with increased severity of MS. Furthermore, AMH may be a useful biomarker of MS progression, said Dr. Graves. “The advantage of this biomarker would be that it captures biological activity in women in their 40s, and so could let you know of imminent change.”

Validation of the findings needs to be done.

The study was funded by the National Institutes of Health, National MS Society, Race to Erase MS, Foundation for the Cedars-Sinai Medical Center, Biogen, and Genentech. Dr. Graves had no relevant financial disclosures.

NEW ORLEANS – Exercise can be beneficial in transiently improving cognitive impairment in people with multiple sclerosis.

Research presented at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis has extended the exercise benefit to cognitive impairment, as measured by reaction time in 24 subjects. The benefit, which was transient, also was evident in 14 subjects who were thermosensitive and displayed elevated core body temperature during exercise. Although preliminary, the data are sufficiently evocative to warrant randomized controlled trials (RCTs).

Brian Hoyle/Frontline Medical News

Cognitive impairment is prevalent in MS, being present in upward of 50% of affected individuals. Exercise may or may not be beneficial in cognitive improvement, given the inconsistent results from three RCTs that have been done. The different types of exercise used in the studies could be one reason for the uncertainty.

For people with MS who are fully ambulatory, treadmill walking could be the best form of exercise. But it’s not known how long and at what intensity someone should walk to realize any cognitive benefit. The investigators, led by Brian M. Sandroff, Ph.D., a postdoctoral fellow at the Kessler Foundation, West Orange, N.J., designed the study to assess these unknowns.

The study compared the influence of light, moderate, and vigorous treadmill walking on what is known as inhibitory control – a mental ability to react to stimuli. A period of quiet rest also was included prior to treadmill walking to assess the effects of no walking. The four conditions were tested in random order by the 24 participants with MS who had an Expanded Disability Status Scale (EDSS) score greater than or equal to 4, indicative of minimal or moderate disability. Prior to and soon after 20 minutes of treadmill walking, the reaction time of each participant was judged using a modified flanker task. The test requires a subject to respond to specific relevant information or ignore irrelevant information. The time for a correct response was the reaction time.

Light, moderate, and vigorous treadmill walking similarly and significantly improved reaction time, compared with quiet rest. To assess whether an increase in core body temperature might negate the exercise-related benefit, core body temperature was assessed in 14 thermosensitive MS patients (EDSS less than or equal to 4.0). Core body temperature was recorded every 10 seconds using an ingested sensor capsule and wireless data recorder during 20 minutes of vigorous treadmill exercise and 20 minutes of quiet rest. The core temperature of the subjects rose significantly by about 0.6° C during exercise. But this did not affect the exercise-related improved reaction time.

“There have been no published studies comparing the acute (transient) versus chronic effects of exercise on cognition in MS. We have hypothesized that the acute effects of single bouts of exercise on cognition will be both additive and cumulative over time, when delivered in a longitudinal intervention – much like the effects of a single bout of aerobic exercise on aerobic fitness. In this example, you get small, transient improvements in aerobic fitness after a single session of aerobic exercise; these small improvements add up with continued training, and eventually result in a meaningful improvement,” Dr. Sandroff said in an interview.

The researchers are planning an RCT on the longer-term effects of treadmill walking exercise training on cognition and brain structure/function.

The study was not funded by an external grant. Dr. Sandroff had no relevant financial disclosures.

NEW ORLEANS – Exercise can be beneficial in transiently improving cognitive impairment in people with multiple sclerosis.

Research presented at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis has extended the exercise benefit to cognitive impairment, as measured by reaction time in 24 subjects. The benefit, which was transient, also was evident in 14 subjects who were thermosensitive and displayed elevated core body temperature during exercise. Although preliminary, the data are sufficiently evocative to warrant randomized controlled trials (RCTs).

Brian Hoyle/Frontline Medical News

Cognitive impairment is prevalent in MS, being present in upward of 50% of affected individuals. Exercise may or may not be beneficial in cognitive improvement, given the inconsistent results from three RCTs that have been done. The different types of exercise used in the studies could be one reason for the uncertainty.

For people with MS who are fully ambulatory, treadmill walking could be the best form of exercise. But it’s not known how long and at what intensity someone should walk to realize any cognitive benefit. The investigators, led by Brian M. Sandroff, Ph.D., a postdoctoral fellow at the Kessler Foundation, West Orange, N.J., designed the study to assess these unknowns.

The study compared the influence of light, moderate, and vigorous treadmill walking on what is known as inhibitory control – a mental ability to react to stimuli. A period of quiet rest also was included prior to treadmill walking to assess the effects of no walking. The four conditions were tested in random order by the 24 participants with MS who had an Expanded Disability Status Scale (EDSS) score greater than or equal to 4, indicative of minimal or moderate disability. Prior to and soon after 20 minutes of treadmill walking, the reaction time of each participant was judged using a modified flanker task. The test requires a subject to respond to specific relevant information or ignore irrelevant information. The time for a correct response was the reaction time.

Light, moderate, and vigorous treadmill walking similarly and significantly improved reaction time, compared with quiet rest. To assess whether an increase in core body temperature might negate the exercise-related benefit, core body temperature was assessed in 14 thermosensitive MS patients (EDSS less than or equal to 4.0). Core body temperature was recorded every 10 seconds using an ingested sensor capsule and wireless data recorder during 20 minutes of vigorous treadmill exercise and 20 minutes of quiet rest. The core temperature of the subjects rose significantly by about 0.6° C during exercise. But this did not affect the exercise-related improved reaction time.

“There have been no published studies comparing the acute (transient) versus chronic effects of exercise on cognition in MS. We have hypothesized that the acute effects of single bouts of exercise on cognition will be both additive and cumulative over time, when delivered in a longitudinal intervention – much like the effects of a single bout of aerobic exercise on aerobic fitness. In this example, you get small, transient improvements in aerobic fitness after a single session of aerobic exercise; these small improvements add up with continued training, and eventually result in a meaningful improvement,” Dr. Sandroff said in an interview.

The researchers are planning an RCT on the longer-term effects of treadmill walking exercise training on cognition and brain structure/function.

The study was not funded by an external grant. Dr. Sandroff had no relevant financial disclosures.

NEW ORLEANS – Exercise can be beneficial in transiently improving cognitive impairment in people with multiple sclerosis.

Research presented at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis has extended the exercise benefit to cognitive impairment, as measured by reaction time in 24 subjects. The benefit, which was transient, also was evident in 14 subjects who were thermosensitive and displayed elevated core body temperature during exercise. Although preliminary, the data are sufficiently evocative to warrant randomized controlled trials (RCTs).

Brian Hoyle/Frontline Medical News

Cognitive impairment is prevalent in MS, being present in upward of 50% of affected individuals. Exercise may or may not be beneficial in cognitive improvement, given the inconsistent results from three RCTs that have been done. The different types of exercise used in the studies could be one reason for the uncertainty.

For people with MS who are fully ambulatory, treadmill walking could be the best form of exercise. But it’s not known how long and at what intensity someone should walk to realize any cognitive benefit. The investigators, led by Brian M. Sandroff, Ph.D., a postdoctoral fellow at the Kessler Foundation, West Orange, N.J., designed the study to assess these unknowns.

The study compared the influence of light, moderate, and vigorous treadmill walking on what is known as inhibitory control – a mental ability to react to stimuli. A period of quiet rest also was included prior to treadmill walking to assess the effects of no walking. The four conditions were tested in random order by the 24 participants with MS who had an Expanded Disability Status Scale (EDSS) score greater than or equal to 4, indicative of minimal or moderate disability. Prior to and soon after 20 minutes of treadmill walking, the reaction time of each participant was judged using a modified flanker task. The test requires a subject to respond to specific relevant information or ignore irrelevant information. The time for a correct response was the reaction time.

Light, moderate, and vigorous treadmill walking similarly and significantly improved reaction time, compared with quiet rest. To assess whether an increase in core body temperature might negate the exercise-related benefit, core body temperature was assessed in 14 thermosensitive MS patients (EDSS less than or equal to 4.0). Core body temperature was recorded every 10 seconds using an ingested sensor capsule and wireless data recorder during 20 minutes of vigorous treadmill exercise and 20 minutes of quiet rest. The core temperature of the subjects rose significantly by about 0.6° C during exercise. But this did not affect the exercise-related improved reaction time.

“There have been no published studies comparing the acute (transient) versus chronic effects of exercise on cognition in MS. We have hypothesized that the acute effects of single bouts of exercise on cognition will be both additive and cumulative over time, when delivered in a longitudinal intervention – much like the effects of a single bout of aerobic exercise on aerobic fitness. In this example, you get small, transient improvements in aerobic fitness after a single session of aerobic exercise; these small improvements add up with continued training, and eventually result in a meaningful improvement,” Dr. Sandroff said in an interview.

The researchers are planning an RCT on the longer-term effects of treadmill walking exercise training on cognition and brain structure/function.

The study was not funded by an external grant. Dr. Sandroff had no relevant financial disclosures.

NEW ORLEANS – A focus of the 2016 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum is the pathogenic mechanisms involved in progressive forms of MS, including the genetic and environmental underpinnings and the immunopathologic processes involved, according to ACTRIMS president, Dr. Suhayl Dhib-Jalbut.

In particular, the role of B cells in the pathogenesis of progressive disease will be addressed as recent studies targeting B lymphocytes are providing important new information about the importance of B cells in the pathogenesis of progressive MS.

In this video interview, Dr. Dhib-Jalbut, professor and chair of the department of neurology at the Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., notes that it is hypothesized that in progressive MS, there is a depletion of energy in the central nervous system. Studies of medications that can restore mitochondrial function and energy pools and perhaps have an impact on disease progression will be presented during the forum, he said.

sworcester@frontlinemedcom.com

NEW ORLEANS – A focus of the 2016 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum is the pathogenic mechanisms involved in progressive forms of MS, including the genetic and environmental underpinnings and the immunopathologic processes involved, according to ACTRIMS president, Dr. Suhayl Dhib-Jalbut.

In particular, the role of B cells in the pathogenesis of progressive disease will be addressed as recent studies targeting B lymphocytes are providing important new information about the importance of B cells in the pathogenesis of progressive MS.

In this video interview, Dr. Dhib-Jalbut, professor and chair of the department of neurology at the Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., notes that it is hypothesized that in progressive MS, there is a depletion of energy in the central nervous system. Studies of medications that can restore mitochondrial function and energy pools and perhaps have an impact on disease progression will be presented during the forum, he said.

sworcester@frontlinemedcom.com

NEW ORLEANS – A focus of the 2016 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum is the pathogenic mechanisms involved in progressive forms of MS, including the genetic and environmental underpinnings and the immunopathologic processes involved, according to ACTRIMS president, Dr. Suhayl Dhib-Jalbut.

In particular, the role of B cells in the pathogenesis of progressive disease will be addressed as recent studies targeting B lymphocytes are providing important new information about the importance of B cells in the pathogenesis of progressive MS.

In this video interview, Dr. Dhib-Jalbut, professor and chair of the department of neurology at the Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., notes that it is hypothesized that in progressive MS, there is a depletion of energy in the central nervous system. Studies of medications that can restore mitochondrial function and energy pools and perhaps have an impact on disease progression will be presented during the forum, he said.

sworcester@frontlinemedcom.com

NEW ORLEANS—Intrathecal levels of T and B cells are comparable in progressive multiple sclerosis (MS), compared with relapsing-remitting MS, according to research described at the ACTRIMS 2016 Forum. The major difference between the two forms of the disease, according to the researchers, is that although the immune cells are mobile in relapsing-remitting MS, they are predominantly embedded in CNS tissue in progressive MS. “This compartmentalization of the immune responses is likely the major reason for the failure of current immunomodulatory treatments in both subtypes of progressive MS,” said Mika Komori, MD, PhD, of the Neuroimmunological Unit at the National Institute of Neurological Disorders and Stroke.

Neurologists have interpreted immunomodulatory therapies’ lack of efficacy in progressive MS as evidence that neurodegeneration, rather than immunopathology, stimulates CNS tissue destruction. Dr. Komori and colleagues sought to develop a methodology that reliably quantifies immune-cell infiltration of CNS tissue by combining CSF immunophenotyping with analysis of immune-cell specific soluble markers.

The researchers collected CSF from 198 subjects, including patients with relapsing-remitting MS, secondary progressive MS, primary progressive MS, noninflammatory neurologic disorders, and other inflammatory neurologic disorders, as well as from healthy donors, and processed the samples in a blinded fashion. They optimized electroluminescent assays to quantify 19 soluble biomarkers in the CSF. Cell-specific secretion was assessed in supernatants from sorted primary immune cells. The investigators quantified absolute numbers of CSF immune cells by flow cytometry in 50-fold concentrated CSF and used them to define three ratios between the concentrations of cell-specific soluble CSF biomarkers and absolute numbers of corresponding CSF cells per milliliter of CSF (ie, sCD14:monocyte, sCD21:B-cell, and CD27:T-cell).

The sCD14:monocyte ratio did not differ among diagnostic groups, but the sCD21:B-cell and especially sCD27:T-cell ratios were significantly higher in progressive MS, compared with all other diagnostic groups. The sCD21:B-cell and sCD27:T-cell ratios differentiated patients with progressive MS from those with relapsing-remitting MS with an area under reviewer operator characteristic curve (AUC) comparable to that of current clinically used tests (AUC, 0.76–0.77). An excess of the soluble biomarkers in comparison with the number of CSF cells that produce it implies presence of the second, nonmobile pool of secreting immune cells embedded in CNS tissue. Dr. Komori and colleagues validated the interpretation that higher biomarker ratios parallel infiltration of CNS tissue by corresponding immune cells in patients with available CNS autopsy or biopsy results with 100% concordance.

NEW ORLEANS—Intrathecal levels of T and B cells are comparable in progressive multiple sclerosis (MS), compared with relapsing-remitting MS, according to research described at the ACTRIMS 2016 Forum. The major difference between the two forms of the disease, according to the researchers, is that although the immune cells are mobile in relapsing-remitting MS, they are predominantly embedded in CNS tissue in progressive MS. “This compartmentalization of the immune responses is likely the major reason for the failure of current immunomodulatory treatments in both subtypes of progressive MS,” said Mika Komori, MD, PhD, of the Neuroimmunological Unit at the National Institute of Neurological Disorders and Stroke.

Neurologists have interpreted immunomodulatory therapies’ lack of efficacy in progressive MS as evidence that neurodegeneration, rather than immunopathology, stimulates CNS tissue destruction. Dr. Komori and colleagues sought to develop a methodology that reliably quantifies immune-cell infiltration of CNS tissue by combining CSF immunophenotyping with analysis of immune-cell specific soluble markers.

The researchers collected CSF from 198 subjects, including patients with relapsing-remitting MS, secondary progressive MS, primary progressive MS, noninflammatory neurologic disorders, and other inflammatory neurologic disorders, as well as from healthy donors, and processed the samples in a blinded fashion. They optimized electroluminescent assays to quantify 19 soluble biomarkers in the CSF. Cell-specific secretion was assessed in supernatants from sorted primary immune cells. The investigators quantified absolute numbers of CSF immune cells by flow cytometry in 50-fold concentrated CSF and used them to define three ratios between the concentrations of cell-specific soluble CSF biomarkers and absolute numbers of corresponding CSF cells per milliliter of CSF (ie, sCD14:monocyte, sCD21:B-cell, and CD27:T-cell).

The sCD14:monocyte ratio did not differ among diagnostic groups, but the sCD21:B-cell and especially sCD27:T-cell ratios were significantly higher in progressive MS, compared with all other diagnostic groups. The sCD21:B-cell and sCD27:T-cell ratios differentiated patients with progressive MS from those with relapsing-remitting MS with an area under reviewer operator characteristic curve (AUC) comparable to that of current clinically used tests (AUC, 0.76–0.77). An excess of the soluble biomarkers in comparison with the number of CSF cells that produce it implies presence of the second, nonmobile pool of secreting immune cells embedded in CNS tissue. Dr. Komori and colleagues validated the interpretation that higher biomarker ratios parallel infiltration of CNS tissue by corresponding immune cells in patients with available CNS autopsy or biopsy results with 100% concordance.

NEW ORLEANS—Intrathecal levels of T and B cells are comparable in progressive multiple sclerosis (MS), compared with relapsing-remitting MS, according to research described at the ACTRIMS 2016 Forum. The major difference between the two forms of the disease, according to the researchers, is that although the immune cells are mobile in relapsing-remitting MS, they are predominantly embedded in CNS tissue in progressive MS. “This compartmentalization of the immune responses is likely the major reason for the failure of current immunomodulatory treatments in both subtypes of progressive MS,” said Mika Komori, MD, PhD, of the Neuroimmunological Unit at the National Institute of Neurological Disorders and Stroke.

Neurologists have interpreted immunomodulatory therapies’ lack of efficacy in progressive MS as evidence that neurodegeneration, rather than immunopathology, stimulates CNS tissue destruction. Dr. Komori and colleagues sought to develop a methodology that reliably quantifies immune-cell infiltration of CNS tissue by combining CSF immunophenotyping with analysis of immune-cell specific soluble markers.

The researchers collected CSF from 198 subjects, including patients with relapsing-remitting MS, secondary progressive MS, primary progressive MS, noninflammatory neurologic disorders, and other inflammatory neurologic disorders, as well as from healthy donors, and processed the samples in a blinded fashion. They optimized electroluminescent assays to quantify 19 soluble biomarkers in the CSF. Cell-specific secretion was assessed in supernatants from sorted primary immune cells. The investigators quantified absolute numbers of CSF immune cells by flow cytometry in 50-fold concentrated CSF and used them to define three ratios between the concentrations of cell-specific soluble CSF biomarkers and absolute numbers of corresponding CSF cells per milliliter of CSF (ie, sCD14:monocyte, sCD21:B-cell, and CD27:T-cell).

The sCD14:monocyte ratio did not differ among diagnostic groups, but the sCD21:B-cell and especially sCD27:T-cell ratios were significantly higher in progressive MS, compared with all other diagnostic groups. The sCD21:B-cell and sCD27:T-cell ratios differentiated patients with progressive MS from those with relapsing-remitting MS with an area under reviewer operator characteristic curve (AUC) comparable to that of current clinically used tests (AUC, 0.76–0.77). An excess of the soluble biomarkers in comparison with the number of CSF cells that produce it implies presence of the second, nonmobile pool of secreting immune cells embedded in CNS tissue. Dr. Komori and colleagues validated the interpretation that higher biomarker ratios parallel infiltration of CNS tissue by corresponding immune cells in patients with available CNS autopsy or biopsy results with 100% concordance.

NEW ORLEANS—Light-, moderate-, and vigorous-intensity treadmill walking may particularly improve inhibitory control in fully ambulatory people with multiple sclerosis (MS), according to research described at the ACTRIMS 2016 Forum. Furthermore, the increase in core body temperature associated with such exercise may not negate its potentially beneficial effects on inhibitory control.

“This [study] represents the next step in delineating the optimal exercise stimuli for improving cognition in fully ambulatory persons with MS and supports the feasibility of chronic treadmill walking exercise training for improving inhibitory control in thermosensitive persons with MS,” said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey.

Exercise training is a promising approach for managing cognitive impairment in persons with MS. Although preliminary evidence indicates that treadmill walking might have the greatest beneficial effects on inhibitory control, compared with other forms of exercise, in fully ambulatory persons with MS, the effects of varying intensities of treadmill walking exercise on inhibitory control are unknown. In addition, previous research has not indicated whether increases in core body temperature negate the potentially beneficial effects of treadmill walking exercise on inhibitory control in thermosensitive people with MS.

To better determine the optimal form of exercise for improving cognition in MS, Dr. Sandroff and colleagues first compared the acute effects of light-, moderate-, and vigorous-intensity treadmill walking exercise on inhibitory control in 24 participants with MS using a within-subjects, repeated-measures design. In a second study, the researchers examined the acute effects of core body temperature on inhibitory control during vigorous treadmill walking exercise in 14 thermosensitive persons with MS.

Participants in the first study completed four experimental conditions (ie, 20 minutes of light-, moderate-, and vigorous-intensity treadmill walking exercise and quiet rest) in a randomized, counterbalanced order. The investigators measured inhibitory control before and after each condition using a modified flanker task. In the second study, thermosensitive participants with MS completed two experimental conditions (ie, 20 minutes of vigorous treadmill walking exercise and 20 minutes of quiet rest) in a randomized, counterbalanced order. The researchers measured core body temperature throughout both conditions. Inhibitory control was measured before and after each condition using a modified flanker task.

In the first study, the investigators observed large, statistically significant improvements in inhibitory control for all three intensities of treadmill walking exercise, compared with quiet rest. The improvements were of similar magnitude. The second study indicated that, compared with rest, vigorous exercise was followed by improvements in inhibitory control, despite significant elevations in core body temperature (~0.6 °C) in thermosensitive persons with MS.

NEW ORLEANS—Light-, moderate-, and vigorous-intensity treadmill walking may particularly improve inhibitory control in fully ambulatory people with multiple sclerosis (MS), according to research described at the ACTRIMS 2016 Forum. Furthermore, the increase in core body temperature associated with such exercise may not negate its potentially beneficial effects on inhibitory control.

“This [study] represents the next step in delineating the optimal exercise stimuli for improving cognition in fully ambulatory persons with MS and supports the feasibility of chronic treadmill walking exercise training for improving inhibitory control in thermosensitive persons with MS,” said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey.

Exercise training is a promising approach for managing cognitive impairment in persons with MS. Although preliminary evidence indicates that treadmill walking might have the greatest beneficial effects on inhibitory control, compared with other forms of exercise, in fully ambulatory persons with MS, the effects of varying intensities of treadmill walking exercise on inhibitory control are unknown. In addition, previous research has not indicated whether increases in core body temperature negate the potentially beneficial effects of treadmill walking exercise on inhibitory control in thermosensitive people with MS.

To better determine the optimal form of exercise for improving cognition in MS, Dr. Sandroff and colleagues first compared the acute effects of light-, moderate-, and vigorous-intensity treadmill walking exercise on inhibitory control in 24 participants with MS using a within-subjects, repeated-measures design. In a second study, the researchers examined the acute effects of core body temperature on inhibitory control during vigorous treadmill walking exercise in 14 thermosensitive persons with MS.

Participants in the first study completed four experimental conditions (ie, 20 minutes of light-, moderate-, and vigorous-intensity treadmill walking exercise and quiet rest) in a randomized, counterbalanced order. The investigators measured inhibitory control before and after each condition using a modified flanker task. In the second study, thermosensitive participants with MS completed two experimental conditions (ie, 20 minutes of vigorous treadmill walking exercise and 20 minutes of quiet rest) in a randomized, counterbalanced order. The researchers measured core body temperature throughout both conditions. Inhibitory control was measured before and after each condition using a modified flanker task.

In the first study, the investigators observed large, statistically significant improvements in inhibitory control for all three intensities of treadmill walking exercise, compared with quiet rest. The improvements were of similar magnitude. The second study indicated that, compared with rest, vigorous exercise was followed by improvements in inhibitory control, despite significant elevations in core body temperature (~0.6 °C) in thermosensitive persons with MS.

NEW ORLEANS—Light-, moderate-, and vigorous-intensity treadmill walking may particularly improve inhibitory control in fully ambulatory people with multiple sclerosis (MS), according to research described at the ACTRIMS 2016 Forum. Furthermore, the increase in core body temperature associated with such exercise may not negate its potentially beneficial effects on inhibitory control.

“This [study] represents the next step in delineating the optimal exercise stimuli for improving cognition in fully ambulatory persons with MS and supports the feasibility of chronic treadmill walking exercise training for improving inhibitory control in thermosensitive persons with MS,” said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey.

Exercise training is a promising approach for managing cognitive impairment in persons with MS. Although preliminary evidence indicates that treadmill walking might have the greatest beneficial effects on inhibitory control, compared with other forms of exercise, in fully ambulatory persons with MS, the effects of varying intensities of treadmill walking exercise on inhibitory control are unknown. In addition, previous research has not indicated whether increases in core body temperature negate the potentially beneficial effects of treadmill walking exercise on inhibitory control in thermosensitive people with MS.

To better determine the optimal form of exercise for improving cognition in MS, Dr. Sandroff and colleagues first compared the acute effects of light-, moderate-, and vigorous-intensity treadmill walking exercise on inhibitory control in 24 participants with MS using a within-subjects, repeated-measures design. In a second study, the researchers examined the acute effects of core body temperature on inhibitory control during vigorous treadmill walking exercise in 14 thermosensitive persons with MS.

Participants in the first study completed four experimental conditions (ie, 20 minutes of light-, moderate-, and vigorous-intensity treadmill walking exercise and quiet rest) in a randomized, counterbalanced order. The investigators measured inhibitory control before and after each condition using a modified flanker task. In the second study, thermosensitive participants with MS completed two experimental conditions (ie, 20 minutes of vigorous treadmill walking exercise and 20 minutes of quiet rest) in a randomized, counterbalanced order. The researchers measured core body temperature throughout both conditions. Inhibitory control was measured before and after each condition using a modified flanker task.

In the first study, the investigators observed large, statistically significant improvements in inhibitory control for all three intensities of treadmill walking exercise, compared with quiet rest. The improvements were of similar magnitude. The second study indicated that, compared with rest, vigorous exercise was followed by improvements in inhibitory control, despite significant elevations in core body temperature (~0.6 °C) in thermosensitive persons with MS.

NEW ORLEANS—Disease progression during moderately advanced multiple sclerosis (MS) is amnesic to prior disease activity, according to researchers reporting at the ACTRIMS 2016 Forum. Lower relapse rates and greater persistence on higher-efficacy immunomodulatory therapy after reaching Expanded Disability Status Scale (EDSS) steps 3, 4, and 6 are associated with a decreased risk of accumulating further disability. “Highly effective disease-modifying therapy can mitigate the disability accrual after reaching confirmed EDSS steps of 3, 4, and 6,” said Nathaniel Lizak, BMedSc(Hons), MBBS, of Monash University in Clayton, Australia, and the University of Melbourne, and his research colleagues.

Three large cohort studies have previously examined factors influencing disability accumulation in moderately advanced MS, Dr. Lizak and colleagues noted, but these studies yielded contradictory conclusions. “The effect of therapy during this disease stage remains unclear,” the researchers said.

Dr. Lizak and colleagues sought to identify modifiers of disability trajectories in moderately advanced MS, including disease activity and immunomodulatory therapy during the early and moderately advanced stages of MS. They hypothesized that individual disability trajectories are not homogenous and can be predicted based on demographic and clinical characteristics.

The researchers analyzed epochs between EDSS steps 3 to 6, 4 to 6, and 6 to 6.5. Patients with relapse-onset MS, six-month confirmed progression to the initial EDSS step (baseline), and 12 months pre-baseline follow-up were identified in MSBase, a large international observational MS cohort study. Multivariable survival models examined the impact of relapse rate and proportion of time treated (prior to and during each epoch), age and disease duration at baseline, and progression to the outcome EDSS (6 or 6.5). Sensitivity analyses varying outcome definition and inclusion criteria also were conducted.

For the 3 to 6, 4 to 6, and 6 to 6.5 epochs, 1,560, 1,504, and 1,231 patients were identified, respectively. Pre- and post-baseline disability trajectories showed large coefficients of variance (0.85 to 0.92 and 1.95 to 2.26, respectively) and did not correlate. Probability of reaching the outcome EDSS was not associated with pre-baseline variables, but was increased by higher relapse rates during each epoch (hazard ratios, 1.58 to 3.07). Greater proportion of each epoch treated with higher-efficacy therapies was associated with lower risk of the outcome EDSS (hazard ratios, 0.27 to 0.68). These results were confirmed by sensitivity analyses.

“These observations justify treatment even after moderately advanced disability has been attained,” Dr. Lizak and colleagues concluded.

NEW ORLEANS—Disease progression during moderately advanced multiple sclerosis (MS) is amnesic to prior disease activity, according to researchers reporting at the ACTRIMS 2016 Forum. Lower relapse rates and greater persistence on higher-efficacy immunomodulatory therapy after reaching Expanded Disability Status Scale (EDSS) steps 3, 4, and 6 are associated with a decreased risk of accumulating further disability. “Highly effective disease-modifying therapy can mitigate the disability accrual after reaching confirmed EDSS steps of 3, 4, and 6,” said Nathaniel Lizak, BMedSc(Hons), MBBS, of Monash University in Clayton, Australia, and the University of Melbourne, and his research colleagues.

Three large cohort studies have previously examined factors influencing disability accumulation in moderately advanced MS, Dr. Lizak and colleagues noted, but these studies yielded contradictory conclusions. “The effect of therapy during this disease stage remains unclear,” the researchers said.

Dr. Lizak and colleagues sought to identify modifiers of disability trajectories in moderately advanced MS, including disease activity and immunomodulatory therapy during the early and moderately advanced stages of MS. They hypothesized that individual disability trajectories are not homogenous and can be predicted based on demographic and clinical characteristics.

The researchers analyzed epochs between EDSS steps 3 to 6, 4 to 6, and 6 to 6.5. Patients with relapse-onset MS, six-month confirmed progression to the initial EDSS step (baseline), and 12 months pre-baseline follow-up were identified in MSBase, a large international observational MS cohort study. Multivariable survival models examined the impact of relapse rate and proportion of time treated (prior to and during each epoch), age and disease duration at baseline, and progression to the outcome EDSS (6 or 6.5). Sensitivity analyses varying outcome definition and inclusion criteria also were conducted.

For the 3 to 6, 4 to 6, and 6 to 6.5 epochs, 1,560, 1,504, and 1,231 patients were identified, respectively. Pre- and post-baseline disability trajectories showed large coefficients of variance (0.85 to 0.92 and 1.95 to 2.26, respectively) and did not correlate. Probability of reaching the outcome EDSS was not associated with pre-baseline variables, but was increased by higher relapse rates during each epoch (hazard ratios, 1.58 to 3.07). Greater proportion of each epoch treated with higher-efficacy therapies was associated with lower risk of the outcome EDSS (hazard ratios, 0.27 to 0.68). These results were confirmed by sensitivity analyses.

“These observations justify treatment even after moderately advanced disability has been attained,” Dr. Lizak and colleagues concluded.

NEW ORLEANS—Disease progression during moderately advanced multiple sclerosis (MS) is amnesic to prior disease activity, according to researchers reporting at the ACTRIMS 2016 Forum. Lower relapse rates and greater persistence on higher-efficacy immunomodulatory therapy after reaching Expanded Disability Status Scale (EDSS) steps 3, 4, and 6 are associated with a decreased risk of accumulating further disability. “Highly effective disease-modifying therapy can mitigate the disability accrual after reaching confirmed EDSS steps of 3, 4, and 6,” said Nathaniel Lizak, BMedSc(Hons), MBBS, of Monash University in Clayton, Australia, and the University of Melbourne, and his research colleagues.

Three large cohort studies have previously examined factors influencing disability accumulation in moderately advanced MS, Dr. Lizak and colleagues noted, but these studies yielded contradictory conclusions. “The effect of therapy during this disease stage remains unclear,” the researchers said.

Dr. Lizak and colleagues sought to identify modifiers of disability trajectories in moderately advanced MS, including disease activity and immunomodulatory therapy during the early and moderately advanced stages of MS. They hypothesized that individual disability trajectories are not homogenous and can be predicted based on demographic and clinical characteristics.

The researchers analyzed epochs between EDSS steps 3 to 6, 4 to 6, and 6 to 6.5. Patients with relapse-onset MS, six-month confirmed progression to the initial EDSS step (baseline), and 12 months pre-baseline follow-up were identified in MSBase, a large international observational MS cohort study. Multivariable survival models examined the impact of relapse rate and proportion of time treated (prior to and during each epoch), age and disease duration at baseline, and progression to the outcome EDSS (6 or 6.5). Sensitivity analyses varying outcome definition and inclusion criteria also were conducted.

For the 3 to 6, 4 to 6, and 6 to 6.5 epochs, 1,560, 1,504, and 1,231 patients were identified, respectively. Pre- and post-baseline disability trajectories showed large coefficients of variance (0.85 to 0.92 and 1.95 to 2.26, respectively) and did not correlate. Probability of reaching the outcome EDSS was not associated with pre-baseline variables, but was increased by higher relapse rates during each epoch (hazard ratios, 1.58 to 3.07). Greater proportion of each epoch treated with higher-efficacy therapies was associated with lower risk of the outcome EDSS (hazard ratios, 0.27 to 0.68). These results were confirmed by sensitivity analyses.

“These observations justify treatment even after moderately advanced disability has been attained,” Dr. Lizak and colleagues concluded.