ICYMI Multiple Sclerosis

There may be a benefit to exclusive breastfeeding for women with multiple sclerosis (MS). Women with MS who breastfed their infants exclusively for two months had a lower risk of relapse during the first six months after giving birth, compared with women who did not breastfeed exclusively, according to an article published online ahead of print August 31 in JAMA Neurology.

Previous investigations found that about 20% to 30% of women with MS experience a relapse within three to four months post partum. Currently, there are no therapies or interventions to prevent a relapse, and data on the effect of breastfeeding on postpartum MS relapse are conflicting.

Kerstin Hellwig, MD, a neurologist at St. Josef-Hospital at Ruhr-University Bochum in Germany, and colleagues collected data from 201 pregnant women with relapsing-remitting MS. Each woman was monitored for any relapse for as long as one year after birth. Of these participants, 120 (59.7%) chose to breastfeed exclusively for at least two months, while 42 (20.9%) opted for a combined breastfeeding–supplemental regimen, and 39 (19.4%) did not intend to breastfeed at all. Most of the women (88.6%) in the study cohort had used disease-modifying therapies (DMTs) before pregnancy.

Of the women who breastfed exclusively, 29 (24.2%) experienced a relapse within six months post partum, compared with 31 (38.3%) of those who did not breastfeed exclusively. The effect of exclusive breastfeeding “seems to be plausible,” Dr. Hellwig and coauthors said, since disease activity returned in the second half of the postpartum year in exclusively breastfeeding women, corresponding to the introduction of supplemental feedings and the return of menses.

Dr. Hellwig and colleagues also reported that, compared with women who breastfed exclusively, those who resumed DMTs early had a higher risk of postpartum relapse.

“Relapse in the first six months post partum may be diminished by exclusive breastfeeding, but once regular feedings are introduced, disease activity is likely to return,” Dr. Hellwig and colleagues said. “Taken together, our findings suggest that exclusive breastfeeding acts like a modestly effective treatment with a natural end date.” The researchers concluded that “Women with MS should be supported if they choose to breastfeed exclusively, since it clearly does not increase the risk of postpartum relapse.”

—Ashley Payton

There may be a benefit to exclusive breastfeeding for women with multiple sclerosis (MS). Women with MS who breastfed their infants exclusively for two months had a lower risk of relapse during the first six months after giving birth, compared with women who did not breastfeed exclusively, according to an article published online ahead of print August 31 in JAMA Neurology.

Previous investigations found that about 20% to 30% of women with MS experience a relapse within three to four months post partum. Currently, there are no therapies or interventions to prevent a relapse, and data on the effect of breastfeeding on postpartum MS relapse are conflicting.

Kerstin Hellwig, MD, a neurologist at St. Josef-Hospital at Ruhr-University Bochum in Germany, and colleagues collected data from 201 pregnant women with relapsing-remitting MS. Each woman was monitored for any relapse for as long as one year after birth. Of these participants, 120 (59.7%) chose to breastfeed exclusively for at least two months, while 42 (20.9%) opted for a combined breastfeeding–supplemental regimen, and 39 (19.4%) did not intend to breastfeed at all. Most of the women (88.6%) in the study cohort had used disease-modifying therapies (DMTs) before pregnancy.

Of the women who breastfed exclusively, 29 (24.2%) experienced a relapse within six months post partum, compared with 31 (38.3%) of those who did not breastfeed exclusively. The effect of exclusive breastfeeding “seems to be plausible,” Dr. Hellwig and coauthors said, since disease activity returned in the second half of the postpartum year in exclusively breastfeeding women, corresponding to the introduction of supplemental feedings and the return of menses.

Dr. Hellwig and colleagues also reported that, compared with women who breastfed exclusively, those who resumed DMTs early had a higher risk of postpartum relapse.

“Relapse in the first six months post partum may be diminished by exclusive breastfeeding, but once regular feedings are introduced, disease activity is likely to return,” Dr. Hellwig and colleagues said. “Taken together, our findings suggest that exclusive breastfeeding acts like a modestly effective treatment with a natural end date.” The researchers concluded that “Women with MS should be supported if they choose to breastfeed exclusively, since it clearly does not increase the risk of postpartum relapse.”

—Ashley Payton

There may be a benefit to exclusive breastfeeding for women with multiple sclerosis (MS). Women with MS who breastfed their infants exclusively for two months had a lower risk of relapse during the first six months after giving birth, compared with women who did not breastfeed exclusively, according to an article published online ahead of print August 31 in JAMA Neurology.

Previous investigations found that about 20% to 30% of women with MS experience a relapse within three to four months post partum. Currently, there are no therapies or interventions to prevent a relapse, and data on the effect of breastfeeding on postpartum MS relapse are conflicting.

Kerstin Hellwig, MD, a neurologist at St. Josef-Hospital at Ruhr-University Bochum in Germany, and colleagues collected data from 201 pregnant women with relapsing-remitting MS. Each woman was monitored for any relapse for as long as one year after birth. Of these participants, 120 (59.7%) chose to breastfeed exclusively for at least two months, while 42 (20.9%) opted for a combined breastfeeding–supplemental regimen, and 39 (19.4%) did not intend to breastfeed at all. Most of the women (88.6%) in the study cohort had used disease-modifying therapies (DMTs) before pregnancy.

Of the women who breastfed exclusively, 29 (24.2%) experienced a relapse within six months post partum, compared with 31 (38.3%) of those who did not breastfeed exclusively. The effect of exclusive breastfeeding “seems to be plausible,” Dr. Hellwig and coauthors said, since disease activity returned in the second half of the postpartum year in exclusively breastfeeding women, corresponding to the introduction of supplemental feedings and the return of menses.

Dr. Hellwig and colleagues also reported that, compared with women who breastfed exclusively, those who resumed DMTs early had a higher risk of postpartum relapse.

“Relapse in the first six months post partum may be diminished by exclusive breastfeeding, but once regular feedings are introduced, disease activity is likely to return,” Dr. Hellwig and colleagues said. “Taken together, our findings suggest that exclusive breastfeeding acts like a modestly effective treatment with a natural end date.” The researchers concluded that “Women with MS should be supported if they choose to breastfeed exclusively, since it clearly does not increase the risk of postpartum relapse.”

—Ashley Payton

CHICAGO—Transcranial direct-current stimulation (tDCS) reduces fatigue and improves aspects of verbal memory in patients with multiple sclerosis (MS), according to data from a pilot study presented at the 140th Annual Meeting of the American Neurological Association. The stimulation may not consistently improve working memory, however, contrary to the researchers’ expectations.

Cognitive dysfunction, including working memory deficits, and fatigue are common and debilitating symptoms of MS, said Tracy D. Vannorsdall, PhD, Assistant Professor of Neurology and Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine in Baltimore. Prior studies have shown that tDCS enhances working memory in healthy adults. To see if tDCS might improve working memory in patients with MS, Dr. Vannorsdall and her research colleagues conducted a sham-controlled, single-blind crossover study.

A Sham Stimulation Control

The investigators recruited five patients with secondary progressive MS from the Johns Hopkins MS Center. All participants were right-handed native English speakers, and three of the participants were women. Participants were between the ages of 42 and 57, with an average age of 50. They had a mean estimated IQ of 119 and a mean 18.4 years of schooling.

Participants completed cognitive testing before and after receiving 2 mA of anodal or sham stimulation to the left dorsolateral prefrontal cortex for 30 minutes once per day for five consecutive days. Investigators administered the current using a NeuroConn Stimulator Plus. For the sham stimulation, researchers increased the anodal current to 2 mA and decreased it to 0 mA over 30 seconds. After a four-week washout period, participants repeated the study procedures under the stimulation condition to which they had not been assigned originally.

Evaluating Cognition

Participants completed the Minimal Assessment of Cognitive Functioning in MS, a seven-subtest battery that assesses verbal learning and memory, visuospatial learning and memory, working memory, processing speed, verbal fluency, executive functioning, and perceptual accuracy. Participants also completed self-report measures of mood and fatigue and responded to a mental and physical side effects questionnaire. The researchers performed two-tailed paired-samples t-tests to compare changes in scores across anodal and sham conditions.

No adverse events occurred. Depression scale ratings did not significantly change during tDCS, compared with sham stimulation.

Fatigue Severity Scale

Participants’ scores on the Fatigue Severity Scale increased by 7 points over the course of five days of sham stimulation, compared with a decrease of 4.6 points over the course of anodal stimulation.

In addition, researchers observed a trend toward improved verbal immediate recall under the anodal condition, compared with sham stimulation. Anodal stimulation also was associated with better performance across most cognitive tests, but the differences were not significant. The study was underpowered to detect whether reduced fatigue contributed to the improvements in cognition. “These preliminary findings suggest that tDCS may ameliorate fatigue and cognitive dysfunction in secondary progressive MS,” concluded the researchers. Future studies will investigate the mechanism of these effects.

—Jake Remaly

CHICAGO—Transcranial direct-current stimulation (tDCS) reduces fatigue and improves aspects of verbal memory in patients with multiple sclerosis (MS), according to data from a pilot study presented at the 140th Annual Meeting of the American Neurological Association. The stimulation may not consistently improve working memory, however, contrary to the researchers’ expectations.

Cognitive dysfunction, including working memory deficits, and fatigue are common and debilitating symptoms of MS, said Tracy D. Vannorsdall, PhD, Assistant Professor of Neurology and Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine in Baltimore. Prior studies have shown that tDCS enhances working memory in healthy adults. To see if tDCS might improve working memory in patients with MS, Dr. Vannorsdall and her research colleagues conducted a sham-controlled, single-blind crossover study.

A Sham Stimulation Control

The investigators recruited five patients with secondary progressive MS from the Johns Hopkins MS Center. All participants were right-handed native English speakers, and three of the participants were women. Participants were between the ages of 42 and 57, with an average age of 50. They had a mean estimated IQ of 119 and a mean 18.4 years of schooling.

Participants completed cognitive testing before and after receiving 2 mA of anodal or sham stimulation to the left dorsolateral prefrontal cortex for 30 minutes once per day for five consecutive days. Investigators administered the current using a NeuroConn Stimulator Plus. For the sham stimulation, researchers increased the anodal current to 2 mA and decreased it to 0 mA over 30 seconds. After a four-week washout period, participants repeated the study procedures under the stimulation condition to which they had not been assigned originally.

Evaluating Cognition

Participants completed the Minimal Assessment of Cognitive Functioning in MS, a seven-subtest battery that assesses verbal learning and memory, visuospatial learning and memory, working memory, processing speed, verbal fluency, executive functioning, and perceptual accuracy. Participants also completed self-report measures of mood and fatigue and responded to a mental and physical side effects questionnaire. The researchers performed two-tailed paired-samples t-tests to compare changes in scores across anodal and sham conditions.

No adverse events occurred. Depression scale ratings did not significantly change during tDCS, compared with sham stimulation.

Fatigue Severity Scale

Participants’ scores on the Fatigue Severity Scale increased by 7 points over the course of five days of sham stimulation, compared with a decrease of 4.6 points over the course of anodal stimulation.

In addition, researchers observed a trend toward improved verbal immediate recall under the anodal condition, compared with sham stimulation. Anodal stimulation also was associated with better performance across most cognitive tests, but the differences were not significant. The study was underpowered to detect whether reduced fatigue contributed to the improvements in cognition. “These preliminary findings suggest that tDCS may ameliorate fatigue and cognitive dysfunction in secondary progressive MS,” concluded the researchers. Future studies will investigate the mechanism of these effects.

—Jake Remaly

CHICAGO—Transcranial direct-current stimulation (tDCS) reduces fatigue and improves aspects of verbal memory in patients with multiple sclerosis (MS), according to data from a pilot study presented at the 140th Annual Meeting of the American Neurological Association. The stimulation may not consistently improve working memory, however, contrary to the researchers’ expectations.

Cognitive dysfunction, including working memory deficits, and fatigue are common and debilitating symptoms of MS, said Tracy D. Vannorsdall, PhD, Assistant Professor of Neurology and Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine in Baltimore. Prior studies have shown that tDCS enhances working memory in healthy adults. To see if tDCS might improve working memory in patients with MS, Dr. Vannorsdall and her research colleagues conducted a sham-controlled, single-blind crossover study.

A Sham Stimulation Control

The investigators recruited five patients with secondary progressive MS from the Johns Hopkins MS Center. All participants were right-handed native English speakers, and three of the participants were women. Participants were between the ages of 42 and 57, with an average age of 50. They had a mean estimated IQ of 119 and a mean 18.4 years of schooling.

Participants completed cognitive testing before and after receiving 2 mA of anodal or sham stimulation to the left dorsolateral prefrontal cortex for 30 minutes once per day for five consecutive days. Investigators administered the current using a NeuroConn Stimulator Plus. For the sham stimulation, researchers increased the anodal current to 2 mA and decreased it to 0 mA over 30 seconds. After a four-week washout period, participants repeated the study procedures under the stimulation condition to which they had not been assigned originally.

Evaluating Cognition

Participants completed the Minimal Assessment of Cognitive Functioning in MS, a seven-subtest battery that assesses verbal learning and memory, visuospatial learning and memory, working memory, processing speed, verbal fluency, executive functioning, and perceptual accuracy. Participants also completed self-report measures of mood and fatigue and responded to a mental and physical side effects questionnaire. The researchers performed two-tailed paired-samples t-tests to compare changes in scores across anodal and sham conditions.

No adverse events occurred. Depression scale ratings did not significantly change during tDCS, compared with sham stimulation.

Fatigue Severity Scale

Participants’ scores on the Fatigue Severity Scale increased by 7 points over the course of five days of sham stimulation, compared with a decrease of 4.6 points over the course of anodal stimulation.

In addition, researchers observed a trend toward improved verbal immediate recall under the anodal condition, compared with sham stimulation. Anodal stimulation also was associated with better performance across most cognitive tests, but the differences were not significant. The study was underpowered to detect whether reduced fatigue contributed to the improvements in cognition. “These preliminary findings suggest that tDCS may ameliorate fatigue and cognitive dysfunction in secondary progressive MS,” concluded the researchers. Future studies will investigate the mechanism of these effects.

—Jake Remaly

Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online ahead of print October 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for inflammatory bowel disease and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between inflammatory bowel disease and demyelinating disease.

Researchers examined the issue by analyzing data from nationwide Danish health registries for patients with inflammatory bowel disease and medication exposure. They identified 4,504 patients treated during a 14-year period who had inflammatory bowel disease and took anti-TNF agents, and 16,429 patients with inflammatory bowel disease matched for sex, age, and disease duration who did not take the medications, according to Nynne Nyboe Andersen, MD, a doctoral student in the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, and her associates.

Eleven patients in the group exposed to medication had central demyelinating events. Two patients had multiple sclerosis, five patients had optic neuritis, and four patients had other central demyelinating disease. Medication-exposed patients had 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events. Five patients had multiple sclerosis, six patients had optic neuritis, one patient had transverse myelitis, and five patients had other central demyelinating disease. The unexposed group had 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, according to the investigators. These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers. “If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” said Dr. Nyboe Andersen.

—Mary Ann Moon

Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online ahead of print October 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for inflammatory bowel disease and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between inflammatory bowel disease and demyelinating disease.

Researchers examined the issue by analyzing data from nationwide Danish health registries for patients with inflammatory bowel disease and medication exposure. They identified 4,504 patients treated during a 14-year period who had inflammatory bowel disease and took anti-TNF agents, and 16,429 patients with inflammatory bowel disease matched for sex, age, and disease duration who did not take the medications, according to Nynne Nyboe Andersen, MD, a doctoral student in the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, and her associates.

Eleven patients in the group exposed to medication had central demyelinating events. Two patients had multiple sclerosis, five patients had optic neuritis, and four patients had other central demyelinating disease. Medication-exposed patients had 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events. Five patients had multiple sclerosis, six patients had optic neuritis, one patient had transverse myelitis, and five patients had other central demyelinating disease. The unexposed group had 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, according to the investigators. These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers. “If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” said Dr. Nyboe Andersen.

—Mary Ann Moon

Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online ahead of print October 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for inflammatory bowel disease and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between inflammatory bowel disease and demyelinating disease.

Researchers examined the issue by analyzing data from nationwide Danish health registries for patients with inflammatory bowel disease and medication exposure. They identified 4,504 patients treated during a 14-year period who had inflammatory bowel disease and took anti-TNF agents, and 16,429 patients with inflammatory bowel disease matched for sex, age, and disease duration who did not take the medications, according to Nynne Nyboe Andersen, MD, a doctoral student in the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, and her associates.

Eleven patients in the group exposed to medication had central demyelinating events. Two patients had multiple sclerosis, five patients had optic neuritis, and four patients had other central demyelinating disease. Medication-exposed patients had 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events. Five patients had multiple sclerosis, six patients had optic neuritis, one patient had transverse myelitis, and five patients had other central demyelinating disease. The unexposed group had 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, according to the investigators. These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers. “If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” said Dr. Nyboe Andersen.

—Mary Ann Moon

As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability, according to a study of 794 patients with relapsing-remitting multiple sclerosis aged 18 to 55 years. Researchers found:

• Estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo, confirming study sensitivity.

• For gadolinium-enhancing, the estimated ratio of generic drug to brand drug was within the predefined equivalence margin.

• The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups.

Citation: Cohen J, Belova A, Selmaj K, et al. Equivalence of generic glatiramer acetate in multiple sclerosis. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2154.

As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability, according to a study of 794 patients with relapsing-remitting multiple sclerosis aged 18 to 55 years. Researchers found:

• Estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo, confirming study sensitivity.

• For gadolinium-enhancing, the estimated ratio of generic drug to brand drug was within the predefined equivalence margin.

• The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups.

Citation: Cohen J, Belova A, Selmaj K, et al. Equivalence of generic glatiramer acetate in multiple sclerosis. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2154.

As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability, according to a study of 794 patients with relapsing-remitting multiple sclerosis aged 18 to 55 years. Researchers found:

• Estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo, confirming study sensitivity.

• For gadolinium-enhancing, the estimated ratio of generic drug to brand drug was within the predefined equivalence margin.

• The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups.

Citation: Cohen J, Belova A, Selmaj K, et al. Equivalence of generic glatiramer acetate in multiple sclerosis. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2154.

Among patients with multiple sclerosis (MS) treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI, according to a study of 1,482 patients with relapsing-remitting MS treated with interferon beta-1b. Researchers found:

• Average 25(OH)D levels were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI.

• A 50.0-nmol/L increase in serum 25(OH)D levels was associated with a 31% lower rate of new lesions.

• The lowest rate of new lesions was seen in patients with 25(OH)D levels greater than 100.0 nmol/L.

• No significant associations were seen between 25(OH)D levels and change in brain volume, relapse rates, or Expanded Disability Status Scale score.

• Results were consistent following adjustments for DRB1*15 or vitamin D-binding protein status.

Citation: Fitzgerald KC, Menger KL, Kӧchert K, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2742.

Among patients with multiple sclerosis (MS) treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI, according to a study of 1,482 patients with relapsing-remitting MS treated with interferon beta-1b. Researchers found:

• Average 25(OH)D levels were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI.

• A 50.0-nmol/L increase in serum 25(OH)D levels was associated with a 31% lower rate of new lesions.

• The lowest rate of new lesions was seen in patients with 25(OH)D levels greater than 100.0 nmol/L.

• No significant associations were seen between 25(OH)D levels and change in brain volume, relapse rates, or Expanded Disability Status Scale score.

• Results were consistent following adjustments for DRB1*15 or vitamin D-binding protein status.

Citation: Fitzgerald KC, Menger KL, Kӧchert K, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2742.

Among patients with multiple sclerosis (MS) treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI, according to a study of 1,482 patients with relapsing-remitting MS treated with interferon beta-1b. Researchers found:

• Average 25(OH)D levels were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI.

• A 50.0-nmol/L increase in serum 25(OH)D levels was associated with a 31% lower rate of new lesions.

• The lowest rate of new lesions was seen in patients with 25(OH)D levels greater than 100.0 nmol/L.

• No significant associations were seen between 25(OH)D levels and change in brain volume, relapse rates, or Expanded Disability Status Scale score.

• Results were consistent following adjustments for DRB1*15 or vitamin D-binding protein status.

Citation: Fitzgerald KC, Menger KL, Kӧchert K, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2742.

BARCELONA—In addition to its neuroprotective effect on the peripapillary retinal nerve fiber layer, sodium channel blockade with phenytoin also appears to prevent degeneration of the macular ganglion cell complex after acute optic neuritis, according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Rhian E. Raftopoulos, MbChb, of University College London, and colleagues previously reported in a phase II trial that sodium channel blockade with phenytoin is neuroprotective in acute optic neuritis. The primary outcome measurements were the thickness of the peripapillary retinal nerve fiber layer and macular volume, measured using optical coherence tomography (OCT).

In the present study, the researchers sought to determine whether this neuroprotective effect is selective for particular anatomical layers of the retina. They enrolled patients with acute optic neuritis and randomized them within two weeks of symptom onset to receive phenytoin or placebo for three months. Spectral domain fast macular and papillomacular bundle (PMB) OCT scans were performed at baseline and after six months. Masked automated retinal layer segmentation was performed to obtain average thickness measures of retinal nerve fiber layer, ganglion cell and inner plexiform layer (GC/IPL), and the composite ganglion cell complex. The ganglion cell complex (GCC) encompassed the retinal nerve fiber layer plus GC/IPL. Active versus placebo differences in mean six-month affected eye retinal nerve fiber layer, GC/IPL, and GCC were calculated from macular (n=60) and PMB (n=48) scans, adjusted for the corresponding baseline measurements in the unaffected eye.

At baseline, the mean thicknesses of the retinal nerve fiber layer, GC/IPL, and GCC were similar in the active and placebo groups in the macula and papillomacular bundle. In the intention to treat comparison, mean adjusted affected eye macular retinal nerve fiber layer thickness at six months was 4.67 μm greater in the active group (a 42% treatment effect). Mean adjusted macular GCC thickness was 5.63 μm greater in the active group (a 28% treatment effect). Treatment had no significant effect on macular GC/IPL when measured alone.

In the papillomacular bundle, mean adjusted retinal nerve fiber layer thickness was 2.49 μm greater in the active group at six months, mean GC/IPL thickness 2.79 μm greater, and mean GCC thickness 5.41 μm greater.

BARCELONA—In addition to its neuroprotective effect on the peripapillary retinal nerve fiber layer, sodium channel blockade with phenytoin also appears to prevent degeneration of the macular ganglion cell complex after acute optic neuritis, according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Rhian E. Raftopoulos, MbChb, of University College London, and colleagues previously reported in a phase II trial that sodium channel blockade with phenytoin is neuroprotective in acute optic neuritis. The primary outcome measurements were the thickness of the peripapillary retinal nerve fiber layer and macular volume, measured using optical coherence tomography (OCT).

In the present study, the researchers sought to determine whether this neuroprotective effect is selective for particular anatomical layers of the retina. They enrolled patients with acute optic neuritis and randomized them within two weeks of symptom onset to receive phenytoin or placebo for three months. Spectral domain fast macular and papillomacular bundle (PMB) OCT scans were performed at baseline and after six months. Masked automated retinal layer segmentation was performed to obtain average thickness measures of retinal nerve fiber layer, ganglion cell and inner plexiform layer (GC/IPL), and the composite ganglion cell complex. The ganglion cell complex (GCC) encompassed the retinal nerve fiber layer plus GC/IPL. Active versus placebo differences in mean six-month affected eye retinal nerve fiber layer, GC/IPL, and GCC were calculated from macular (n=60) and PMB (n=48) scans, adjusted for the corresponding baseline measurements in the unaffected eye.

At baseline, the mean thicknesses of the retinal nerve fiber layer, GC/IPL, and GCC were similar in the active and placebo groups in the macula and papillomacular bundle. In the intention to treat comparison, mean adjusted affected eye macular retinal nerve fiber layer thickness at six months was 4.67 μm greater in the active group (a 42% treatment effect). Mean adjusted macular GCC thickness was 5.63 μm greater in the active group (a 28% treatment effect). Treatment had no significant effect on macular GC/IPL when measured alone.

In the papillomacular bundle, mean adjusted retinal nerve fiber layer thickness was 2.49 μm greater in the active group at six months, mean GC/IPL thickness 2.79 μm greater, and mean GCC thickness 5.41 μm greater.

BARCELONA—In addition to its neuroprotective effect on the peripapillary retinal nerve fiber layer, sodium channel blockade with phenytoin also appears to prevent degeneration of the macular ganglion cell complex after acute optic neuritis, according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Rhian E. Raftopoulos, MbChb, of University College London, and colleagues previously reported in a phase II trial that sodium channel blockade with phenytoin is neuroprotective in acute optic neuritis. The primary outcome measurements were the thickness of the peripapillary retinal nerve fiber layer and macular volume, measured using optical coherence tomography (OCT).

In the present study, the researchers sought to determine whether this neuroprotective effect is selective for particular anatomical layers of the retina. They enrolled patients with acute optic neuritis and randomized them within two weeks of symptom onset to receive phenytoin or placebo for three months. Spectral domain fast macular and papillomacular bundle (PMB) OCT scans were performed at baseline and after six months. Masked automated retinal layer segmentation was performed to obtain average thickness measures of retinal nerve fiber layer, ganglion cell and inner plexiform layer (GC/IPL), and the composite ganglion cell complex. The ganglion cell complex (GCC) encompassed the retinal nerve fiber layer plus GC/IPL. Active versus placebo differences in mean six-month affected eye retinal nerve fiber layer, GC/IPL, and GCC were calculated from macular (n=60) and PMB (n=48) scans, adjusted for the corresponding baseline measurements in the unaffected eye.

At baseline, the mean thicknesses of the retinal nerve fiber layer, GC/IPL, and GCC were similar in the active and placebo groups in the macula and papillomacular bundle. In the intention to treat comparison, mean adjusted affected eye macular retinal nerve fiber layer thickness at six months was 4.67 μm greater in the active group (a 42% treatment effect). Mean adjusted macular GCC thickness was 5.63 μm greater in the active group (a 28% treatment effect). Treatment had no significant effect on macular GC/IPL when measured alone.

In the papillomacular bundle, mean adjusted retinal nerve fiber layer thickness was 2.49 μm greater in the active group at six months, mean GC/IPL thickness 2.79 μm greater, and mean GCC thickness 5.41 μm greater.

BARCELONA—The anti-JCV antibody index and L-selectin (CD62L) have merit for risk stratification and share a potential biological relationship with implications for general progressive multifocal leukoencephalopathy (PML) etiology, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). “A risk algorithm incorporating both biomarkers could strongly reduce PML incidence,” said Nicholas Schwab, PhD, of the Department of Neurology at the University of Münster in Germany.

Natalizumab treatment is associated with PML development, with more than 541 cases as of March 3, 2015. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for categorical risk stratification, but PML incidence continues to rise steadily. Anti-JCV antibody index and CD62L have previously been proposed as additional risk stratification parameters. Dr. Schwab and his research colleagues aimed at verifying and integrating both parameters into one applicable algorithm for risk stratification.

The research team gathered international cohorts of patients with multiple sclerosis who were treated with natalizumab. The participants were assessed for JCV index (1,921 control patients and nine pre-PML patients) and CD62L (1,257 control patients and 17 pre-PML patients).

Low CD62L in natalizumab-treated patients was retrospectively confirmed and prospectively validated as a biomarker for PML risk. The risk factor “CD62L low” increased a patient’s relative risk 55-fold. Validation efforts established an 86% sensitivity and 91% specificity for CD62L and 100% sensitivity and 59% specificity for JCV index as predictors of PML.

Low CD62L values were also found in various other PML associations and stages (ie, lupus, lymphopenia, HIV, acute natalizumab-PML). CD62L values correlated with JCV serostatus, so the lower the CD62L value of a patient was, the higher the probability that they were JCV positive. The researchers ultimately found that 26 out of 27 (96%) patients with low CD62L were JCV positive. Additionally, CD62L values negatively correlated with JCV index values.

“The combined use of JCV serology and CD62L level found 2% of patients studied to be at highest risk,” Dr. Schwab reported. “Adherence to the risk-stratification algorithm might prevent up to or over 85% of PML cases,” he said.

BARCELONA—The anti-JCV antibody index and L-selectin (CD62L) have merit for risk stratification and share a potential biological relationship with implications for general progressive multifocal leukoencephalopathy (PML) etiology, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). “A risk algorithm incorporating both biomarkers could strongly reduce PML incidence,” said Nicholas Schwab, PhD, of the Department of Neurology at the University of Münster in Germany.

Natalizumab treatment is associated with PML development, with more than 541 cases as of March 3, 2015. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for categorical risk stratification, but PML incidence continues to rise steadily. Anti-JCV antibody index and CD62L have previously been proposed as additional risk stratification parameters. Dr. Schwab and his research colleagues aimed at verifying and integrating both parameters into one applicable algorithm for risk stratification.

The research team gathered international cohorts of patients with multiple sclerosis who were treated with natalizumab. The participants were assessed for JCV index (1,921 control patients and nine pre-PML patients) and CD62L (1,257 control patients and 17 pre-PML patients).

Low CD62L in natalizumab-treated patients was retrospectively confirmed and prospectively validated as a biomarker for PML risk. The risk factor “CD62L low” increased a patient’s relative risk 55-fold. Validation efforts established an 86% sensitivity and 91% specificity for CD62L and 100% sensitivity and 59% specificity for JCV index as predictors of PML.

Low CD62L values were also found in various other PML associations and stages (ie, lupus, lymphopenia, HIV, acute natalizumab-PML). CD62L values correlated with JCV serostatus, so the lower the CD62L value of a patient was, the higher the probability that they were JCV positive. The researchers ultimately found that 26 out of 27 (96%) patients with low CD62L were JCV positive. Additionally, CD62L values negatively correlated with JCV index values.

“The combined use of JCV serology and CD62L level found 2% of patients studied to be at highest risk,” Dr. Schwab reported. “Adherence to the risk-stratification algorithm might prevent up to or over 85% of PML cases,” he said.

BARCELONA—The anti-JCV antibody index and L-selectin (CD62L) have merit for risk stratification and share a potential biological relationship with implications for general progressive multifocal leukoencephalopathy (PML) etiology, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). “A risk algorithm incorporating both biomarkers could strongly reduce PML incidence,” said Nicholas Schwab, PhD, of the Department of Neurology at the University of Münster in Germany.

Natalizumab treatment is associated with PML development, with more than 541 cases as of March 3, 2015. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for categorical risk stratification, but PML incidence continues to rise steadily. Anti-JCV antibody index and CD62L have previously been proposed as additional risk stratification parameters. Dr. Schwab and his research colleagues aimed at verifying and integrating both parameters into one applicable algorithm for risk stratification.

The research team gathered international cohorts of patients with multiple sclerosis who were treated with natalizumab. The participants were assessed for JCV index (1,921 control patients and nine pre-PML patients) and CD62L (1,257 control patients and 17 pre-PML patients).

Low CD62L in natalizumab-treated patients was retrospectively confirmed and prospectively validated as a biomarker for PML risk. The risk factor “CD62L low” increased a patient’s relative risk 55-fold. Validation efforts established an 86% sensitivity and 91% specificity for CD62L and 100% sensitivity and 59% specificity for JCV index as predictors of PML.

Low CD62L values were also found in various other PML associations and stages (ie, lupus, lymphopenia, HIV, acute natalizumab-PML). CD62L values correlated with JCV serostatus, so the lower the CD62L value of a patient was, the higher the probability that they were JCV positive. The researchers ultimately found that 26 out of 27 (96%) patients with low CD62L were JCV positive. Additionally, CD62L values negatively correlated with JCV index values.

“The combined use of JCV serology and CD62L level found 2% of patients studied to be at highest risk,” Dr. Schwab reported. “Adherence to the risk-stratification algorithm might prevent up to or over 85% of PML cases,” he said.

BARCELONA—When added to other antispasticity treatments, an oromucosal spray containing approximately equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) provides effective symptomatic relief of treatment-resistant MS spasticity, according to a study presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The drug also is well tolerated in clinical practice.

“The results for spasticity evolution and tolerability in this patient cohort … compare favorably with results reported in randomized controlled trials and other observational studies of THC:CBD oromucosal spray,” said Maria Trojano, MD, Director of the Department of Basic Medical Sciences, Neurosciences, and Sensory Organs at the University of Bari in Italy, and her colleagues.

Randomized controlled trials indicate that THC:CBD oromucosal spray significantly reduces MS spasticity, compared with placebo, and does not raise significant tolerability concerns. German investigators initiated the prospective, noninterventional Mobility Improvement (MOVE) 2 study to examine the spray’s efficacy and tolerability in everyday clinical practice. Patients received treatment with the spray according to its approved use label in the outpatient setting in Europe.

Several Italian centers joined the MOVE 2 study, and Italy became the first country to reach the recruitment target of 300 or more patients for a preplanned interim analysis. Specialist MS centers in Italy are collecting data on MS spasticity from electronic case record forms and patients’ diaries at baseline and after one month (ie, Visit 1) and three months (ie, Visit 3) of treatment with THC:CBD oromucosal spray. The researchers are measuring effectiveness by rates of treatment continuation and changes from baseline in scores on the spasticity numerical rating scale (NRS) and modified Ashworth scale. The researchers also are inquiring about tolerability and adverse events.

In all, 322 patients (58.3% female, mean age 51.1) with treatment-resistant MS spasticity were recruited at 34 Italian MS centers. Baseline antispasticity medicines included baclofen (71.1%), gabapentin–pregabalin (10.9%), benzodiazepines (6.8%), and tizanidine (5.9%). About half of patients were receiving concomitant physiotherapy.

Mean doses of the spray were 6.1 sprays/day at Visit 1 and 5.1 sprays/day at Visit 3. At Visit 1, 82.9% of patients had an initial response to the THC:CBD oromucosal spray (ie, an improvement from baseline NRS score of at least 20%) and continued with treatment. At Visit 3, 24.6% of patients with available data had a clinically relevant response to the spray (ie, improvement from baseline NRS score of at least 30%) and continued with treatment. An additional 53.2% of patients continued to use the spray after Visit 3 although their improvement on the spasticity NRS was less than 30%.

Mean spasticity NRS score was 6.8 at baseline. The score decreased to 5.5 in patients with available data at Visit 3, representing a significant 19.1% improvement. Mean modified Ashworth scale score was 2.6 at baseline. The score decreased to 2.2 at Visit 1 and was 2.3 in patients with available data at Visit 3.

Rates of treatment discontinuation were 8.7% at Visit 1 and 22.2% at Visit 3. The main reasons for treatment discontinuation were lack of effectiveness (42%), lack of tolerability (42%), and pregnancy or other reasons (16%). Approximately 13% of patients reported at least one adverse event. All nonserious adverse events were mild to moderate. Adverse events with an incidence of 1% or greater included dizziness, confusion, nausea, and somnolence. Two serious adverse events, mental impairment and suicidal ideation, were considered as possibly related to treatment. One death was considered unrelated to treatment.

BARCELONA—When added to other antispasticity treatments, an oromucosal spray containing approximately equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) provides effective symptomatic relief of treatment-resistant MS spasticity, according to a study presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The drug also is well tolerated in clinical practice.

“The results for spasticity evolution and tolerability in this patient cohort … compare favorably with results reported in randomized controlled trials and other observational studies of THC:CBD oromucosal spray,” said Maria Trojano, MD, Director of the Department of Basic Medical Sciences, Neurosciences, and Sensory Organs at the University of Bari in Italy, and her colleagues.

Randomized controlled trials indicate that THC:CBD oromucosal spray significantly reduces MS spasticity, compared with placebo, and does not raise significant tolerability concerns. German investigators initiated the prospective, noninterventional Mobility Improvement (MOVE) 2 study to examine the spray’s efficacy and tolerability in everyday clinical practice. Patients received treatment with the spray according to its approved use label in the outpatient setting in Europe.

Several Italian centers joined the MOVE 2 study, and Italy became the first country to reach the recruitment target of 300 or more patients for a preplanned interim analysis. Specialist MS centers in Italy are collecting data on MS spasticity from electronic case record forms and patients’ diaries at baseline and after one month (ie, Visit 1) and three months (ie, Visit 3) of treatment with THC:CBD oromucosal spray. The researchers are measuring effectiveness by rates of treatment continuation and changes from baseline in scores on the spasticity numerical rating scale (NRS) and modified Ashworth scale. The researchers also are inquiring about tolerability and adverse events.

In all, 322 patients (58.3% female, mean age 51.1) with treatment-resistant MS spasticity were recruited at 34 Italian MS centers. Baseline antispasticity medicines included baclofen (71.1%), gabapentin–pregabalin (10.9%), benzodiazepines (6.8%), and tizanidine (5.9%). About half of patients were receiving concomitant physiotherapy.

Mean doses of the spray were 6.1 sprays/day at Visit 1 and 5.1 sprays/day at Visit 3. At Visit 1, 82.9% of patients had an initial response to the THC:CBD oromucosal spray (ie, an improvement from baseline NRS score of at least 20%) and continued with treatment. At Visit 3, 24.6% of patients with available data had a clinically relevant response to the spray (ie, improvement from baseline NRS score of at least 30%) and continued with treatment. An additional 53.2% of patients continued to use the spray after Visit 3 although their improvement on the spasticity NRS was less than 30%.

Mean spasticity NRS score was 6.8 at baseline. The score decreased to 5.5 in patients with available data at Visit 3, representing a significant 19.1% improvement. Mean modified Ashworth scale score was 2.6 at baseline. The score decreased to 2.2 at Visit 1 and was 2.3 in patients with available data at Visit 3.

Rates of treatment discontinuation were 8.7% at Visit 1 and 22.2% at Visit 3. The main reasons for treatment discontinuation were lack of effectiveness (42%), lack of tolerability (42%), and pregnancy or other reasons (16%). Approximately 13% of patients reported at least one adverse event. All nonserious adverse events were mild to moderate. Adverse events with an incidence of 1% or greater included dizziness, confusion, nausea, and somnolence. Two serious adverse events, mental impairment and suicidal ideation, were considered as possibly related to treatment. One death was considered unrelated to treatment.

BARCELONA—When added to other antispasticity treatments, an oromucosal spray containing approximately equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) provides effective symptomatic relief of treatment-resistant MS spasticity, according to a study presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The drug also is well tolerated in clinical practice.

“The results for spasticity evolution and tolerability in this patient cohort … compare favorably with results reported in randomized controlled trials and other observational studies of THC:CBD oromucosal spray,” said Maria Trojano, MD, Director of the Department of Basic Medical Sciences, Neurosciences, and Sensory Organs at the University of Bari in Italy, and her colleagues.

Randomized controlled trials indicate that THC:CBD oromucosal spray significantly reduces MS spasticity, compared with placebo, and does not raise significant tolerability concerns. German investigators initiated the prospective, noninterventional Mobility Improvement (MOVE) 2 study to examine the spray’s efficacy and tolerability in everyday clinical practice. Patients received treatment with the spray according to its approved use label in the outpatient setting in Europe.

Several Italian centers joined the MOVE 2 study, and Italy became the first country to reach the recruitment target of 300 or more patients for a preplanned interim analysis. Specialist MS centers in Italy are collecting data on MS spasticity from electronic case record forms and patients’ diaries at baseline and after one month (ie, Visit 1) and three months (ie, Visit 3) of treatment with THC:CBD oromucosal spray. The researchers are measuring effectiveness by rates of treatment continuation and changes from baseline in scores on the spasticity numerical rating scale (NRS) and modified Ashworth scale. The researchers also are inquiring about tolerability and adverse events.

In all, 322 patients (58.3% female, mean age 51.1) with treatment-resistant MS spasticity were recruited at 34 Italian MS centers. Baseline antispasticity medicines included baclofen (71.1%), gabapentin–pregabalin (10.9%), benzodiazepines (6.8%), and tizanidine (5.9%). About half of patients were receiving concomitant physiotherapy.

Mean doses of the spray were 6.1 sprays/day at Visit 1 and 5.1 sprays/day at Visit 3. At Visit 1, 82.9% of patients had an initial response to the THC:CBD oromucosal spray (ie, an improvement from baseline NRS score of at least 20%) and continued with treatment. At Visit 3, 24.6% of patients with available data had a clinically relevant response to the spray (ie, improvement from baseline NRS score of at least 30%) and continued with treatment. An additional 53.2% of patients continued to use the spray after Visit 3 although their improvement on the spasticity NRS was less than 30%.

Mean spasticity NRS score was 6.8 at baseline. The score decreased to 5.5 in patients with available data at Visit 3, representing a significant 19.1% improvement. Mean modified Ashworth scale score was 2.6 at baseline. The score decreased to 2.2 at Visit 1 and was 2.3 in patients with available data at Visit 3.

Rates of treatment discontinuation were 8.7% at Visit 1 and 22.2% at Visit 3. The main reasons for treatment discontinuation were lack of effectiveness (42%), lack of tolerability (42%), and pregnancy or other reasons (16%). Approximately 13% of patients reported at least one adverse event. All nonserious adverse events were mild to moderate. Adverse events with an incidence of 1% or greater included dizziness, confusion, nausea, and somnolence. Two serious adverse events, mental impairment and suicidal ideation, were considered as possibly related to treatment. One death was considered unrelated to treatment.