CHICAGO – New draft guidelines for treating juvenile idiopathic arthritis (JIA) written by experts assembled by the American College of Rheumatology “formalize inactive disease as the goal of treatment,” Timothy G. Beukelman, MD, said at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/MDedge News

“We defined low disease activity as patients with a single active joint, and the goal is to have zero active joints. Low disease activity should not be tolerated” in patients with JIA, said Dr. Beukelman, a pediatric rheumatologist at the University of Alabama at Birmingham and a member of the guideline-writing committee. “Until now, treating these patients to zero active joints has not been recommended. But clinically inactive disease is a realistic target for a majority of JIA patients,” he said in an interview.

Despite this shift in the recommended treatment goal, the writing panel was forced to rely largely on their expertise rather than reported evidence. The recommendation by the committee to escalate therapy in patients with low disease activity was “conditional,” with a level of evidence deemed “very low,” Dr. Beukelman said during a talk in which he cited selected highlights from the committee’s full list of 39 recommendations.

The paucity of evidence reflected the status of many of the recommendations: 31 of the 39 recommendations were conditional, which means that the desirable effects from treatment “probably” outweigh the undesirable effects, and they may not apply to some patients. The writing panel pegged 22 of their recommendations as having a very low evidence backing and another 13 recommendations had low evidence. The JIA committee believed that none of its recommendations had strong evidence to back them up.

Dr. Beukelman defended writing recommendations despite this absence of evidence. “We should continue to write conditional recommendations when we don’t have the evidence. These recommendations had approval from at least 70% of the writing group, a diverse committee of experts. They should not be taken lightly just because they are conditional.”

Dr. Beukelman also stressed that he was presenting draft recommendations that still awaited approval from the ACR and the Arthritis Foundation, which collaborated with the ACR on this project. Once adopted, the new document would revise the existing management recommendations that the ACR approved in 2011 (Arthritis Rheum. 2011 Apr;63[4]:465-82).

The recommendations Dr. Beukelman outlined focused on treatment of polyarthritis, sacroiliitis, and enthesitis, and Dr. Beukelman devoted the most time to detailing some of the statements on polyarthritis. The panel conditionally recommended methotrexate over leflunomide (Arava) or sulfasalazine with moderate or very low evidence and said that subcutaneous methotrexate was conditionally preferred over oral dosing for reasons of both better efficacy and tolerability. Combination of a biologic agent with a nonbiologic received a conditional recommendation over biologic monotherapy, with moderate to very low evidence, but with a strong recommendation for this combined approach when using infliximab (Remicade), based on moderate evidence.

Another strong recommendation was to avoid treating patients with a chronic course of a low-dose, systemic glucocorticoid, based on a very low level of evidence. A brief course, less than 3 months, of an oral glucocorticoid received conditional recommendation for patients with moderate or high disease activity, based on very low evidence, but also received a conditional negative recommendation for patients with low disease activity, also based on very low evidence.

Initial therapy with a disease-modifying antirheumatic drug (DMARD) instead of monotherapy with an NSAID received a strong recommendation, based on a moderate level of evidence, while initial therapy with a DMARD received conditional support over initial therapy with a biologic agent, based on low evidence.

The panel gave a conditional endorsement to the idea of switching from a tumor necrosis factor inhibitor (TNFi) to a different biologic drug class when patients remained with moderate or high disease activity, based on a very low level of evidence.

Regarding sacroiliitis, the panel strongly recommended starting a TNFi in patients with active sacroiliitis despite NSAID treatment, based on low evidence, and the committee strongly recommended against starting methotrexate treatment in these patients, based on very low evidence. For treating active enthesitis despite NSAID treatment, the panel conditionally recommended adding a TNFi over treatment with methotrexate or sulfasalazine, based on a low level of evidence. Dr. Beukelman highlighted that the new recommendations placed increased emphasis on treating sacroiliitis, compared with the 2011 statement, and that the new recommendations dealt with treating enthesitis for the first time.

Dr. Beukelman has been a consultant to Bristol-Myers Squibb, Novartis, Sobi, and UCB.

[email protected]

CHICAGO – New draft guidelines for treating juvenile idiopathic arthritis (JIA) written by experts assembled by the American College of Rheumatology “formalize inactive disease as the goal of treatment,” Timothy G. Beukelman, MD, said at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/MDedge News

“We defined low disease activity as patients with a single active joint, and the goal is to have zero active joints. Low disease activity should not be tolerated” in patients with JIA, said Dr. Beukelman, a pediatric rheumatologist at the University of Alabama at Birmingham and a member of the guideline-writing committee. “Until now, treating these patients to zero active joints has not been recommended. But clinically inactive disease is a realistic target for a majority of JIA patients,” he said in an interview.

Despite this shift in the recommended treatment goal, the writing panel was forced to rely largely on their expertise rather than reported evidence. The recommendation by the committee to escalate therapy in patients with low disease activity was “conditional,” with a level of evidence deemed “very low,” Dr. Beukelman said during a talk in which he cited selected highlights from the committee’s full list of 39 recommendations.

The paucity of evidence reflected the status of many of the recommendations: 31 of the 39 recommendations were conditional, which means that the desirable effects from treatment “probably” outweigh the undesirable effects, and they may not apply to some patients. The writing panel pegged 22 of their recommendations as having a very low evidence backing and another 13 recommendations had low evidence. The JIA committee believed that none of its recommendations had strong evidence to back them up.

Dr. Beukelman defended writing recommendations despite this absence of evidence. “We should continue to write conditional recommendations when we don’t have the evidence. These recommendations had approval from at least 70% of the writing group, a diverse committee of experts. They should not be taken lightly just because they are conditional.”

Dr. Beukelman also stressed that he was presenting draft recommendations that still awaited approval from the ACR and the Arthritis Foundation, which collaborated with the ACR on this project. Once adopted, the new document would revise the existing management recommendations that the ACR approved in 2011 (Arthritis Rheum. 2011 Apr;63[4]:465-82).

The recommendations Dr. Beukelman outlined focused on treatment of polyarthritis, sacroiliitis, and enthesitis, and Dr. Beukelman devoted the most time to detailing some of the statements on polyarthritis. The panel conditionally recommended methotrexate over leflunomide (Arava) or sulfasalazine with moderate or very low evidence and said that subcutaneous methotrexate was conditionally preferred over oral dosing for reasons of both better efficacy and tolerability. Combination of a biologic agent with a nonbiologic received a conditional recommendation over biologic monotherapy, with moderate to very low evidence, but with a strong recommendation for this combined approach when using infliximab (Remicade), based on moderate evidence.

Another strong recommendation was to avoid treating patients with a chronic course of a low-dose, systemic glucocorticoid, based on a very low level of evidence. A brief course, less than 3 months, of an oral glucocorticoid received conditional recommendation for patients with moderate or high disease activity, based on very low evidence, but also received a conditional negative recommendation for patients with low disease activity, also based on very low evidence.

Initial therapy with a disease-modifying antirheumatic drug (DMARD) instead of monotherapy with an NSAID received a strong recommendation, based on a moderate level of evidence, while initial therapy with a DMARD received conditional support over initial therapy with a biologic agent, based on low evidence.

The panel gave a conditional endorsement to the idea of switching from a tumor necrosis factor inhibitor (TNFi) to a different biologic drug class when patients remained with moderate or high disease activity, based on a very low level of evidence.

Regarding sacroiliitis, the panel strongly recommended starting a TNFi in patients with active sacroiliitis despite NSAID treatment, based on low evidence, and the committee strongly recommended against starting methotrexate treatment in these patients, based on very low evidence. For treating active enthesitis despite NSAID treatment, the panel conditionally recommended adding a TNFi over treatment with methotrexate or sulfasalazine, based on a low level of evidence. Dr. Beukelman highlighted that the new recommendations placed increased emphasis on treating sacroiliitis, compared with the 2011 statement, and that the new recommendations dealt with treating enthesitis for the first time.

Dr. Beukelman has been a consultant to Bristol-Myers Squibb, Novartis, Sobi, and UCB.

[email protected]

CHICAGO – New draft guidelines for treating juvenile idiopathic arthritis (JIA) written by experts assembled by the American College of Rheumatology “formalize inactive disease as the goal of treatment,” Timothy G. Beukelman, MD, said at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/MDedge News

“We defined low disease activity as patients with a single active joint, and the goal is to have zero active joints. Low disease activity should not be tolerated” in patients with JIA, said Dr. Beukelman, a pediatric rheumatologist at the University of Alabama at Birmingham and a member of the guideline-writing committee. “Until now, treating these patients to zero active joints has not been recommended. But clinically inactive disease is a realistic target for a majority of JIA patients,” he said in an interview.

Despite this shift in the recommended treatment goal, the writing panel was forced to rely largely on their expertise rather than reported evidence. The recommendation by the committee to escalate therapy in patients with low disease activity was “conditional,” with a level of evidence deemed “very low,” Dr. Beukelman said during a talk in which he cited selected highlights from the committee’s full list of 39 recommendations.

The paucity of evidence reflected the status of many of the recommendations: 31 of the 39 recommendations were conditional, which means that the desirable effects from treatment “probably” outweigh the undesirable effects, and they may not apply to some patients. The writing panel pegged 22 of their recommendations as having a very low evidence backing and another 13 recommendations had low evidence. The JIA committee believed that none of its recommendations had strong evidence to back them up.

Dr. Beukelman defended writing recommendations despite this absence of evidence. “We should continue to write conditional recommendations when we don’t have the evidence. These recommendations had approval from at least 70% of the writing group, a diverse committee of experts. They should not be taken lightly just because they are conditional.”

Dr. Beukelman also stressed that he was presenting draft recommendations that still awaited approval from the ACR and the Arthritis Foundation, which collaborated with the ACR on this project. Once adopted, the new document would revise the existing management recommendations that the ACR approved in 2011 (Arthritis Rheum. 2011 Apr;63[4]:465-82).

The recommendations Dr. Beukelman outlined focused on treatment of polyarthritis, sacroiliitis, and enthesitis, and Dr. Beukelman devoted the most time to detailing some of the statements on polyarthritis. The panel conditionally recommended methotrexate over leflunomide (Arava) or sulfasalazine with moderate or very low evidence and said that subcutaneous methotrexate was conditionally preferred over oral dosing for reasons of both better efficacy and tolerability. Combination of a biologic agent with a nonbiologic received a conditional recommendation over biologic monotherapy, with moderate to very low evidence, but with a strong recommendation for this combined approach when using infliximab (Remicade), based on moderate evidence.

Another strong recommendation was to avoid treating patients with a chronic course of a low-dose, systemic glucocorticoid, based on a very low level of evidence. A brief course, less than 3 months, of an oral glucocorticoid received conditional recommendation for patients with moderate or high disease activity, based on very low evidence, but also received a conditional negative recommendation for patients with low disease activity, also based on very low evidence.

Initial therapy with a disease-modifying antirheumatic drug (DMARD) instead of monotherapy with an NSAID received a strong recommendation, based on a moderate level of evidence, while initial therapy with a DMARD received conditional support over initial therapy with a biologic agent, based on low evidence.

The panel gave a conditional endorsement to the idea of switching from a tumor necrosis factor inhibitor (TNFi) to a different biologic drug class when patients remained with moderate or high disease activity, based on a very low level of evidence.

Regarding sacroiliitis, the panel strongly recommended starting a TNFi in patients with active sacroiliitis despite NSAID treatment, based on low evidence, and the committee strongly recommended against starting methotrexate treatment in these patients, based on very low evidence. For treating active enthesitis despite NSAID treatment, the panel conditionally recommended adding a TNFi over treatment with methotrexate or sulfasalazine, based on a low level of evidence. Dr. Beukelman highlighted that the new recommendations placed increased emphasis on treating sacroiliitis, compared with the 2011 statement, and that the new recommendations dealt with treating enthesitis for the first time.

Dr. Beukelman has been a consultant to Bristol-Myers Squibb, Novartis, Sobi, and UCB.

[email protected]

Ob.Gyn. News welcomes Mark P. Trolice, MD, to the editorial advisory board.

Dr. Trolice is director of Fertility CARE: The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando, responsible for the medical education of ob.gyn. residents and medical students, as well as medical endocrinology fellows. He is past president of the Florida Society of Reproductive Endocrinology & Infertility (REI) and past division director of REI at Winnie Palmer Hospital, part of Orlando Health.

He is double board-certified in REI and ob.gyn., maintains annual recertification, and has been awarded the American Medical Association’s “Physicians’ Recognition Award” annually. He holds the unique distinction of being a fellow in all three American colleges: ob.gyn., surgeons, and endocrinology. His colleagues select him as a “Top Doctor in America” annually, one among the top 5% of doctors in the United States. In 2018, he was awarded the “Social Responsibility Award” by the National Polycystic Ovary Syndrome Association. For 10 years, his foundation, Fertile Dreams, organized seminars to increase fertility awareness and granted national scholarships for those unable to afford in vitro fertilization (IVF) treatment.

Dr. Trolice serves on committees for the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. He has conducted scientific studies with resultant numerous publications and been appointed a reviewer in many leading medical journals and textbooks. He has lectured at numerous physician and patient seminars around the country. In addition, he is interviewed regularly on TV news/talk shows, radio, podcasts, print/online magazines, and newspapers on reproductive health topics. In the fall of 2018, he launched a podcast entitled “Fertility Health” featuring discussions with national experts on pertinent infertility and reproductive medicine topics. His current book is on the infertility journey, to be published by Harvard Common Press in mid 2019.

Ob.Gyn. News welcomes Mark P. Trolice, MD, to the editorial advisory board.

Dr. Trolice is director of Fertility CARE: The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando, responsible for the medical education of ob.gyn. residents and medical students, as well as medical endocrinology fellows. He is past president of the Florida Society of Reproductive Endocrinology & Infertility (REI) and past division director of REI at Winnie Palmer Hospital, part of Orlando Health.

He is double board-certified in REI and ob.gyn., maintains annual recertification, and has been awarded the American Medical Association’s “Physicians’ Recognition Award” annually. He holds the unique distinction of being a fellow in all three American colleges: ob.gyn., surgeons, and endocrinology. His colleagues select him as a “Top Doctor in America” annually, one among the top 5% of doctors in the United States. In 2018, he was awarded the “Social Responsibility Award” by the National Polycystic Ovary Syndrome Association. For 10 years, his foundation, Fertile Dreams, organized seminars to increase fertility awareness and granted national scholarships for those unable to afford in vitro fertilization (IVF) treatment.

Dr. Trolice serves on committees for the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. He has conducted scientific studies with resultant numerous publications and been appointed a reviewer in many leading medical journals and textbooks. He has lectured at numerous physician and patient seminars around the country. In addition, he is interviewed regularly on TV news/talk shows, radio, podcasts, print/online magazines, and newspapers on reproductive health topics. In the fall of 2018, he launched a podcast entitled “Fertility Health” featuring discussions with national experts on pertinent infertility and reproductive medicine topics. His current book is on the infertility journey, to be published by Harvard Common Press in mid 2019.

Ob.Gyn. News welcomes Mark P. Trolice, MD, to the editorial advisory board.

Dr. Trolice is director of Fertility CARE: The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando, responsible for the medical education of ob.gyn. residents and medical students, as well as medical endocrinology fellows. He is past president of the Florida Society of Reproductive Endocrinology & Infertility (REI) and past division director of REI at Winnie Palmer Hospital, part of Orlando Health.

He is double board-certified in REI and ob.gyn., maintains annual recertification, and has been awarded the American Medical Association’s “Physicians’ Recognition Award” annually. He holds the unique distinction of being a fellow in all three American colleges: ob.gyn., surgeons, and endocrinology. His colleagues select him as a “Top Doctor in America” annually, one among the top 5% of doctors in the United States. In 2018, he was awarded the “Social Responsibility Award” by the National Polycystic Ovary Syndrome Association. For 10 years, his foundation, Fertile Dreams, organized seminars to increase fertility awareness and granted national scholarships for those unable to afford in vitro fertilization (IVF) treatment.

Dr. Trolice serves on committees for the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. He has conducted scientific studies with resultant numerous publications and been appointed a reviewer in many leading medical journals and textbooks. He has lectured at numerous physician and patient seminars around the country. In addition, he is interviewed regularly on TV news/talk shows, radio, podcasts, print/online magazines, and newspapers on reproductive health topics. In the fall of 2018, he launched a podcast entitled “Fertility Health” featuring discussions with national experts on pertinent infertility and reproductive medicine topics. His current book is on the infertility journey, to be published by Harvard Common Press in mid 2019.

Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.

Lynda Banzi/MDedge News

Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.

By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.

“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.

This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.


Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.

A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.

National Rosacea Society

By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.

Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”

However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.

Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
 

SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.

Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.

Lynda Banzi/MDedge News

Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.

By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.

“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.

This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.


Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.

A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.

National Rosacea Society

By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.

Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”

However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.

Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
 

SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.

Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.

Lynda Banzi/MDedge News

Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.

By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.

“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.

This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.


Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.

A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.

National Rosacea Society

By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.

Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”

However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.

Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
 

SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.

Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.

The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.

REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.

Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.

Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.

[email protected]

Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.

The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.

REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.

Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.

Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.

[email protected]

Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.

The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.

REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.

Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.

Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.

[email protected]

BARCELONA – Lithium and valproic acid are the treatments of choice for patients with bipolar disorder at increased risk for suicide, according to the findings of a large Finnish national study.

Bruce Jancin/MDedge News

“We found that – surprise, surprise – lithium and valproic acid had the lowest risk of anyone committing suicide on them. And funnily enough, some antidepressants seemed to be correlated with a higher risk of committing suicide,” Markku Lähteenvuo, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

However, he suspects that the correlation between antidepressant therapy and suicide in bipolar patients probably was caused by confounding by indication.

“I wouldn’t have as a take-home message that SSRI [selective serotonin reuptake inhibitor] antidepressants are bad for you; it’s probably rather that these are really bad cases, treatment gets initiated when someone gets worse, and the antidepressants just aren’t quick enough to really give an effect. It takes 3-4 weeks for an SSRI to really kick in, whereas mood stabilizers like lithium and valproic acid usually kick in almost immediately, within a couple of days to a week,” explained Dr. Lähteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland, in Kuopio.

He presented a study of all suicides among the 18,018 Finnish patients hospitalized for bipolar disorder nationwide during 1996-2012. Using prospective national databases to follow patients for a mean of 7.2 years, he and his coinvestigators were able to determine what medications they were on when they committed suicide and the likelihood they were actually taking their prescribed medications at the time.


In a multivariate proportional hazards analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, intervals of drug exposure and nonexposure, age, sex, and number of hospitalizations for suicidality within the prior 2 years, bipolar patients on lithium had a 67% lower risk of suicide than did those not on the drug. Those on valproic acid were 39% less likely to commit suicide than those not on that mood stabilizer. And bipolar patients on lithium were 42% less likely to die from suicide than those on valproic acid.

At the other extreme, patients on antidepressants were in aggregate 28% more likely to commit suicide than those who were not. This risk varied considerably according to the specific antidepressant: for example, escitalopram and mirtazapine were associated with 71% and 57% greater risks of suicide, respectively, than in patients not on those antidepressants, while patients on paroxetine, venlafaxine, or sertraline were not at increased risk.

Also, the use of sedatives was associated with a 52% greater likelihood of suicide, and benzodiazepines were linked to a 21% increase in risk. Again, as with antidepressants, these associations with increased risk of completed suicide could be attributable in part or in whole to confounding by indication, the psychiatrist noted. He and his colleagues are conducting further analyses examining that possibility.


Pending the outcome of that closer look, however, Dr. Lähteenvuo believes the study’s message to clinicians is clear: “The use of lithium is getting less and less common all the time because of side effects. That’s also true for valproic acid. Many bipolar patients are now prescribed only antidepressants, even though all the guidelines advise against it due to the risk of hypomania. We think that this is a bad trend and that lithium and valproic acid should be prescribed more. Also, as a safety precaution, anyone with bipolar disorder on antidepressants or benzodiazepines or sedatives should be followed especially closely for suicidal signals, because they could carry a really highly increased risk – up to 50% – due to the medication as well.”

He reported having no financial conflicts regarding the study, funded by the Finnish government.

Dr. Lähteenvuo also was first author of a recent study showing that among the various drugs prescribed for treatment of bipolar disorder, lithium was the clear winner for prevention of rehospitalization in the same national Finnish population of more than 18,000 bipolar patients (JAMA Psychiatry. 2018;75[4]:347-55). One expert named this among the top four studies of the year in the field of mood disorders.

[email protected]

BARCELONA – Lithium and valproic acid are the treatments of choice for patients with bipolar disorder at increased risk for suicide, according to the findings of a large Finnish national study.

Bruce Jancin/MDedge News

“We found that – surprise, surprise – lithium and valproic acid had the lowest risk of anyone committing suicide on them. And funnily enough, some antidepressants seemed to be correlated with a higher risk of committing suicide,” Markku Lähteenvuo, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

However, he suspects that the correlation between antidepressant therapy and suicide in bipolar patients probably was caused by confounding by indication.

“I wouldn’t have as a take-home message that SSRI [selective serotonin reuptake inhibitor] antidepressants are bad for you; it’s probably rather that these are really bad cases, treatment gets initiated when someone gets worse, and the antidepressants just aren’t quick enough to really give an effect. It takes 3-4 weeks for an SSRI to really kick in, whereas mood stabilizers like lithium and valproic acid usually kick in almost immediately, within a couple of days to a week,” explained Dr. Lähteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland, in Kuopio.

He presented a study of all suicides among the 18,018 Finnish patients hospitalized for bipolar disorder nationwide during 1996-2012. Using prospective national databases to follow patients for a mean of 7.2 years, he and his coinvestigators were able to determine what medications they were on when they committed suicide and the likelihood they were actually taking their prescribed medications at the time.


In a multivariate proportional hazards analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, intervals of drug exposure and nonexposure, age, sex, and number of hospitalizations for suicidality within the prior 2 years, bipolar patients on lithium had a 67% lower risk of suicide than did those not on the drug. Those on valproic acid were 39% less likely to commit suicide than those not on that mood stabilizer. And bipolar patients on lithium were 42% less likely to die from suicide than those on valproic acid.

At the other extreme, patients on antidepressants were in aggregate 28% more likely to commit suicide than those who were not. This risk varied considerably according to the specific antidepressant: for example, escitalopram and mirtazapine were associated with 71% and 57% greater risks of suicide, respectively, than in patients not on those antidepressants, while patients on paroxetine, venlafaxine, or sertraline were not at increased risk.

Also, the use of sedatives was associated with a 52% greater likelihood of suicide, and benzodiazepines were linked to a 21% increase in risk. Again, as with antidepressants, these associations with increased risk of completed suicide could be attributable in part or in whole to confounding by indication, the psychiatrist noted. He and his colleagues are conducting further analyses examining that possibility.


Pending the outcome of that closer look, however, Dr. Lähteenvuo believes the study’s message to clinicians is clear: “The use of lithium is getting less and less common all the time because of side effects. That’s also true for valproic acid. Many bipolar patients are now prescribed only antidepressants, even though all the guidelines advise against it due to the risk of hypomania. We think that this is a bad trend and that lithium and valproic acid should be prescribed more. Also, as a safety precaution, anyone with bipolar disorder on antidepressants or benzodiazepines or sedatives should be followed especially closely for suicidal signals, because they could carry a really highly increased risk – up to 50% – due to the medication as well.”

He reported having no financial conflicts regarding the study, funded by the Finnish government.

Dr. Lähteenvuo also was first author of a recent study showing that among the various drugs prescribed for treatment of bipolar disorder, lithium was the clear winner for prevention of rehospitalization in the same national Finnish population of more than 18,000 bipolar patients (JAMA Psychiatry. 2018;75[4]:347-55). One expert named this among the top four studies of the year in the field of mood disorders.

[email protected]

BARCELONA – Lithium and valproic acid are the treatments of choice for patients with bipolar disorder at increased risk for suicide, according to the findings of a large Finnish national study.

Bruce Jancin/MDedge News

“We found that – surprise, surprise – lithium and valproic acid had the lowest risk of anyone committing suicide on them. And funnily enough, some antidepressants seemed to be correlated with a higher risk of committing suicide,” Markku Lähteenvuo, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

However, he suspects that the correlation between antidepressant therapy and suicide in bipolar patients probably was caused by confounding by indication.

“I wouldn’t have as a take-home message that SSRI [selective serotonin reuptake inhibitor] antidepressants are bad for you; it’s probably rather that these are really bad cases, treatment gets initiated when someone gets worse, and the antidepressants just aren’t quick enough to really give an effect. It takes 3-4 weeks for an SSRI to really kick in, whereas mood stabilizers like lithium and valproic acid usually kick in almost immediately, within a couple of days to a week,” explained Dr. Lähteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland, in Kuopio.

He presented a study of all suicides among the 18,018 Finnish patients hospitalized for bipolar disorder nationwide during 1996-2012. Using prospective national databases to follow patients for a mean of 7.2 years, he and his coinvestigators were able to determine what medications they were on when they committed suicide and the likelihood they were actually taking their prescribed medications at the time.


In a multivariate proportional hazards analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, intervals of drug exposure and nonexposure, age, sex, and number of hospitalizations for suicidality within the prior 2 years, bipolar patients on lithium had a 67% lower risk of suicide than did those not on the drug. Those on valproic acid were 39% less likely to commit suicide than those not on that mood stabilizer. And bipolar patients on lithium were 42% less likely to die from suicide than those on valproic acid.

At the other extreme, patients on antidepressants were in aggregate 28% more likely to commit suicide than those who were not. This risk varied considerably according to the specific antidepressant: for example, escitalopram and mirtazapine were associated with 71% and 57% greater risks of suicide, respectively, than in patients not on those antidepressants, while patients on paroxetine, venlafaxine, or sertraline were not at increased risk.

Also, the use of sedatives was associated with a 52% greater likelihood of suicide, and benzodiazepines were linked to a 21% increase in risk. Again, as with antidepressants, these associations with increased risk of completed suicide could be attributable in part or in whole to confounding by indication, the psychiatrist noted. He and his colleagues are conducting further analyses examining that possibility.


Pending the outcome of that closer look, however, Dr. Lähteenvuo believes the study’s message to clinicians is clear: “The use of lithium is getting less and less common all the time because of side effects. That’s also true for valproic acid. Many bipolar patients are now prescribed only antidepressants, even though all the guidelines advise against it due to the risk of hypomania. We think that this is a bad trend and that lithium and valproic acid should be prescribed more. Also, as a safety precaution, anyone with bipolar disorder on antidepressants or benzodiazepines or sedatives should be followed especially closely for suicidal signals, because they could carry a really highly increased risk – up to 50% – due to the medication as well.”

He reported having no financial conflicts regarding the study, funded by the Finnish government.

Dr. Lähteenvuo also was first author of a recent study showing that among the various drugs prescribed for treatment of bipolar disorder, lithium was the clear winner for prevention of rehospitalization in the same national Finnish population of more than 18,000 bipolar patients (JAMA Psychiatry. 2018;75[4]:347-55). One expert named this among the top four studies of the year in the field of mood disorders.

[email protected]

Does Thymectomy Benefit Patients With Anti-MuSK Myasthenia Gravis?

Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study.

Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.

To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.

Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).

Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who received thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.

At last visit, 35% (nine of 26) of patients who received thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not receive thymectomy. In addition, 69% of patients who received thymectomy were taking prednisone, compared with 41% of patients who did not receive thymectomy (median dose, 10 mg/day vs 0 mg/day).

“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported.

“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”

The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.

What Are the Clinical, Laboratory, and Electrodiagnostic Features of Zinc Deficiency-InducedPeripheral Neuropathy?

Patients with zinc deficiency-induced peripheral neuropathy may present with paresthesia, gait abnormalities, sensory deficits, reduced tendon reflexes, an abnormal Romberg test, and increased CSF protein, according to a study.

Recognition of the features of zinc deficiency-induced peripheral neuropathy may help neurologists diagnose the disorder and manage patients, researchers said.

“Zinc, an essential trace element, plays a critical role in maintaining normal structural and functional conditions in the body,” said lead author Favio C. Bumanlag, Chief Technologist in the Department of Neurology at the Lewis Katz School of Medicine at Temple University in Philadelphia. “Peripheral nerves are susceptible to damage when zinc deficiency occurs.... Recognition of [zinc deficiency-induced peripheral neuropathy] will help physicians and technologists effectively manage patients.”

To study the clinical and electrophysiologic features of zinc deficiency-induced peripheral neuropathy, Mr. Bumanlag and Jin Luo, MD, PhD, Professor of Neurology and Pharmacology at Temple University, retrospectively reviewed charts in their neuromuscular clinic and EMG laboratory database to identify patients with peripheral neuropathy and zinc deficiency. They included charts from between January 1, 2015, and December 31, 2017, in their review. They excluded patients with abnormal copper levels.

Mr. Bumanlag and Dr. Luo obtained information about patients’ clinical presentations, past medical histories, BMI, neurologic examinations, and laboratory results. They also examined patients’ needle electromyograms and nerve conduction studies.

In all, they identified 12 patients with peripheral neuropathy and zinc deficiency. Patients had a mean age of 55.1. Six were female. Patients’ mean zinc level was 52.5 μg/dL, with a range of 37 μg/dL to 58 μg/dL (reference, 56–134 μg/dL). Mean copper level was 107.6 μg/dL, with a range of 84 μg/dL to 173 μg/dL (reference, 72–166μg/dL). Eleven of the 12 patients had received an electrophysiologic evaluation.

Notable findings in presentation included paresthesia in 75 and gait abnormalities in 42%. One patient was obese (8%), and three patients had diarrhea (25%). Neurologic examination showed sensory deficits in 83%, reduced tendon reflexes in 67%, and an abnormal Romberg test in 67%. Four of five patients had increased CSF protein. Electrophysiologic evaluations showed features of demyelinating peripheral neuropathy (28%) and distally active denervation in the lower extremities.

“Zinc participates in more than 200 enzymatic reactions,” said the researchers. “Unfortunately, zinc deficiency-induced peripheral neuropathy is often misdiagnosed or delayed in diagnosis. Literature on zinc deficiency-induced peripheral neuropathy is sparse.”

Disability in Patients With Stiff Person Syndrome May Progress Faster Than Thought

Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study. In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia.

Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.

The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.

Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.

The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.

“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”

The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.

Does Thymectomy Benefit Patients With Anti-MuSK Myasthenia Gravis?

Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study.

Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.

To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.

Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).

Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who received thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.

At last visit, 35% (nine of 26) of patients who received thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not receive thymectomy. In addition, 69% of patients who received thymectomy were taking prednisone, compared with 41% of patients who did not receive thymectomy (median dose, 10 mg/day vs 0 mg/day).

“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported.

“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”

The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.

What Are the Clinical, Laboratory, and Electrodiagnostic Features of Zinc Deficiency-InducedPeripheral Neuropathy?

Patients with zinc deficiency-induced peripheral neuropathy may present with paresthesia, gait abnormalities, sensory deficits, reduced tendon reflexes, an abnormal Romberg test, and increased CSF protein, according to a study.

Recognition of the features of zinc deficiency-induced peripheral neuropathy may help neurologists diagnose the disorder and manage patients, researchers said.

“Zinc, an essential trace element, plays a critical role in maintaining normal structural and functional conditions in the body,” said lead author Favio C. Bumanlag, Chief Technologist in the Department of Neurology at the Lewis Katz School of Medicine at Temple University in Philadelphia. “Peripheral nerves are susceptible to damage when zinc deficiency occurs.... Recognition of [zinc deficiency-induced peripheral neuropathy] will help physicians and technologists effectively manage patients.”

To study the clinical and electrophysiologic features of zinc deficiency-induced peripheral neuropathy, Mr. Bumanlag and Jin Luo, MD, PhD, Professor of Neurology and Pharmacology at Temple University, retrospectively reviewed charts in their neuromuscular clinic and EMG laboratory database to identify patients with peripheral neuropathy and zinc deficiency. They included charts from between January 1, 2015, and December 31, 2017, in their review. They excluded patients with abnormal copper levels.

Mr. Bumanlag and Dr. Luo obtained information about patients’ clinical presentations, past medical histories, BMI, neurologic examinations, and laboratory results. They also examined patients’ needle electromyograms and nerve conduction studies.

In all, they identified 12 patients with peripheral neuropathy and zinc deficiency. Patients had a mean age of 55.1. Six were female. Patients’ mean zinc level was 52.5 μg/dL, with a range of 37 μg/dL to 58 μg/dL (reference, 56–134 μg/dL). Mean copper level was 107.6 μg/dL, with a range of 84 μg/dL to 173 μg/dL (reference, 72–166μg/dL). Eleven of the 12 patients had received an electrophysiologic evaluation.

Notable findings in presentation included paresthesia in 75 and gait abnormalities in 42%. One patient was obese (8%), and three patients had diarrhea (25%). Neurologic examination showed sensory deficits in 83%, reduced tendon reflexes in 67%, and an abnormal Romberg test in 67%. Four of five patients had increased CSF protein. Electrophysiologic evaluations showed features of demyelinating peripheral neuropathy (28%) and distally active denervation in the lower extremities.

“Zinc participates in more than 200 enzymatic reactions,” said the researchers. “Unfortunately, zinc deficiency-induced peripheral neuropathy is often misdiagnosed or delayed in diagnosis. Literature on zinc deficiency-induced peripheral neuropathy is sparse.”

Disability in Patients With Stiff Person Syndrome May Progress Faster Than Thought

Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study. In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia.

Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.

The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.

Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.

The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.

“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”

The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.

Does Thymectomy Benefit Patients With Anti-MuSK Myasthenia Gravis?

Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study.

Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.

To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.

Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).

Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who received thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.

At last visit, 35% (nine of 26) of patients who received thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not receive thymectomy. In addition, 69% of patients who received thymectomy were taking prednisone, compared with 41% of patients who did not receive thymectomy (median dose, 10 mg/day vs 0 mg/day).

“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported.

“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”

The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.

What Are the Clinical, Laboratory, and Electrodiagnostic Features of Zinc Deficiency-InducedPeripheral Neuropathy?

Patients with zinc deficiency-induced peripheral neuropathy may present with paresthesia, gait abnormalities, sensory deficits, reduced tendon reflexes, an abnormal Romberg test, and increased CSF protein, according to a study.

Recognition of the features of zinc deficiency-induced peripheral neuropathy may help neurologists diagnose the disorder and manage patients, researchers said.

“Zinc, an essential trace element, plays a critical role in maintaining normal structural and functional conditions in the body,” said lead author Favio C. Bumanlag, Chief Technologist in the Department of Neurology at the Lewis Katz School of Medicine at Temple University in Philadelphia. “Peripheral nerves are susceptible to damage when zinc deficiency occurs.... Recognition of [zinc deficiency-induced peripheral neuropathy] will help physicians and technologists effectively manage patients.”

To study the clinical and electrophysiologic features of zinc deficiency-induced peripheral neuropathy, Mr. Bumanlag and Jin Luo, MD, PhD, Professor of Neurology and Pharmacology at Temple University, retrospectively reviewed charts in their neuromuscular clinic and EMG laboratory database to identify patients with peripheral neuropathy and zinc deficiency. They included charts from between January 1, 2015, and December 31, 2017, in their review. They excluded patients with abnormal copper levels.

Mr. Bumanlag and Dr. Luo obtained information about patients’ clinical presentations, past medical histories, BMI, neurologic examinations, and laboratory results. They also examined patients’ needle electromyograms and nerve conduction studies.

In all, they identified 12 patients with peripheral neuropathy and zinc deficiency. Patients had a mean age of 55.1. Six were female. Patients’ mean zinc level was 52.5 μg/dL, with a range of 37 μg/dL to 58 μg/dL (reference, 56–134 μg/dL). Mean copper level was 107.6 μg/dL, with a range of 84 μg/dL to 173 μg/dL (reference, 72–166μg/dL). Eleven of the 12 patients had received an electrophysiologic evaluation.

Notable findings in presentation included paresthesia in 75 and gait abnormalities in 42%. One patient was obese (8%), and three patients had diarrhea (25%). Neurologic examination showed sensory deficits in 83%, reduced tendon reflexes in 67%, and an abnormal Romberg test in 67%. Four of five patients had increased CSF protein. Electrophysiologic evaluations showed features of demyelinating peripheral neuropathy (28%) and distally active denervation in the lower extremities.

“Zinc participates in more than 200 enzymatic reactions,” said the researchers. “Unfortunately, zinc deficiency-induced peripheral neuropathy is often misdiagnosed or delayed in diagnosis. Literature on zinc deficiency-induced peripheral neuropathy is sparse.”

Disability in Patients With Stiff Person Syndrome May Progress Faster Than Thought

Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study. In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia.

Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.

The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.

Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.

The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.

“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”

The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.

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CHICAGO—Use of the CDC case definition for acute flaccid myelitis may lead to misdiagnosis in patients with other conditions, according to research presented at the 47th Annual Meeting of the Child Neurology Society. A review of 45 reported cases of acute flaccid myelitis found that 12 of the patients had other diseases, such as polyradiculoneuropathy, transverse myelitis, spinal cord ischemia, clinically isolated syndrome, meningitis, and myelopathy due to severe Chiari I malformation, said Matthew Elrick, MD, PhD, Clinical Fellow in Neurology at Johns Hopkins Hospital in Baltimore, and colleagues.

Acute flaccid myelitis is a polio-like illness of acute spinal motor neuron injury following viral infection. Recent outbreaks have been reported, but clinical diagnostic criteria are lacking. Clinical characteristics may help differentiate acute flaccid myelitis from other causes of myelopathy, Dr. Elrick said.

Dr. Elrick and colleagues analyzed cases from two patient cohorts. One cohort included patients who were recruited nationwide based on the CDC case definition of acute flaccid myelitis. The other cohort included patients who were referred to the Johns Hopkins Transverse Myelitis Center and received a diagnosis of acute flaccid myelitis. The researchers reviewed patients’ records and imaging data. An independent neurologist reviewed a subset of cases to confirm inter-rater reliability. Characteristics that differed significantly between patients with and without acute flaccid myelitis were used to build a clinical scoring system.

The CDC case definition includes clinical criteria (ie, an illness with onset of acute flaccid limb weakness), confirmatory laboratory evidence (ie, MRI showing spinal cord lesion largely restricted to gray matter and spanning one or more vertebral segments), and supportive laboratory evidence (ie, CSF with pleocytosis). Clinically compatible cases with confirmatory laboratory evidence are considered confirmed, and clinically compatible cases with supportive laboratory evidence are considered probable.

The investigators based their proposed criteria on the physiologic understanding of acute flaccid myelitis as a disease of the motor neuron with features similar to those of poliomyelitis. They refined the criteria based on features commonly seen in apparent cases (eg, weakness involving the limbs, neck, face, or bulbar muscles and prodromal illness with fever, respiratory symptoms, or gastrointestinal symptoms). In addition, they incorporated rule-out criteria to exclude mimics.

Based on the results of their analysis, they developed a clinical scoring system to aid in the bedside diagnosis of acute flaccid myelitis by considering features such as asymmetric onset, decreased tone, and absence of increased tone.

The proposed criteria and clinical scoring system require validation and may be updated in light of data from recent cases of acute flaccid myelitis, Dr. Elrick said.

CHICAGO—Use of the CDC case definition for acute flaccid myelitis may lead to misdiagnosis in patients with other conditions, according to research presented at the 47th Annual Meeting of the Child Neurology Society. A review of 45 reported cases of acute flaccid myelitis found that 12 of the patients had other diseases, such as polyradiculoneuropathy, transverse myelitis, spinal cord ischemia, clinically isolated syndrome, meningitis, and myelopathy due to severe Chiari I malformation, said Matthew Elrick, MD, PhD, Clinical Fellow in Neurology at Johns Hopkins Hospital in Baltimore, and colleagues.

Acute flaccid myelitis is a polio-like illness of acute spinal motor neuron injury following viral infection. Recent outbreaks have been reported, but clinical diagnostic criteria are lacking. Clinical characteristics may help differentiate acute flaccid myelitis from other causes of myelopathy, Dr. Elrick said.

Dr. Elrick and colleagues analyzed cases from two patient cohorts. One cohort included patients who were recruited nationwide based on the CDC case definition of acute flaccid myelitis. The other cohort included patients who were referred to the Johns Hopkins Transverse Myelitis Center and received a diagnosis of acute flaccid myelitis. The researchers reviewed patients’ records and imaging data. An independent neurologist reviewed a subset of cases to confirm inter-rater reliability. Characteristics that differed significantly between patients with and without acute flaccid myelitis were used to build a clinical scoring system.

The CDC case definition includes clinical criteria (ie, an illness with onset of acute flaccid limb weakness), confirmatory laboratory evidence (ie, MRI showing spinal cord lesion largely restricted to gray matter and spanning one or more vertebral segments), and supportive laboratory evidence (ie, CSF with pleocytosis). Clinically compatible cases with confirmatory laboratory evidence are considered confirmed, and clinically compatible cases with supportive laboratory evidence are considered probable.

The investigators based their proposed criteria on the physiologic understanding of acute flaccid myelitis as a disease of the motor neuron with features similar to those of poliomyelitis. They refined the criteria based on features commonly seen in apparent cases (eg, weakness involving the limbs, neck, face, or bulbar muscles and prodromal illness with fever, respiratory symptoms, or gastrointestinal symptoms). In addition, they incorporated rule-out criteria to exclude mimics.

Based on the results of their analysis, they developed a clinical scoring system to aid in the bedside diagnosis of acute flaccid myelitis by considering features such as asymmetric onset, decreased tone, and absence of increased tone.

The proposed criteria and clinical scoring system require validation and may be updated in light of data from recent cases of acute flaccid myelitis, Dr. Elrick said.

CHICAGO—Use of the CDC case definition for acute flaccid myelitis may lead to misdiagnosis in patients with other conditions, according to research presented at the 47th Annual Meeting of the Child Neurology Society. A review of 45 reported cases of acute flaccid myelitis found that 12 of the patients had other diseases, such as polyradiculoneuropathy, transverse myelitis, spinal cord ischemia, clinically isolated syndrome, meningitis, and myelopathy due to severe Chiari I malformation, said Matthew Elrick, MD, PhD, Clinical Fellow in Neurology at Johns Hopkins Hospital in Baltimore, and colleagues.

Acute flaccid myelitis is a polio-like illness of acute spinal motor neuron injury following viral infection. Recent outbreaks have been reported, but clinical diagnostic criteria are lacking. Clinical characteristics may help differentiate acute flaccid myelitis from other causes of myelopathy, Dr. Elrick said.

Dr. Elrick and colleagues analyzed cases from two patient cohorts. One cohort included patients who were recruited nationwide based on the CDC case definition of acute flaccid myelitis. The other cohort included patients who were referred to the Johns Hopkins Transverse Myelitis Center and received a diagnosis of acute flaccid myelitis. The researchers reviewed patients’ records and imaging data. An independent neurologist reviewed a subset of cases to confirm inter-rater reliability. Characteristics that differed significantly between patients with and without acute flaccid myelitis were used to build a clinical scoring system.

The CDC case definition includes clinical criteria (ie, an illness with onset of acute flaccid limb weakness), confirmatory laboratory evidence (ie, MRI showing spinal cord lesion largely restricted to gray matter and spanning one or more vertebral segments), and supportive laboratory evidence (ie, CSF with pleocytosis). Clinically compatible cases with confirmatory laboratory evidence are considered confirmed, and clinically compatible cases with supportive laboratory evidence are considered probable.

The investigators based their proposed criteria on the physiologic understanding of acute flaccid myelitis as a disease of the motor neuron with features similar to those of poliomyelitis. They refined the criteria based on features commonly seen in apparent cases (eg, weakness involving the limbs, neck, face, or bulbar muscles and prodromal illness with fever, respiratory symptoms, or gastrointestinal symptoms). In addition, they incorporated rule-out criteria to exclude mimics.

Based on the results of their analysis, they developed a clinical scoring system to aid in the bedside diagnosis of acute flaccid myelitis by considering features such as asymmetric onset, decreased tone, and absence of increased tone.

The proposed criteria and clinical scoring system require validation and may be updated in light of data from recent cases of acute flaccid myelitis, Dr. Elrick said.

BERLIN—Higher vitamin D levels at multiple sclerosis (MS) onset predict higher cognitive function 11 years later, according to research presented at ECTRIMS 2018. People who are heavy smokers at MS onset have a clinically significant decline in cognitive function at 11 years, according to the researchers.

“Higher vitamin D in the first years after clinically isolated syndrome (CIS) was associated with better cognitive function and lower neuronal injury at Year 11,” said Marianna Cortese, MD, a research fellow at the Harvard T.H. Chan School of Public Health in Boston. “Vitamin D supplementation during the early years with the disease might be neuroprotective.”

The BENEFIT-11 Trial

According to Dr. Cortese, 40% to 70% of patients with MS experience cognitive decline during their disease course. There is no specific treatment for cognitive decline.

Smoking, low levels of vitamin D, and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS and have been associated with more active MS and progressive disease. Whether these factors predict cognitive status had not been known, said Dr. Cortese.

Investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The observational study followed 278 participants with CIS in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled study of interferon beta-1b for the early treatment of CIS. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first two years after CIS to predict progression outcomes at Year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline and at study Months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used to indicate EBV seropositivity.

The cognitive performance measure used in the study was the Paced Auditory Serial Addition Test (PASAT), a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study Years 1, 2, 5, and 11. At study Year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the researchers adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease on baseline MRI, BMI, and whether the patient was treated with steroids during CIS.

Vitamin D Protected Against Neuroaxonal Injury

“Higher quintiles of mean vitamin D levels during the first two years were associated with lower odds of scoring worse on the PASAT at Year 11,” said Dr. Cortese. The significant trend across the quintiles suggests a dose–response relationship, she said. Dr. Cortese explained that “scoring worse” meant scoring below the median.

A 50-nmol/L increase in mean 25(OH)D in study Months 6 through 24 predicted 65% lower odds of having a PASAT score below the median at Year 11. “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Cotinine levels obtained during the first two years were used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker. If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the nine patients who were heavy smokers, as indicated by cotinine levels over 189 ng/mL.

“Smokers, compared to nonsmokers, had a significantly lower standardized PASAT score at Year 11,” said Dr. Cortese. “Heavy smokers had an up to 0.6-standard deviation-lower PASAT score at Year 11.... This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.” Early smoking had a dose–response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients,” said Dr. Cortese.

Epstein-Barr antibodies were not associated with cognitive function at Year 11.

“The findings of neuroaxonal injury at Year 11 using serum neurofilament light chain measures corroborated the main findings on cognitive function at Year 11,” said Dr. Cortese. A 50-nmol increase in vitamin D level within the first five years was associated with 20% lower neurofilament light chain levels at Year 11, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first five years had neurofilament light chain levels that were 20% higher than those of other participants. “They had more neuroaxonal loss,” said Dr. Cortese. Neurofilament light chain levels at Year 11 were not associated with early EBV status, she said.

Radiologic and other clinical data from BENEFIT-11 are also being studied and will be reported in the future, said Dr. Cortese.

Dr. Cortese reported no conflicts of interest. Several coauthors reported financial relationships with pharmaceutical companies. The study was supported by the NIH and the National MS Society, with clinical support from Bayer HealthCare.

—Kari Oakes

BERLIN—Higher vitamin D levels at multiple sclerosis (MS) onset predict higher cognitive function 11 years later, according to research presented at ECTRIMS 2018. People who are heavy smokers at MS onset have a clinically significant decline in cognitive function at 11 years, according to the researchers.

“Higher vitamin D in the first years after clinically isolated syndrome (CIS) was associated with better cognitive function and lower neuronal injury at Year 11,” said Marianna Cortese, MD, a research fellow at the Harvard T.H. Chan School of Public Health in Boston. “Vitamin D supplementation during the early years with the disease might be neuroprotective.”

The BENEFIT-11 Trial

According to Dr. Cortese, 40% to 70% of patients with MS experience cognitive decline during their disease course. There is no specific treatment for cognitive decline.

Smoking, low levels of vitamin D, and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS and have been associated with more active MS and progressive disease. Whether these factors predict cognitive status had not been known, said Dr. Cortese.

Investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The observational study followed 278 participants with CIS in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled study of interferon beta-1b for the early treatment of CIS. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first two years after CIS to predict progression outcomes at Year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline and at study Months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used to indicate EBV seropositivity.

The cognitive performance measure used in the study was the Paced Auditory Serial Addition Test (PASAT), a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study Years 1, 2, 5, and 11. At study Year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the researchers adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease on baseline MRI, BMI, and whether the patient was treated with steroids during CIS.

Vitamin D Protected Against Neuroaxonal Injury

“Higher quintiles of mean vitamin D levels during the first two years were associated with lower odds of scoring worse on the PASAT at Year 11,” said Dr. Cortese. The significant trend across the quintiles suggests a dose–response relationship, she said. Dr. Cortese explained that “scoring worse” meant scoring below the median.

A 50-nmol/L increase in mean 25(OH)D in study Months 6 through 24 predicted 65% lower odds of having a PASAT score below the median at Year 11. “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Cotinine levels obtained during the first two years were used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker. If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the nine patients who were heavy smokers, as indicated by cotinine levels over 189 ng/mL.

“Smokers, compared to nonsmokers, had a significantly lower standardized PASAT score at Year 11,” said Dr. Cortese. “Heavy smokers had an up to 0.6-standard deviation-lower PASAT score at Year 11.... This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.” Early smoking had a dose–response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients,” said Dr. Cortese.

Epstein-Barr antibodies were not associated with cognitive function at Year 11.

“The findings of neuroaxonal injury at Year 11 using serum neurofilament light chain measures corroborated the main findings on cognitive function at Year 11,” said Dr. Cortese. A 50-nmol increase in vitamin D level within the first five years was associated with 20% lower neurofilament light chain levels at Year 11, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first five years had neurofilament light chain levels that were 20% higher than those of other participants. “They had more neuroaxonal loss,” said Dr. Cortese. Neurofilament light chain levels at Year 11 were not associated with early EBV status, she said.

Radiologic and other clinical data from BENEFIT-11 are also being studied and will be reported in the future, said Dr. Cortese.

Dr. Cortese reported no conflicts of interest. Several coauthors reported financial relationships with pharmaceutical companies. The study was supported by the NIH and the National MS Society, with clinical support from Bayer HealthCare.

—Kari Oakes

BERLIN—Higher vitamin D levels at multiple sclerosis (MS) onset predict higher cognitive function 11 years later, according to research presented at ECTRIMS 2018. People who are heavy smokers at MS onset have a clinically significant decline in cognitive function at 11 years, according to the researchers.

“Higher vitamin D in the first years after clinically isolated syndrome (CIS) was associated with better cognitive function and lower neuronal injury at Year 11,” said Marianna Cortese, MD, a research fellow at the Harvard T.H. Chan School of Public Health in Boston. “Vitamin D supplementation during the early years with the disease might be neuroprotective.”

The BENEFIT-11 Trial

According to Dr. Cortese, 40% to 70% of patients with MS experience cognitive decline during their disease course. There is no specific treatment for cognitive decline.

Smoking, low levels of vitamin D, and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS and have been associated with more active MS and progressive disease. Whether these factors predict cognitive status had not been known, said Dr. Cortese.

Investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The observational study followed 278 participants with CIS in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled study of interferon beta-1b for the early treatment of CIS. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first two years after CIS to predict progression outcomes at Year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline and at study Months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used to indicate EBV seropositivity.

The cognitive performance measure used in the study was the Paced Auditory Serial Addition Test (PASAT), a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study Years 1, 2, 5, and 11. At study Year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the researchers adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease on baseline MRI, BMI, and whether the patient was treated with steroids during CIS.

Vitamin D Protected Against Neuroaxonal Injury

“Higher quintiles of mean vitamin D levels during the first two years were associated with lower odds of scoring worse on the PASAT at Year 11,” said Dr. Cortese. The significant trend across the quintiles suggests a dose–response relationship, she said. Dr. Cortese explained that “scoring worse” meant scoring below the median.

A 50-nmol/L increase in mean 25(OH)D in study Months 6 through 24 predicted 65% lower odds of having a PASAT score below the median at Year 11. “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Cotinine levels obtained during the first two years were used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker. If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the nine patients who were heavy smokers, as indicated by cotinine levels over 189 ng/mL.

“Smokers, compared to nonsmokers, had a significantly lower standardized PASAT score at Year 11,” said Dr. Cortese. “Heavy smokers had an up to 0.6-standard deviation-lower PASAT score at Year 11.... This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.” Early smoking had a dose–response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients,” said Dr. Cortese.

Epstein-Barr antibodies were not associated with cognitive function at Year 11.

“The findings of neuroaxonal injury at Year 11 using serum neurofilament light chain measures corroborated the main findings on cognitive function at Year 11,” said Dr. Cortese. A 50-nmol increase in vitamin D level within the first five years was associated with 20% lower neurofilament light chain levels at Year 11, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first five years had neurofilament light chain levels that were 20% higher than those of other participants. “They had more neuroaxonal loss,” said Dr. Cortese. Neurofilament light chain levels at Year 11 were not associated with early EBV status, she said.

Radiologic and other clinical data from BENEFIT-11 are also being studied and will be reported in the future, said Dr. Cortese.

Dr. Cortese reported no conflicts of interest. Several coauthors reported financial relationships with pharmaceutical companies. The study was supported by the NIH and the National MS Society, with clinical support from Bayer HealthCare.

—Kari Oakes

ATLANTA—Chronic gastroesophageal reflux disease (GERD) is associated with various sleep disorders that might complicate the response to GERD treatment, according to an ongoing longitudinal analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“We have little longitudinal information on GERD in the general population; the last published article on GERD incidence was 20 years ago,” said lead study author Maurice M. Ohayon, MD, DSc, PhD, Director of the Stanford Sleep Epidemiology Research Center in California. “As a sleep specialist, I am always interested to see how a specific medical condition may affect the sleep quality of the individuals with that condition. How we live our day has an impact on our night; it works together.”

Proton-Pump Inhibitors Are Common Treatments

To examine the long-term effects of GERD on sleep disturbances, Dr. Ohayon and his colleagues used US Census data to identify a random sample of adults in Arizona, California, Colorado, Idaho, New York, Oregon, Pennsylvania, and Texas. The researchers conducted two waves of phone interviews with the subjects three years apart, beginning in 2004. They limited their analysis to 10,930 subjects with a mean age of 43 who participated in both interviews.

Between Wave 1 and Wave 2 of phone interviews, the proportion of adults who reported having GERD rose from 10.6% to 12.4%. The prevalence of new GERD cases was 8.5% per year, while the incidence was 3.2% per year. Chronic GERD, defined as GERD present during both interview periods, was observed in 3.9% of the sample.

The researchers found that 77.3% of subjects with GERD were taking a treatment, mostly proton-pump inhibitors, to alleviate their symptoms. Those with chronic GERD were more likely to report being dissatisfied with their sleep during Wave 2 of the study, compared with Wave 1 (24.2% vs 13.5%). In addition, compared with their counterparts without GERD, those with chronic GERD were more likely to wake up at night (33.9% vs 28.3%) and to have nonrestorative sleep (15.6% vs 10.5%).

“Discomfort related to GERD may happen while you are sleeping,” said Dr. Ohayon. “It may wake you up and, if not, it may make you feel unrested when you wake up. We observed both of these symptoms in our GERD participants. Insomnia disorders were also rampant in the chronic GERD group (24.5%, compared with 14.4% in non-GERD participants). An insomnia disorder is more than just having difficulty falling asleep or waking up at night, it means that your daytime functioning is affected by the poor quality of your night.”

GERD May Promote Weight Gain

Other findings from the study were “rather alarming,” said Dr. Ohayon. For example, individuals with GERD, especially those with the chronic form, weighed much more than those with no GERD did. “Over a three-year period, the chronic GERD individuals gained one point in the BMI, which for a six-foot tall man translates into a weight gain of 30 pounds,” he said. “Of course, with that follows high blood pressure, high cholesterol, diabetes, chronic pain, and heart disease.”

He concluded that GERD has its main manifestations when affected individuals are sleeping on their backs. “The impact of GERD on the quality of sleep is major,” he said. “Sleepiness and fatigue during the day are the consequences impacting work, family, and quality of life.”

Dr. Ohayon acknowledged certain limitations of the study, including the fact that the diagnosis of GERD was based on self-report. The study was supported by an unrestricted grant from Takeda.

—Doug Brunk

ATLANTA—Chronic gastroesophageal reflux disease (GERD) is associated with various sleep disorders that might complicate the response to GERD treatment, according to an ongoing longitudinal analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“We have little longitudinal information on GERD in the general population; the last published article on GERD incidence was 20 years ago,” said lead study author Maurice M. Ohayon, MD, DSc, PhD, Director of the Stanford Sleep Epidemiology Research Center in California. “As a sleep specialist, I am always interested to see how a specific medical condition may affect the sleep quality of the individuals with that condition. How we live our day has an impact on our night; it works together.”

Proton-Pump Inhibitors Are Common Treatments

To examine the long-term effects of GERD on sleep disturbances, Dr. Ohayon and his colleagues used US Census data to identify a random sample of adults in Arizona, California, Colorado, Idaho, New York, Oregon, Pennsylvania, and Texas. The researchers conducted two waves of phone interviews with the subjects three years apart, beginning in 2004. They limited their analysis to 10,930 subjects with a mean age of 43 who participated in both interviews.

Between Wave 1 and Wave 2 of phone interviews, the proportion of adults who reported having GERD rose from 10.6% to 12.4%. The prevalence of new GERD cases was 8.5% per year, while the incidence was 3.2% per year. Chronic GERD, defined as GERD present during both interview periods, was observed in 3.9% of the sample.

The researchers found that 77.3% of subjects with GERD were taking a treatment, mostly proton-pump inhibitors, to alleviate their symptoms. Those with chronic GERD were more likely to report being dissatisfied with their sleep during Wave 2 of the study, compared with Wave 1 (24.2% vs 13.5%). In addition, compared with their counterparts without GERD, those with chronic GERD were more likely to wake up at night (33.9% vs 28.3%) and to have nonrestorative sleep (15.6% vs 10.5%).

“Discomfort related to GERD may happen while you are sleeping,” said Dr. Ohayon. “It may wake you up and, if not, it may make you feel unrested when you wake up. We observed both of these symptoms in our GERD participants. Insomnia disorders were also rampant in the chronic GERD group (24.5%, compared with 14.4% in non-GERD participants). An insomnia disorder is more than just having difficulty falling asleep or waking up at night, it means that your daytime functioning is affected by the poor quality of your night.”

GERD May Promote Weight Gain

Other findings from the study were “rather alarming,” said Dr. Ohayon. For example, individuals with GERD, especially those with the chronic form, weighed much more than those with no GERD did. “Over a three-year period, the chronic GERD individuals gained one point in the BMI, which for a six-foot tall man translates into a weight gain of 30 pounds,” he said. “Of course, with that follows high blood pressure, high cholesterol, diabetes, chronic pain, and heart disease.”

He concluded that GERD has its main manifestations when affected individuals are sleeping on their backs. “The impact of GERD on the quality of sleep is major,” he said. “Sleepiness and fatigue during the day are the consequences impacting work, family, and quality of life.”

Dr. Ohayon acknowledged certain limitations of the study, including the fact that the diagnosis of GERD was based on self-report. The study was supported by an unrestricted grant from Takeda.

—Doug Brunk

ATLANTA—Chronic gastroesophageal reflux disease (GERD) is associated with various sleep disorders that might complicate the response to GERD treatment, according to an ongoing longitudinal analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“We have little longitudinal information on GERD in the general population; the last published article on GERD incidence was 20 years ago,” said lead study author Maurice M. Ohayon, MD, DSc, PhD, Director of the Stanford Sleep Epidemiology Research Center in California. “As a sleep specialist, I am always interested to see how a specific medical condition may affect the sleep quality of the individuals with that condition. How we live our day has an impact on our night; it works together.”

Proton-Pump Inhibitors Are Common Treatments

To examine the long-term effects of GERD on sleep disturbances, Dr. Ohayon and his colleagues used US Census data to identify a random sample of adults in Arizona, California, Colorado, Idaho, New York, Oregon, Pennsylvania, and Texas. The researchers conducted two waves of phone interviews with the subjects three years apart, beginning in 2004. They limited their analysis to 10,930 subjects with a mean age of 43 who participated in both interviews.

Between Wave 1 and Wave 2 of phone interviews, the proportion of adults who reported having GERD rose from 10.6% to 12.4%. The prevalence of new GERD cases was 8.5% per year, while the incidence was 3.2% per year. Chronic GERD, defined as GERD present during both interview periods, was observed in 3.9% of the sample.

The researchers found that 77.3% of subjects with GERD were taking a treatment, mostly proton-pump inhibitors, to alleviate their symptoms. Those with chronic GERD were more likely to report being dissatisfied with their sleep during Wave 2 of the study, compared with Wave 1 (24.2% vs 13.5%). In addition, compared with their counterparts without GERD, those with chronic GERD were more likely to wake up at night (33.9% vs 28.3%) and to have nonrestorative sleep (15.6% vs 10.5%).

“Discomfort related to GERD may happen while you are sleeping,” said Dr. Ohayon. “It may wake you up and, if not, it may make you feel unrested when you wake up. We observed both of these symptoms in our GERD participants. Insomnia disorders were also rampant in the chronic GERD group (24.5%, compared with 14.4% in non-GERD participants). An insomnia disorder is more than just having difficulty falling asleep or waking up at night, it means that your daytime functioning is affected by the poor quality of your night.”

GERD May Promote Weight Gain

Other findings from the study were “rather alarming,” said Dr. Ohayon. For example, individuals with GERD, especially those with the chronic form, weighed much more than those with no GERD did. “Over a three-year period, the chronic GERD individuals gained one point in the BMI, which for a six-foot tall man translates into a weight gain of 30 pounds,” he said. “Of course, with that follows high blood pressure, high cholesterol, diabetes, chronic pain, and heart disease.”

He concluded that GERD has its main manifestations when affected individuals are sleeping on their backs. “The impact of GERD on the quality of sleep is major,” he said. “Sleepiness and fatigue during the day are the consequences impacting work, family, and quality of life.”

Dr. Ohayon acknowledged certain limitations of the study, including the fact that the diagnosis of GERD was based on self-report. The study was supported by an unrestricted grant from Takeda.

—Doug Brunk