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Caffeinated coffee intake linked to lower rosacea risk
Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.
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.
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.
This study shows an inverse association between caffeine intake and incidence rosacea, which suggests that patients with rosacea need not avoid coffee, according to Mackenzie R. Wehner, MD, and Eleni Linos, MD, MPH.
For everyone else, the findings offer yet another reason to keep indulging in one of “life’s habitual pleasures,” they wrote. “We will raise an insulated travel mug to that.”
This latest study fits in with numerous studies suggesting coffee may be protective against a number of maladies, including cancer, cardiovascular disease, type 2 diabetes, and Parkinson’s disease, they wrote in their editorial published in JAMA Dermatology.
However, this is an observational study, not a rigorous, randomized trial that could more conclusively prove coffee actually provides an antirosacea benefit that cannot be explained by other factors, such as systematic differences between people who do and do not drink coffee. Enrollment of all women, mostly white, in the Nurses’ Health Study II is another limitation, they added.
Nevertheless, studies like this are the “next-best option” in lieu of randomized, controlled trials to evaluate these relationships, they wrote. “Importantly, the strength of the protective effect noted and the dose-response relationship with increasing coffee and caffeine intake are convincing.”
Dr. Wehner , is with the department of dermatology at the University of Pennsylvania, Philadelphia. Dr. Linos is with the department of dermatology at the University of California, San Francisco. Dr. Wehner reported support from a National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health Dermatology Research Training grant. Dr. Linos reported support from the National Cancer Institute and the National Institute of Aging.
This study shows an inverse association between caffeine intake and incidence rosacea, which suggests that patients with rosacea need not avoid coffee, according to Mackenzie R. Wehner, MD, and Eleni Linos, MD, MPH.
For everyone else, the findings offer yet another reason to keep indulging in one of “life’s habitual pleasures,” they wrote. “We will raise an insulated travel mug to that.”
This latest study fits in with numerous studies suggesting coffee may be protective against a number of maladies, including cancer, cardiovascular disease, type 2 diabetes, and Parkinson’s disease, they wrote in their editorial published in JAMA Dermatology.
However, this is an observational study, not a rigorous, randomized trial that could more conclusively prove coffee actually provides an antirosacea benefit that cannot be explained by other factors, such as systematic differences between people who do and do not drink coffee. Enrollment of all women, mostly white, in the Nurses’ Health Study II is another limitation, they added.
Nevertheless, studies like this are the “next-best option” in lieu of randomized, controlled trials to evaluate these relationships, they wrote. “Importantly, the strength of the protective effect noted and the dose-response relationship with increasing coffee and caffeine intake are convincing.”
Dr. Wehner , is with the department of dermatology at the University of Pennsylvania, Philadelphia. Dr. Linos is with the department of dermatology at the University of California, San Francisco. Dr. Wehner reported support from a National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health Dermatology Research Training grant. Dr. Linos reported support from the National Cancer Institute and the National Institute of Aging.
This study shows an inverse association between caffeine intake and incidence rosacea, which suggests that patients with rosacea need not avoid coffee, according to Mackenzie R. Wehner, MD, and Eleni Linos, MD, MPH.
For everyone else, the findings offer yet another reason to keep indulging in one of “life’s habitual pleasures,” they wrote. “We will raise an insulated travel mug to that.”
This latest study fits in with numerous studies suggesting coffee may be protective against a number of maladies, including cancer, cardiovascular disease, type 2 diabetes, and Parkinson’s disease, they wrote in their editorial published in JAMA Dermatology.
However, this is an observational study, not a rigorous, randomized trial that could more conclusively prove coffee actually provides an antirosacea benefit that cannot be explained by other factors, such as systematic differences between people who do and do not drink coffee. Enrollment of all women, mostly white, in the Nurses’ Health Study II is another limitation, they added.
Nevertheless, studies like this are the “next-best option” in lieu of randomized, controlled trials to evaluate these relationships, they wrote. “Importantly, the strength of the protective effect noted and the dose-response relationship with increasing coffee and caffeine intake are convincing.”
Dr. Wehner , is with the department of dermatology at the University of Pennsylvania, Philadelphia. Dr. Linos is with the department of dermatology at the University of California, San Francisco. Dr. Wehner reported support from a National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health Dermatology Research Training grant. Dr. Linos reported support from the National Cancer Institute and the National Institute of Aging.
Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.
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.
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.
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.
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.
FROM JAMA DERMATOLOGY
Key clinical point: Caffeinated coffee intake was linked to decreased incidence of rosacea, while decaffeinated coffee and noncoffee sources of caffeine had no such effect.
Major finding: Consuming four or more servings of caffeinated coffee was associated with lower risk of rosacea versus one or fewer servings per month (hazard ratio, 0.77; P less than .001).
Study details: An analysis based on 82,737 participants in the Nurses’ Health Study II who responded to a question about rosacea.
Disclosures: Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from National Institutes of Health grants for the Nurses’ Health Study II and other sources.
Source: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.
Dulaglutide meets primary endpoint in REWIND
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.
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.
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.
Mood stabilizers protect bipolar patients from suicide
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.
“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.
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.
“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.
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.
“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.
REPORTING FROM THE ECNP CONGRESS
Key clinical point: Lithium and valproic acid protect patients with bipolar disorder from suicide.
Major finding: The likelihood of suicide was reduced by two-thirds in bipolar patients on lithium, compared with that of patients not on the mood stabilizer.
Study details: This was a retrospective study of more than 18,000 Finnish patients hospitalized at some point for bipolar disorder and the medications they were on when a subset of them committed suicide.
Disclosures: The presenter reported having no financial conflicts regarding the study, funded by the Finnish government.
Conference News Roundup—American Association of Neuromuscular & Electrodiagnostic Medicine
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, 72–166
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, 72–166
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, 72–166
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.
Inpatient Dermatology: Developing Standards of Care for Hospitalized Patients With Skin Disease
Clinical Scoring System May Help Diagnose Acute Flaccid Myelitis
Proposed diagnostic criteria require validation.
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
Proposed diagnostic criteria require validation.
Proposed diagnostic criteria require validation.
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
Vitamin D Levels at Onset Predict Subsequent Cognition in MS
Smoking at baseline is associated with an increased risk of cognitive decline at Year 11.
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.
“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
Smoking at baseline is associated with an increased risk of cognitive decline at Year 11.
Smoking at baseline is associated with an increased risk of cognitive decline at Year 11.
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.
“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.
“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
Study Explores Link Between GERD and Poor Sleep Quality
The proportion of adults with GERD has increased, and GERD increases the likelihood of dissatisfaction with sleep.
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
The proportion of adults with GERD has increased, and GERD increases the likelihood of dissatisfaction with sleep.
The proportion of adults with GERD has increased, and GERD increases the likelihood of dissatisfaction with sleep.
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
To Escalate or Not to Escalate MS Therapy After Relapses?
Switching from a moderately effective treatment to a highly effective treatment can improve outcomes.
BERLIN—Relapse-induced escalation to a highly effective disease-modifying therapy (DMT) is associated with a reduced risk of relapses, according to comprehensive nationwide data from Danish patients with multiple sclerosis (MS). Escalation is associated with a statistically nonsignificant trend toward reduced time to first one-point worsening of Expanded Disability Status Scale (EDSS) score over the short-to-medium term. “Escalation of therapy to a highly effective DMT when patients experience relapses on a moderately effective DMT is recommended to improve control of relapse activity,” said Thor Ameri Chalmer, MD, a doctoral student at Rigshospitalet in Copenhagen, and colleagues at ECTRIMS 2018.
Patients with relapsing-remitting MS who have relapses often switch to a new DMT. Treatment guidelines recommend switching to a highly effective DMT when a patient experiences clinical disease breakthrough. Nevertheless, patients may switch between moderately effective DMTs because of breakthrough disease or adverse effects. Dr. Chalmer and colleagues compared treatment effectiveness between highly effective DMTs and moderately effective DMTs in patients with relapsing-remitting MS who switch therapy because of relapse activity.
In this registry-based cohort study, the investigators retrieved data from the Danish MS Registry on all adults with relapsing-remitting MS. Eligible participants had an EDSS score below 6, experienced a relapse while treated with a moderately effective DMT, and consequently switched to a highly effective DMT or another moderately effective DMT. The groups were compared from treatment initiation until outcome or censoring. Censoring was defined as postbaseline switch between highly effective DMT and moderately effective DMT, cessation of therapy, relocation, or death, whichever occurred first. The primary outcomes were annualized relapse rate (ARR), relapse rate ratio, time to first relapse, and time to first one-point confirmed EDSS worsening. Dr. Chalmer and colleagues used propensity score matching to balance groups, a Cox proportional hazards model to obtain hazard ratios (HR) when modeling time to first relapse and time to first worsening, and negative binomial regression to obtain ARR and relapse rate ratios.
The matched cohort included 814 patients (407 in each group). The median follow-up time was 3.2 years. The group of patients who switched to a highly effective DMT had a 39% lower hazard rate of reaching first relapse (HR, 0.61). ARRs were 0.21 for patients who switched to a highly effective DMT and 0.34 for patients who switched to a moderately effective DMT. Relapse rate ratio for highly effective DMT compared with moderately effective DMT was 0.62. The group who switched to a highly effective DMT had 13% lower hazard rate of one-point EDSS worsening (HR, 0.87).
Switching from a moderately effective treatment to a highly effective treatment can improve outcomes.
Switching from a moderately effective treatment to a highly effective treatment can improve outcomes.
BERLIN—Relapse-induced escalation to a highly effective disease-modifying therapy (DMT) is associated with a reduced risk of relapses, according to comprehensive nationwide data from Danish patients with multiple sclerosis (MS). Escalation is associated with a statistically nonsignificant trend toward reduced time to first one-point worsening of Expanded Disability Status Scale (EDSS) score over the short-to-medium term. “Escalation of therapy to a highly effective DMT when patients experience relapses on a moderately effective DMT is recommended to improve control of relapse activity,” said Thor Ameri Chalmer, MD, a doctoral student at Rigshospitalet in Copenhagen, and colleagues at ECTRIMS 2018.
Patients with relapsing-remitting MS who have relapses often switch to a new DMT. Treatment guidelines recommend switching to a highly effective DMT when a patient experiences clinical disease breakthrough. Nevertheless, patients may switch between moderately effective DMTs because of breakthrough disease or adverse effects. Dr. Chalmer and colleagues compared treatment effectiveness between highly effective DMTs and moderately effective DMTs in patients with relapsing-remitting MS who switch therapy because of relapse activity.
In this registry-based cohort study, the investigators retrieved data from the Danish MS Registry on all adults with relapsing-remitting MS. Eligible participants had an EDSS score below 6, experienced a relapse while treated with a moderately effective DMT, and consequently switched to a highly effective DMT or another moderately effective DMT. The groups were compared from treatment initiation until outcome or censoring. Censoring was defined as postbaseline switch between highly effective DMT and moderately effective DMT, cessation of therapy, relocation, or death, whichever occurred first. The primary outcomes were annualized relapse rate (ARR), relapse rate ratio, time to first relapse, and time to first one-point confirmed EDSS worsening. Dr. Chalmer and colleagues used propensity score matching to balance groups, a Cox proportional hazards model to obtain hazard ratios (HR) when modeling time to first relapse and time to first worsening, and negative binomial regression to obtain ARR and relapse rate ratios.
The matched cohort included 814 patients (407 in each group). The median follow-up time was 3.2 years. The group of patients who switched to a highly effective DMT had a 39% lower hazard rate of reaching first relapse (HR, 0.61). ARRs were 0.21 for patients who switched to a highly effective DMT and 0.34 for patients who switched to a moderately effective DMT. Relapse rate ratio for highly effective DMT compared with moderately effective DMT was 0.62. The group who switched to a highly effective DMT had 13% lower hazard rate of one-point EDSS worsening (HR, 0.87).
BERLIN—Relapse-induced escalation to a highly effective disease-modifying therapy (DMT) is associated with a reduced risk of relapses, according to comprehensive nationwide data from Danish patients with multiple sclerosis (MS). Escalation is associated with a statistically nonsignificant trend toward reduced time to first one-point worsening of Expanded Disability Status Scale (EDSS) score over the short-to-medium term. “Escalation of therapy to a highly effective DMT when patients experience relapses on a moderately effective DMT is recommended to improve control of relapse activity,” said Thor Ameri Chalmer, MD, a doctoral student at Rigshospitalet in Copenhagen, and colleagues at ECTRIMS 2018.
Patients with relapsing-remitting MS who have relapses often switch to a new DMT. Treatment guidelines recommend switching to a highly effective DMT when a patient experiences clinical disease breakthrough. Nevertheless, patients may switch between moderately effective DMTs because of breakthrough disease or adverse effects. Dr. Chalmer and colleagues compared treatment effectiveness between highly effective DMTs and moderately effective DMTs in patients with relapsing-remitting MS who switch therapy because of relapse activity.
In this registry-based cohort study, the investigators retrieved data from the Danish MS Registry on all adults with relapsing-remitting MS. Eligible participants had an EDSS score below 6, experienced a relapse while treated with a moderately effective DMT, and consequently switched to a highly effective DMT or another moderately effective DMT. The groups were compared from treatment initiation until outcome or censoring. Censoring was defined as postbaseline switch between highly effective DMT and moderately effective DMT, cessation of therapy, relocation, or death, whichever occurred first. The primary outcomes were annualized relapse rate (ARR), relapse rate ratio, time to first relapse, and time to first one-point confirmed EDSS worsening. Dr. Chalmer and colleagues used propensity score matching to balance groups, a Cox proportional hazards model to obtain hazard ratios (HR) when modeling time to first relapse and time to first worsening, and negative binomial regression to obtain ARR and relapse rate ratios.
The matched cohort included 814 patients (407 in each group). The median follow-up time was 3.2 years. The group of patients who switched to a highly effective DMT had a 39% lower hazard rate of reaching first relapse (HR, 0.61). ARRs were 0.21 for patients who switched to a highly effective DMT and 0.34 for patients who switched to a moderately effective DMT. Relapse rate ratio for highly effective DMT compared with moderately effective DMT was 0.62. The group who switched to a highly effective DMT had 13% lower hazard rate of one-point EDSS worsening (HR, 0.87).
Migraine Elevates the Risk of Perioperative Stroke
Migraineurs are more likely to have an ischemic stroke in the 30 days after surgery, compared with patients without a history of migraine.
ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scienti
“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.
Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”
The Migraine–Stroke Connection
Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.
Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.
Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.
Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.
Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.
A Retrospective Cohort Study
Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.
The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).
The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.
Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.
In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.
Prediction Models
In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.
Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.
Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”
—Jake Remaly
Suggested Reading
Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.
Migraineurs are more likely to have an ischemic stroke in the 30 days after surgery, compared with patients without a history of migraine.
Migraineurs are more likely to have an ischemic stroke in the 30 days after surgery, compared with patients without a history of migraine.
ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scienti
“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.
Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”
The Migraine–Stroke Connection
Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.
Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.
Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.
Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.
Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.
A Retrospective Cohort Study
Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.
The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).
The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.
Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.
In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.
Prediction Models
In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.
Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.
Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”
—Jake Remaly
Suggested Reading
Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.
ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scienti
“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.
Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”
The Migraine–Stroke Connection
Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.
Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.
Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.
Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.
Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.
A Retrospective Cohort Study
Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.
The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).
The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.
Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.
In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.
Prediction Models
In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.
Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.
Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”
—Jake Remaly
Suggested Reading
Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.