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Headache after drinking red wine? This could be why
This transcript has been edited for clarity.
Robert Louis Stevenson famously said, “Wine is bottled poetry.” And I think it works quite well. I’ve had wines that are simple, elegant, and unpretentious like Emily Dickinson, and passionate and mysterious like Pablo Neruda. And I’ve had wines that are more analogous to the limerick you might read scrawled on a rest-stop bathroom wall. Those ones give me headaches.
– and apparently it’s not just the alcohol.
Headaches are common, and headaches after drinking alcohol are particularly common. An interesting epidemiologic phenomenon, not yet adequately explained, is why red wine is associated with more headache than other forms of alcohol. There have been many studies fingering many suspects, from sulfites to tannins to various phenolic compounds, but none have really provided a concrete explanation for what might be going on.
A new hypothesis came to the fore on Nov. 20 in the journal Scientific Reports:
To understand the idea, first a reminder of what happens when you drink alcohol, physiologically.
Alcohol is metabolized by the enzyme alcohol dehydrogenase in the gut and then in the liver. That turns it into acetaldehyde, a toxic metabolite. In most of us, aldehyde dehydrogenase (ALDH) quickly metabolizes acetaldehyde to the inert acetate, which can be safely excreted.
I say “most of us” because some populations, particularly those with East Asian ancestry, have a mutation in the ALDH gene which can lead to accumulation of toxic acetaldehyde with alcohol consumption – leading to facial flushing, nausea, and headache.
We can also inhibit the enzyme medically. That’s what the drug disulfiram, also known as Antabuse, does. It doesn’t prevent you from wanting to drink; it makes the consequences of drinking incredibly aversive.
The researchers focused in on the aldehyde dehydrogenase enzyme and conducted a screening study. Are there any compounds in red wine that naturally inhibit ALDH?
The results pointed squarely at quercetin, and particularly its metabolite quercetin glucuronide, which, at 20 micromolar concentrations, inhibited about 80% of ALDH activity.
Quercetin is a flavonoid – a compound that gives color to a variety of vegetables and fruits, including grapes. In a test tube, it is an antioxidant, which is enough evidence to spawn a small quercetin-as-supplement industry, but there is no convincing evidence that it is medically useful. The authors then examined the concentration of quercetin glucuronide to achieve various inhibitions of ALDH, as you can see in this graph here.
By about 10 micromolar, we see a decent amount of inhibition. Disulfiram is about 10 times more potent than that, but then again, you don’t drink three glasses of disulfiram with Thanksgiving dinner.
This is where this study stops. But it obviously tells us very little about what might be happening in the human body. For that, we need to ask the question: Can we get our quercetin levels to 10 micromolar? Is that remotely achievable?
Let’s start with how much quercetin there is in red wine. Like all things wine, it varies, but this study examining Australian wines found mean concentrations of 11 mg/L. The highest value I saw was close to 50 mg/L.
So let’s do some math. To make the numbers easy, let’s say you drank a liter of Australian wine, taking in 50 mg of quercetin glucuronide.
How much of that gets into your bloodstream? Some studies suggest a bioavailability of less than 1%, which basically means none and should probably put the quercetin hypothesis to bed. But there is some variation here too; it seems to depend on the form of quercetin you ingest.
Let’s say all 50 mg gets into your bloodstream. What blood concentration would that lead to? Well, I’ll keep the stoichiometry in the graphics and just say that if we assume that the volume of distribution of the compound is restricted to plasma alone, then you could achieve similar concentrations to what was done in petri dishes during this study.
Of course, if quercetin is really the culprit behind red wine headache, I have some questions: Why aren’t the Amazon reviews of quercetin supplements chock full of warnings not to take them with alcohol? And other foods have way higher quercetin concentration than wine, but you don’t hear people warning not to take your red onions with alcohol, or your capers, or lingonberries.
There’s some more work to be done here – most importantly, some human studies. Let’s give people wine with different amounts of quercetin and see what happens. Sign me up. Seriously.
As for Thanksgiving, it’s worth noting that cranberries have a lot of quercetin in them. So between the cranberry sauce, the Beaujolais, and your uncle ranting about the contrails again, the probability of headache is pretty darn high. Stay safe out there, and Happy Thanksgiving.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Robert Louis Stevenson famously said, “Wine is bottled poetry.” And I think it works quite well. I’ve had wines that are simple, elegant, and unpretentious like Emily Dickinson, and passionate and mysterious like Pablo Neruda. And I’ve had wines that are more analogous to the limerick you might read scrawled on a rest-stop bathroom wall. Those ones give me headaches.
– and apparently it’s not just the alcohol.
Headaches are common, and headaches after drinking alcohol are particularly common. An interesting epidemiologic phenomenon, not yet adequately explained, is why red wine is associated with more headache than other forms of alcohol. There have been many studies fingering many suspects, from sulfites to tannins to various phenolic compounds, but none have really provided a concrete explanation for what might be going on.
A new hypothesis came to the fore on Nov. 20 in the journal Scientific Reports:
To understand the idea, first a reminder of what happens when you drink alcohol, physiologically.
Alcohol is metabolized by the enzyme alcohol dehydrogenase in the gut and then in the liver. That turns it into acetaldehyde, a toxic metabolite. In most of us, aldehyde dehydrogenase (ALDH) quickly metabolizes acetaldehyde to the inert acetate, which can be safely excreted.
I say “most of us” because some populations, particularly those with East Asian ancestry, have a mutation in the ALDH gene which can lead to accumulation of toxic acetaldehyde with alcohol consumption – leading to facial flushing, nausea, and headache.
We can also inhibit the enzyme medically. That’s what the drug disulfiram, also known as Antabuse, does. It doesn’t prevent you from wanting to drink; it makes the consequences of drinking incredibly aversive.
The researchers focused in on the aldehyde dehydrogenase enzyme and conducted a screening study. Are there any compounds in red wine that naturally inhibit ALDH?
The results pointed squarely at quercetin, and particularly its metabolite quercetin glucuronide, which, at 20 micromolar concentrations, inhibited about 80% of ALDH activity.
Quercetin is a flavonoid – a compound that gives color to a variety of vegetables and fruits, including grapes. In a test tube, it is an antioxidant, which is enough evidence to spawn a small quercetin-as-supplement industry, but there is no convincing evidence that it is medically useful. The authors then examined the concentration of quercetin glucuronide to achieve various inhibitions of ALDH, as you can see in this graph here.
By about 10 micromolar, we see a decent amount of inhibition. Disulfiram is about 10 times more potent than that, but then again, you don’t drink three glasses of disulfiram with Thanksgiving dinner.
This is where this study stops. But it obviously tells us very little about what might be happening in the human body. For that, we need to ask the question: Can we get our quercetin levels to 10 micromolar? Is that remotely achievable?
Let’s start with how much quercetin there is in red wine. Like all things wine, it varies, but this study examining Australian wines found mean concentrations of 11 mg/L. The highest value I saw was close to 50 mg/L.
So let’s do some math. To make the numbers easy, let’s say you drank a liter of Australian wine, taking in 50 mg of quercetin glucuronide.
How much of that gets into your bloodstream? Some studies suggest a bioavailability of less than 1%, which basically means none and should probably put the quercetin hypothesis to bed. But there is some variation here too; it seems to depend on the form of quercetin you ingest.
Let’s say all 50 mg gets into your bloodstream. What blood concentration would that lead to? Well, I’ll keep the stoichiometry in the graphics and just say that if we assume that the volume of distribution of the compound is restricted to plasma alone, then you could achieve similar concentrations to what was done in petri dishes during this study.
Of course, if quercetin is really the culprit behind red wine headache, I have some questions: Why aren’t the Amazon reviews of quercetin supplements chock full of warnings not to take them with alcohol? And other foods have way higher quercetin concentration than wine, but you don’t hear people warning not to take your red onions with alcohol, or your capers, or lingonberries.
There’s some more work to be done here – most importantly, some human studies. Let’s give people wine with different amounts of quercetin and see what happens. Sign me up. Seriously.
As for Thanksgiving, it’s worth noting that cranberries have a lot of quercetin in them. So between the cranberry sauce, the Beaujolais, and your uncle ranting about the contrails again, the probability of headache is pretty darn high. Stay safe out there, and Happy Thanksgiving.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Robert Louis Stevenson famously said, “Wine is bottled poetry.” And I think it works quite well. I’ve had wines that are simple, elegant, and unpretentious like Emily Dickinson, and passionate and mysterious like Pablo Neruda. And I’ve had wines that are more analogous to the limerick you might read scrawled on a rest-stop bathroom wall. Those ones give me headaches.
– and apparently it’s not just the alcohol.
Headaches are common, and headaches after drinking alcohol are particularly common. An interesting epidemiologic phenomenon, not yet adequately explained, is why red wine is associated with more headache than other forms of alcohol. There have been many studies fingering many suspects, from sulfites to tannins to various phenolic compounds, but none have really provided a concrete explanation for what might be going on.
A new hypothesis came to the fore on Nov. 20 in the journal Scientific Reports:
To understand the idea, first a reminder of what happens when you drink alcohol, physiologically.
Alcohol is metabolized by the enzyme alcohol dehydrogenase in the gut and then in the liver. That turns it into acetaldehyde, a toxic metabolite. In most of us, aldehyde dehydrogenase (ALDH) quickly metabolizes acetaldehyde to the inert acetate, which can be safely excreted.
I say “most of us” because some populations, particularly those with East Asian ancestry, have a mutation in the ALDH gene which can lead to accumulation of toxic acetaldehyde with alcohol consumption – leading to facial flushing, nausea, and headache.
We can also inhibit the enzyme medically. That’s what the drug disulfiram, also known as Antabuse, does. It doesn’t prevent you from wanting to drink; it makes the consequences of drinking incredibly aversive.
The researchers focused in on the aldehyde dehydrogenase enzyme and conducted a screening study. Are there any compounds in red wine that naturally inhibit ALDH?
The results pointed squarely at quercetin, and particularly its metabolite quercetin glucuronide, which, at 20 micromolar concentrations, inhibited about 80% of ALDH activity.
Quercetin is a flavonoid – a compound that gives color to a variety of vegetables and fruits, including grapes. In a test tube, it is an antioxidant, which is enough evidence to spawn a small quercetin-as-supplement industry, but there is no convincing evidence that it is medically useful. The authors then examined the concentration of quercetin glucuronide to achieve various inhibitions of ALDH, as you can see in this graph here.
By about 10 micromolar, we see a decent amount of inhibition. Disulfiram is about 10 times more potent than that, but then again, you don’t drink three glasses of disulfiram with Thanksgiving dinner.
This is where this study stops. But it obviously tells us very little about what might be happening in the human body. For that, we need to ask the question: Can we get our quercetin levels to 10 micromolar? Is that remotely achievable?
Let’s start with how much quercetin there is in red wine. Like all things wine, it varies, but this study examining Australian wines found mean concentrations of 11 mg/L. The highest value I saw was close to 50 mg/L.
So let’s do some math. To make the numbers easy, let’s say you drank a liter of Australian wine, taking in 50 mg of quercetin glucuronide.
How much of that gets into your bloodstream? Some studies suggest a bioavailability of less than 1%, which basically means none and should probably put the quercetin hypothesis to bed. But there is some variation here too; it seems to depend on the form of quercetin you ingest.
Let’s say all 50 mg gets into your bloodstream. What blood concentration would that lead to? Well, I’ll keep the stoichiometry in the graphics and just say that if we assume that the volume of distribution of the compound is restricted to plasma alone, then you could achieve similar concentrations to what was done in petri dishes during this study.
Of course, if quercetin is really the culprit behind red wine headache, I have some questions: Why aren’t the Amazon reviews of quercetin supplements chock full of warnings not to take them with alcohol? And other foods have way higher quercetin concentration than wine, but you don’t hear people warning not to take your red onions with alcohol, or your capers, or lingonberries.
There’s some more work to be done here – most importantly, some human studies. Let’s give people wine with different amounts of quercetin and see what happens. Sign me up. Seriously.
As for Thanksgiving, it’s worth noting that cranberries have a lot of quercetin in them. So between the cranberry sauce, the Beaujolais, and your uncle ranting about the contrails again, the probability of headache is pretty darn high. Stay safe out there, and Happy Thanksgiving.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Adolescents with migraine need smooth handoff to adult care
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Memory-enhancing intervention may help boost confidence, not necessarily memory, in older adults, study suggests
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM GSA 2023
Avoid adding to minority stress when treating headache in LGBTQIA+ patients
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Hourly air pollution exposure: A risk factor for stroke
TOPLINE:
METHODOLOGY:
- Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
- The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
- Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
- Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.
TAKEAWAY:
- Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
- Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
- Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.
IN PRACTICE:
“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.
SOURCE:
The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.
LIMITATIONS:
- Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
- There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.
DISCLOSURES:
This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
- The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
- Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
- Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.
TAKEAWAY:
- Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
- Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
- Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.
IN PRACTICE:
“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.
SOURCE:
The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.
LIMITATIONS:
- Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
- There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.
DISCLOSURES:
This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
- The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
- Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
- Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.
TAKEAWAY:
- Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
- Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
- Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.
IN PRACTICE:
“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.
SOURCE:
The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.
LIMITATIONS:
- Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
- There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.
DISCLOSURES:
This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.
A version of this article first appeared on Medscape.com.
Fibromyalgia, CFS more prevalent in patients with IBS
TOPLINE:
METHODOLOGY:
- The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
- The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
- A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
- Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).
TAKEAWAY:
- Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
- The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
- IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
- Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
- Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.
IN PRACTICE:
“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.
SOURCE:
Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.
LIMITATIONS:
The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.
DISCLOSURES:
The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
TOPLINE:
METHODOLOGY:
- The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
- The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
- A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
- Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).
TAKEAWAY:
- Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
- The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
- IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
- Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
- Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.
IN PRACTICE:
“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.
SOURCE:
Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.
LIMITATIONS:
The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.
DISCLOSURES:
The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
TOPLINE:
METHODOLOGY:
- The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
- The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
- A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
- Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).
TAKEAWAY:
- Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
- The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
- IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
- Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
- Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.
IN PRACTICE:
“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.
SOURCE:
Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.
LIMITATIONS:
The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.
DISCLOSURES:
The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
Spinal cord stimulator restores Parkinson patient’s gait
The neuroprosthesis involves targeted epidural electrical stimulation of areas of the lumbosacral spinal cord that produce walking.
This new therapeutic tool offers hope to patients with PD and, combined with existing approaches, may alleviate a motor sign in PD for which there is currently “no real solution,” study investigator Eduardo Martin Moraud, PhD, who leads PD research at the Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland, said in an interview.
“This is exciting for the many patients that develop gait deficits and experience frequent falls, who can only rely on physical therapy to try and minimize the consequences,” he added.
The findings were published online in Nature Medicine.
Personalized stimulation
About 90% of people with advanced PD experience gait and balance problems or freezing-of-gait episodes. These locomotor deficits typically don’t respond well to dopamine replacement therapy or deep brain stimulation (DBS) of the subthalamic nucleus, possibly because the neural origins of these motor problems involve brain circuits not related to dopamine, said Dr. Moraud.
Continuous electrical stimulation over the cervical or thoracic segments of the spinal cord reduces locomotor deficits in some people with PD, but the broader application of this strategy has led to variable and unsatisfying outcomes.
The new approach focuses on correcting abnormal activation of circuits in the lumbar spinal cord, a region that hosts all the neurons that control activation of the leg muscles used for walking.
The stimulating device is placed on the lumbar region of the spinal cord, which sends messages to leg muscles. It is wired to a small impulse generator implanted under the skin of the abdomen. Sensors placed in shoes align the stimulation to the patient’s movement.
The system can detect the beginning of a movement, immediately activate the appropriate electrode, and so facilitate the necessary movement, be that leg flexion, extension, or propulsion, said Dr. Moraud. “This allows for increased walking symmetry, reinforced balance, and increased length of steps.”
The concept of this neuroprosthesis is similar to that used to allow patients with a spinal cord injury (SCI) to walk. But unlike patients with SCI, those with PD can move their legs, indicating that there is a descending command from the brain that needs to interact with the stimulation of the spinal cord, and patients with PD can feel the stimulation.
“Both these elements imply that amplitudes of stimulation need to be much lower in PD than SCI, and that stimulation needs to be fully personalized in PD to synergistically interact with the descending commands from the brain.”
After fine-tuning this new neuroprosthesis in animal models, researchers implanted the device in a 62-year-old man with a 30-year history of PD who presented with severe gait impairments, including marked gait asymmetry, reduced stride length, and balance problems.
Gait restored to near normal
The patient had frequent freezing-of-gait episodes when turning and passing through narrow paths, which led to multiple falls a day. This was despite being treated with DBS and dopaminergic replacement therapies.
But after getting used to the neuroprosthesis, the patient now walks with a gait akin to that of people without PD.
“Our experience in the preclinical animal models and this first patient is that gait can be restored to an almost healthy level, but this, of course, may vary across patients, depending on the severity of their disease progression, and their other motor deficits,” said Dr. Moraud.
When the neuroprosthesis is turned on, freezing of gait nearly vanishes, both with and without DBS.
In addition, the neuroprosthesis augmented the impact of the patient’s rehabilitation program, which involved a variety of regular exercises, including walking on basic and complex terrains, navigating outdoors in community settings, balance training, and basic physical therapy.
Frequent use of the neuroprosthesis during gait rehabilitation also translated into “highly improved” quality of life as reported by the patient (and his wife), said Dr. Moraud.
The patient has now been using the neuroprosthesis about 8 hours a day for nearly 2 years, only switching it off when sitting for long periods of time or while sleeping.
“He regained the capacity to walk in complex or crowded environments such as shops, airports, or his own home, without falling,” said Dr. Moraud. “He went from falling five to six times per day to one or two [falls] every couple of weeks. He’s also much more confident. He can walk for many miles, run, and go on holidays, without the constant fear of falling and having related injuries.”
Dr. Moraud stressed that the device does not replace DBS, which is a “key therapy” that addresses other deficits in PD, such as rigidity or slowness of movement. “What we propose here is a fully complementary approach for the gait problems that are not well addressed by DBS.”
One of the next steps will be to evaluate the efficacy of this approach across a wider spectrum of patient profiles to fully define the best responders, said Dr. Moraud.
A ‘tour de force’
In a comment, Michael S. Okun, MD, director of the Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, and medical director of the Parkinson’s Foundation, noted that the researchers used “a smarter device” than past approaches that failed to adequately address progressive walking challenges of patients with PD.
Although it’s “tempting to get excited” about the findings, it’s important to consider that the study included only one human subject and did not target circuits for both walking and balance, said Dr. Okun. “It’s possible that even if future studies revealed a benefit for walking, the device may or may not address falling.”
In an accompanying editorial, Aviv Mizrahi-Kliger, MD, PhD, department of neurology, University of California, San Francisco, and Karunesh Ganguly, MD, PhD, Neurology and Rehabilitation Service, San Francisco Veterans Affairs Health Care System, called the study an “impressive tour de force,” with data from the nonhuman primate model and the individual with PD “jointly” indicating that epidural electrical stimulation (EES) “is a very promising treatment for several aspects of gait, posture and balance impairments in PD.”
But although the effect in the single patient “is quite impressive,” the “next crucial step” is to test this approach in a larger cohort of patients, they said.
They noted the nonhuman model does not exhibit freezing of gait, “which precluded the ability to corroborate or further study the role of EES in alleviating this symptom of PD in an animal model.”
In addition, stimulation parameters in the patient with PD “had to rely on estimated normal activity patterns, owing to the inability to measure pre-disease patterns at the individual level,” they wrote.
The study received funding from the Defitech Foundation, ONWARD Medical, CAMS Innovation Fund for Medical Sciences, National Natural Science Foundation of China, Parkinson Schweiz Foundation, European Community’s Seventh Framework Program (NeuWalk), European Research Council, Wyss Center for Bio and Neuroengineering, Bertarelli Foundation, and Swiss National Science Foundation. Dr. Moraud and other study authors hold various patents or applications in relation to the present work. Dr. Mizrahi-Kliger has no relevant conflicts of interest; Dr. Ganguly has a patent for modulation of sensory inputs to improve motor recovery from stroke and has been a consultant to Cala Health.
A version of this article first appeared on Medscape.com.
The neuroprosthesis involves targeted epidural electrical stimulation of areas of the lumbosacral spinal cord that produce walking.
This new therapeutic tool offers hope to patients with PD and, combined with existing approaches, may alleviate a motor sign in PD for which there is currently “no real solution,” study investigator Eduardo Martin Moraud, PhD, who leads PD research at the Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland, said in an interview.
“This is exciting for the many patients that develop gait deficits and experience frequent falls, who can only rely on physical therapy to try and minimize the consequences,” he added.
The findings were published online in Nature Medicine.
Personalized stimulation
About 90% of people with advanced PD experience gait and balance problems or freezing-of-gait episodes. These locomotor deficits typically don’t respond well to dopamine replacement therapy or deep brain stimulation (DBS) of the subthalamic nucleus, possibly because the neural origins of these motor problems involve brain circuits not related to dopamine, said Dr. Moraud.
Continuous electrical stimulation over the cervical or thoracic segments of the spinal cord reduces locomotor deficits in some people with PD, but the broader application of this strategy has led to variable and unsatisfying outcomes.
The new approach focuses on correcting abnormal activation of circuits in the lumbar spinal cord, a region that hosts all the neurons that control activation of the leg muscles used for walking.
The stimulating device is placed on the lumbar region of the spinal cord, which sends messages to leg muscles. It is wired to a small impulse generator implanted under the skin of the abdomen. Sensors placed in shoes align the stimulation to the patient’s movement.
The system can detect the beginning of a movement, immediately activate the appropriate electrode, and so facilitate the necessary movement, be that leg flexion, extension, or propulsion, said Dr. Moraud. “This allows for increased walking symmetry, reinforced balance, and increased length of steps.”
The concept of this neuroprosthesis is similar to that used to allow patients with a spinal cord injury (SCI) to walk. But unlike patients with SCI, those with PD can move their legs, indicating that there is a descending command from the brain that needs to interact with the stimulation of the spinal cord, and patients with PD can feel the stimulation.
“Both these elements imply that amplitudes of stimulation need to be much lower in PD than SCI, and that stimulation needs to be fully personalized in PD to synergistically interact with the descending commands from the brain.”
After fine-tuning this new neuroprosthesis in animal models, researchers implanted the device in a 62-year-old man with a 30-year history of PD who presented with severe gait impairments, including marked gait asymmetry, reduced stride length, and balance problems.
Gait restored to near normal
The patient had frequent freezing-of-gait episodes when turning and passing through narrow paths, which led to multiple falls a day. This was despite being treated with DBS and dopaminergic replacement therapies.
But after getting used to the neuroprosthesis, the patient now walks with a gait akin to that of people without PD.
“Our experience in the preclinical animal models and this first patient is that gait can be restored to an almost healthy level, but this, of course, may vary across patients, depending on the severity of their disease progression, and their other motor deficits,” said Dr. Moraud.
When the neuroprosthesis is turned on, freezing of gait nearly vanishes, both with and without DBS.
In addition, the neuroprosthesis augmented the impact of the patient’s rehabilitation program, which involved a variety of regular exercises, including walking on basic and complex terrains, navigating outdoors in community settings, balance training, and basic physical therapy.
Frequent use of the neuroprosthesis during gait rehabilitation also translated into “highly improved” quality of life as reported by the patient (and his wife), said Dr. Moraud.
The patient has now been using the neuroprosthesis about 8 hours a day for nearly 2 years, only switching it off when sitting for long periods of time or while sleeping.
“He regained the capacity to walk in complex or crowded environments such as shops, airports, or his own home, without falling,” said Dr. Moraud. “He went from falling five to six times per day to one or two [falls] every couple of weeks. He’s also much more confident. He can walk for many miles, run, and go on holidays, without the constant fear of falling and having related injuries.”
Dr. Moraud stressed that the device does not replace DBS, which is a “key therapy” that addresses other deficits in PD, such as rigidity or slowness of movement. “What we propose here is a fully complementary approach for the gait problems that are not well addressed by DBS.”
One of the next steps will be to evaluate the efficacy of this approach across a wider spectrum of patient profiles to fully define the best responders, said Dr. Moraud.
A ‘tour de force’
In a comment, Michael S. Okun, MD, director of the Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, and medical director of the Parkinson’s Foundation, noted that the researchers used “a smarter device” than past approaches that failed to adequately address progressive walking challenges of patients with PD.
Although it’s “tempting to get excited” about the findings, it’s important to consider that the study included only one human subject and did not target circuits for both walking and balance, said Dr. Okun. “It’s possible that even if future studies revealed a benefit for walking, the device may or may not address falling.”
In an accompanying editorial, Aviv Mizrahi-Kliger, MD, PhD, department of neurology, University of California, San Francisco, and Karunesh Ganguly, MD, PhD, Neurology and Rehabilitation Service, San Francisco Veterans Affairs Health Care System, called the study an “impressive tour de force,” with data from the nonhuman primate model and the individual with PD “jointly” indicating that epidural electrical stimulation (EES) “is a very promising treatment for several aspects of gait, posture and balance impairments in PD.”
But although the effect in the single patient “is quite impressive,” the “next crucial step” is to test this approach in a larger cohort of patients, they said.
They noted the nonhuman model does not exhibit freezing of gait, “which precluded the ability to corroborate or further study the role of EES in alleviating this symptom of PD in an animal model.”
In addition, stimulation parameters in the patient with PD “had to rely on estimated normal activity patterns, owing to the inability to measure pre-disease patterns at the individual level,” they wrote.
The study received funding from the Defitech Foundation, ONWARD Medical, CAMS Innovation Fund for Medical Sciences, National Natural Science Foundation of China, Parkinson Schweiz Foundation, European Community’s Seventh Framework Program (NeuWalk), European Research Council, Wyss Center for Bio and Neuroengineering, Bertarelli Foundation, and Swiss National Science Foundation. Dr. Moraud and other study authors hold various patents or applications in relation to the present work. Dr. Mizrahi-Kliger has no relevant conflicts of interest; Dr. Ganguly has a patent for modulation of sensory inputs to improve motor recovery from stroke and has been a consultant to Cala Health.
A version of this article first appeared on Medscape.com.
The neuroprosthesis involves targeted epidural electrical stimulation of areas of the lumbosacral spinal cord that produce walking.
This new therapeutic tool offers hope to patients with PD and, combined with existing approaches, may alleviate a motor sign in PD for which there is currently “no real solution,” study investigator Eduardo Martin Moraud, PhD, who leads PD research at the Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland, said in an interview.
“This is exciting for the many patients that develop gait deficits and experience frequent falls, who can only rely on physical therapy to try and minimize the consequences,” he added.
The findings were published online in Nature Medicine.
Personalized stimulation
About 90% of people with advanced PD experience gait and balance problems or freezing-of-gait episodes. These locomotor deficits typically don’t respond well to dopamine replacement therapy or deep brain stimulation (DBS) of the subthalamic nucleus, possibly because the neural origins of these motor problems involve brain circuits not related to dopamine, said Dr. Moraud.
Continuous electrical stimulation over the cervical or thoracic segments of the spinal cord reduces locomotor deficits in some people with PD, but the broader application of this strategy has led to variable and unsatisfying outcomes.
The new approach focuses on correcting abnormal activation of circuits in the lumbar spinal cord, a region that hosts all the neurons that control activation of the leg muscles used for walking.
The stimulating device is placed on the lumbar region of the spinal cord, which sends messages to leg muscles. It is wired to a small impulse generator implanted under the skin of the abdomen. Sensors placed in shoes align the stimulation to the patient’s movement.
The system can detect the beginning of a movement, immediately activate the appropriate electrode, and so facilitate the necessary movement, be that leg flexion, extension, or propulsion, said Dr. Moraud. “This allows for increased walking symmetry, reinforced balance, and increased length of steps.”
The concept of this neuroprosthesis is similar to that used to allow patients with a spinal cord injury (SCI) to walk. But unlike patients with SCI, those with PD can move their legs, indicating that there is a descending command from the brain that needs to interact with the stimulation of the spinal cord, and patients with PD can feel the stimulation.
“Both these elements imply that amplitudes of stimulation need to be much lower in PD than SCI, and that stimulation needs to be fully personalized in PD to synergistically interact with the descending commands from the brain.”
After fine-tuning this new neuroprosthesis in animal models, researchers implanted the device in a 62-year-old man with a 30-year history of PD who presented with severe gait impairments, including marked gait asymmetry, reduced stride length, and balance problems.
Gait restored to near normal
The patient had frequent freezing-of-gait episodes when turning and passing through narrow paths, which led to multiple falls a day. This was despite being treated with DBS and dopaminergic replacement therapies.
But after getting used to the neuroprosthesis, the patient now walks with a gait akin to that of people without PD.
“Our experience in the preclinical animal models and this first patient is that gait can be restored to an almost healthy level, but this, of course, may vary across patients, depending on the severity of their disease progression, and their other motor deficits,” said Dr. Moraud.
When the neuroprosthesis is turned on, freezing of gait nearly vanishes, both with and without DBS.
In addition, the neuroprosthesis augmented the impact of the patient’s rehabilitation program, which involved a variety of regular exercises, including walking on basic and complex terrains, navigating outdoors in community settings, balance training, and basic physical therapy.
Frequent use of the neuroprosthesis during gait rehabilitation also translated into “highly improved” quality of life as reported by the patient (and his wife), said Dr. Moraud.
The patient has now been using the neuroprosthesis about 8 hours a day for nearly 2 years, only switching it off when sitting for long periods of time or while sleeping.
“He regained the capacity to walk in complex or crowded environments such as shops, airports, or his own home, without falling,” said Dr. Moraud. “He went from falling five to six times per day to one or two [falls] every couple of weeks. He’s also much more confident. He can walk for many miles, run, and go on holidays, without the constant fear of falling and having related injuries.”
Dr. Moraud stressed that the device does not replace DBS, which is a “key therapy” that addresses other deficits in PD, such as rigidity or slowness of movement. “What we propose here is a fully complementary approach for the gait problems that are not well addressed by DBS.”
One of the next steps will be to evaluate the efficacy of this approach across a wider spectrum of patient profiles to fully define the best responders, said Dr. Moraud.
A ‘tour de force’
In a comment, Michael S. Okun, MD, director of the Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, and medical director of the Parkinson’s Foundation, noted that the researchers used “a smarter device” than past approaches that failed to adequately address progressive walking challenges of patients with PD.
Although it’s “tempting to get excited” about the findings, it’s important to consider that the study included only one human subject and did not target circuits for both walking and balance, said Dr. Okun. “It’s possible that even if future studies revealed a benefit for walking, the device may or may not address falling.”
In an accompanying editorial, Aviv Mizrahi-Kliger, MD, PhD, department of neurology, University of California, San Francisco, and Karunesh Ganguly, MD, PhD, Neurology and Rehabilitation Service, San Francisco Veterans Affairs Health Care System, called the study an “impressive tour de force,” with data from the nonhuman primate model and the individual with PD “jointly” indicating that epidural electrical stimulation (EES) “is a very promising treatment for several aspects of gait, posture and balance impairments in PD.”
But although the effect in the single patient “is quite impressive,” the “next crucial step” is to test this approach in a larger cohort of patients, they said.
They noted the nonhuman model does not exhibit freezing of gait, “which precluded the ability to corroborate or further study the role of EES in alleviating this symptom of PD in an animal model.”
In addition, stimulation parameters in the patient with PD “had to rely on estimated normal activity patterns, owing to the inability to measure pre-disease patterns at the individual level,” they wrote.
The study received funding from the Defitech Foundation, ONWARD Medical, CAMS Innovation Fund for Medical Sciences, National Natural Science Foundation of China, Parkinson Schweiz Foundation, European Community’s Seventh Framework Program (NeuWalk), European Research Council, Wyss Center for Bio and Neuroengineering, Bertarelli Foundation, and Swiss National Science Foundation. Dr. Moraud and other study authors hold various patents or applications in relation to the present work. Dr. Mizrahi-Kliger has no relevant conflicts of interest; Dr. Ganguly has a patent for modulation of sensory inputs to improve motor recovery from stroke and has been a consultant to Cala Health.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
Atrial fibrillation linked to dementia, especially when diagnosed before age 65 years
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Blood test could predict future disability in MS
a new study suggests.
Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.
This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.
“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.
The findings were published online in JAMA Neurology.
Early warning system?
The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).
Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.
Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.
Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.
Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).
The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).
The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.
“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
Challenges for clinicians
Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.
“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.
“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”
The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.
“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said
The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.
A version of this article appeared on Medscape.com.
a new study suggests.
Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.
This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.
“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.
The findings were published online in JAMA Neurology.
Early warning system?
The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).
Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.
Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.
Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.
Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).
The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).
The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.
“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
Challenges for clinicians
Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.
“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.
“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”
The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.
“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said
The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.
A version of this article appeared on Medscape.com.
a new study suggests.
Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.
This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.
“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.
The findings were published online in JAMA Neurology.
Early warning system?
The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).
Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.
Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.
Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.
Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).
The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).
The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.
“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
Challenges for clinicians
Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.
“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.
“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”
The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.
“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said
The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.
A version of this article appeared on Medscape.com.
FROM JAMA NEUROLOGY
Short steroid taper tested with tocilizumab for giant cell arteritis
TOPLINE:
A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).
METHODOLOGY:
- In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
- Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
- The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.
TAKEAWAY:
- At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
- Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
- The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
- All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.
IN PRACTICE:
Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.
SOURCE:
The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .
LIMITATIONS:
The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.
DISCLOSURES:
The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.
A version of this article first appeared on Medscape.com.
TOPLINE:
A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).
METHODOLOGY:
- In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
- Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
- The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.
TAKEAWAY:
- At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
- Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
- The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
- All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.
IN PRACTICE:
Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.
SOURCE:
The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .
LIMITATIONS:
The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.
DISCLOSURES:
The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.
A version of this article first appeared on Medscape.com.
TOPLINE:
A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).
METHODOLOGY:
- In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
- Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
- The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.
TAKEAWAY:
- At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
- Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
- The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
- All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.
IN PRACTICE:
Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.
SOURCE:
The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .
LIMITATIONS:
The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.
DISCLOSURES:
The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.
A version of this article first appeared on Medscape.com.