Neurology

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

A version of this article first appeared on Medscape.com.

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

A version of this article first appeared on Medscape.com.

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

A version of this article first appeared on Medscape.com.

Alcohol is the most common substance misused by veterans. ¹ Veterans may m isuse alcohol as a result of mental illness or posttraumatic stress disorder (PTSD), having difficulties adjusting to civilian life, or because of heavy drinking habits acquired before leaving active duty. ² One potential long-term effect of chronic alcohol misuse is Wernicke-Korsakoff syndrome (WKS), a neuropsychiatric condition secondary to a deficiency of thiamine. ³ The disease is characterized by altered mental status, oculomotor findings, and ataxia. ³ Patients with WKS may exhibit challenging behaviors, including aggression, disinhibition, and lack of awareness of their illness. ⁴ Due to long-standing cognitive and physical deficits, many patients require lifelong care with a focus on a palliative approach. ³

The mainstay of pharmacologic management for the neuropsychiatric symptoms of WKS continues to be psychoactive medications, such as antipsychotics, benzodiazepines, antidepressants, and anticonvulsant medications.^4-6 Though atypical antipsychotic medications remain the most widely used, they have a high adverse effect (AE) profile.^5,6 Among the potential AEs are metabolic syndrome, anticholinergic effects, QTc prolongation, orthostatic hypotension, extrapyramidal effects, sedation, and falls. There also is a US Food and Drug Administration boxed warning for increased risk of mortality.⁷ With the goal of improving and maintaining patient safety, pharmacologic interventions with lower AEs may be beneficial in the management of the neuropsychiatric symptoms of WKS.

This case describes a veteran who was initially hospitalized due to confusion, ataxia, and nystagmus secondary to chronic alcohol overuse. The aim of the case was to consider the use of acetaminophen in place of psychoactive medications as a way to manage neuropsychiatric symptoms of WKS even when pain was not present.

Case Presentation

A veteran presented to the local US Department of Veterans Affairs (VA) emergency department (ED) due to their spouse’s concern of acute onset confusion and ambulatory difficulties. The veteran’s medical history included extensive alcohol misuse, mild asthma, and diet-controlled hyperlipidemia. On initial evaluation, the veteran displayed symptoms of ataxia and confusion. When asked why the veteran was at the ED, the response was, “I just came to the hospital to find my sister.” Based on their medical history, clinical evaluation, and altered mental status, the veteran was admitted to the acute care medical service with a presumptive diagnosis of WKS.

On admission, the laboratory evaluation revealed normal alanine transaminase (ALT) and aspartate transaminase (AST) levels but markedly elevated γ-glutamyl transferase (GGT) consistent with alcohol toxicity. COVID-19 testing was negative. Magnetic resonance imaging (MRI) of the brain revealed evidence of alterations in the mammillary bodies and moderately severe cortical and cerebellar volume loss suggestive of long-standing alcohol use.

The veteran was hospitalized for 12 days and treated with high-dose IV thiamine, which resulted in improvement of their ophthalmic disorder (nystagmus) and ataxia. However, they continued to exhibit poor recall, confusion, and occasional agitation characterized by verbal outbursts and aggression toward the staff.

The veteran’s spouse worked full time and did not feel capable of providing the necessary follow-up care at home. The safest discharge plan found was to transfer the veteran to the local VA community living center (CLC) for physical therapy and further support of their marked cognitive decline and agitation.

Following admission to the CLC, the veteran was placed in a secured memory unit with staff trained specifically on management of veterans with cognitive impairment and behavioral concerns. As the veteran did not have decisional capacity on admission, the staff arranged a meeting with the spouse. Based on that conversation, the goals of care were to focus on a palliative approach and the hope that the veteran would one day be able to return home to their spouse.

At the CLC, the veteran was initially treated with thiamine 200 mg orally once daily and albuterol inhaler as needed. A clinical psychologist performed a comprehensive psychological evaluation on admission, which confirmed evidence of WKS with symptoms, including confusion, disorientation, and confabulation. There was no evidence of cultural diversity factors regarding the veteran’s delusional beliefs.

Discussion

Alcohol misuse is a common finding in many US veterans, as well as in the general population.^1,3 As a result, it is not uncommon to see patients with physical and psychological symptoms related to this abuse. Many of these patients will become verbally and physically abusive, thus having appropriate pharmacologic and nonpharmacologic interventions is important.

In this case study, the veteran was diagnosed with WKS and exhibited physical, cognitive, and emotional symptoms consistent with this disease. Although the physical symptoms improved with thiamine and abstinence from alcohol, their cognitive impairment, verbal outbursts, and aggressive demeanor persisted.

After using antipsychotic and anxiolytic medications with minimal clinical improvement, a trial of acetaminophen 650 mg 3 times daily was instituted. The patient’s behavior improved; demeanor became calmer, and they were easily redirected by the nursing staff. Psychological support was again employed, which enhanced and supported the veteran’s calmer demeanor. Although there is limited medical literature on the use of acetaminophen in clinical situations not related to pain, there has been research documenting its effect on social interaction.^9,10

Acetaminophen is an analgesic medication that acts through central neural mechanisms. It has been hypothesized that social and physical pain rely on shared neurochemical underpinnings, and some of the regions of the brain involved in affective experience of physical pain also have been found to be involved in the experience of social pain.¹¹ Acetaminophen may impact an individual’s social well-being as social pain processes.¹¹ It has been shown to blunt reactivity to both physical pain as well as negative stimuli.¹¹

Conclusions

A 2019 survey on alcohol and drug use found 5.6% of adults aged ≥ 18 have an alcohol use disorder.¹² In severe cases, this can result in WKS. Although replacement of thiamine is critical for physical improvement, psychological deficits may persist. Small studies have advanced the concept of using scheduled acetaminophen even when the patient is not verbalizing or displaying pain.¹³ Although more research needs to be done on this topic, this palliative approach may be worth considering, especially if the risks of antipsychotics and anxiolytics outweigh the benefits.

Alcohol is the most common substance misused by veterans. ¹ Veterans may m isuse alcohol as a result of mental illness or posttraumatic stress disorder (PTSD), having difficulties adjusting to civilian life, or because of heavy drinking habits acquired before leaving active duty. ² One potential long-term effect of chronic alcohol misuse is Wernicke-Korsakoff syndrome (WKS), a neuropsychiatric condition secondary to a deficiency of thiamine. ³ The disease is characterized by altered mental status, oculomotor findings, and ataxia. ³ Patients with WKS may exhibit challenging behaviors, including aggression, disinhibition, and lack of awareness of their illness. ⁴ Due to long-standing cognitive and physical deficits, many patients require lifelong care with a focus on a palliative approach. ³

The mainstay of pharmacologic management for the neuropsychiatric symptoms of WKS continues to be psychoactive medications, such as antipsychotics, benzodiazepines, antidepressants, and anticonvulsant medications.^4-6 Though atypical antipsychotic medications remain the most widely used, they have a high adverse effect (AE) profile.^5,6 Among the potential AEs are metabolic syndrome, anticholinergic effects, QTc prolongation, orthostatic hypotension, extrapyramidal effects, sedation, and falls. There also is a US Food and Drug Administration boxed warning for increased risk of mortality.⁷ With the goal of improving and maintaining patient safety, pharmacologic interventions with lower AEs may be beneficial in the management of the neuropsychiatric symptoms of WKS.

This case describes a veteran who was initially hospitalized due to confusion, ataxia, and nystagmus secondary to chronic alcohol overuse. The aim of the case was to consider the use of acetaminophen in place of psychoactive medications as a way to manage neuropsychiatric symptoms of WKS even when pain was not present.

Case Presentation

A veteran presented to the local US Department of Veterans Affairs (VA) emergency department (ED) due to their spouse’s concern of acute onset confusion and ambulatory difficulties. The veteran’s medical history included extensive alcohol misuse, mild asthma, and diet-controlled hyperlipidemia. On initial evaluation, the veteran displayed symptoms of ataxia and confusion. When asked why the veteran was at the ED, the response was, “I just came to the hospital to find my sister.” Based on their medical history, clinical evaluation, and altered mental status, the veteran was admitted to the acute care medical service with a presumptive diagnosis of WKS.

On admission, the laboratory evaluation revealed normal alanine transaminase (ALT) and aspartate transaminase (AST) levels but markedly elevated γ-glutamyl transferase (GGT) consistent with alcohol toxicity. COVID-19 testing was negative. Magnetic resonance imaging (MRI) of the brain revealed evidence of alterations in the mammillary bodies and moderately severe cortical and cerebellar volume loss suggestive of long-standing alcohol use.

The veteran was hospitalized for 12 days and treated with high-dose IV thiamine, which resulted in improvement of their ophthalmic disorder (nystagmus) and ataxia. However, they continued to exhibit poor recall, confusion, and occasional agitation characterized by verbal outbursts and aggression toward the staff.

The veteran’s spouse worked full time and did not feel capable of providing the necessary follow-up care at home. The safest discharge plan found was to transfer the veteran to the local VA community living center (CLC) for physical therapy and further support of their marked cognitive decline and agitation.

Following admission to the CLC, the veteran was placed in a secured memory unit with staff trained specifically on management of veterans with cognitive impairment and behavioral concerns. As the veteran did not have decisional capacity on admission, the staff arranged a meeting with the spouse. Based on that conversation, the goals of care were to focus on a palliative approach and the hope that the veteran would one day be able to return home to their spouse.

At the CLC, the veteran was initially treated with thiamine 200 mg orally once daily and albuterol inhaler as needed. A clinical psychologist performed a comprehensive psychological evaluation on admission, which confirmed evidence of WKS with symptoms, including confusion, disorientation, and confabulation. There was no evidence of cultural diversity factors regarding the veteran’s delusional beliefs.

Discussion

Alcohol misuse is a common finding in many US veterans, as well as in the general population.^1,3 As a result, it is not uncommon to see patients with physical and psychological symptoms related to this abuse. Many of these patients will become verbally and physically abusive, thus having appropriate pharmacologic and nonpharmacologic interventions is important.

In this case study, the veteran was diagnosed with WKS and exhibited physical, cognitive, and emotional symptoms consistent with this disease. Although the physical symptoms improved with thiamine and abstinence from alcohol, their cognitive impairment, verbal outbursts, and aggressive demeanor persisted.

After using antipsychotic and anxiolytic medications with minimal clinical improvement, a trial of acetaminophen 650 mg 3 times daily was instituted. The patient’s behavior improved; demeanor became calmer, and they were easily redirected by the nursing staff. Psychological support was again employed, which enhanced and supported the veteran’s calmer demeanor. Although there is limited medical literature on the use of acetaminophen in clinical situations not related to pain, there has been research documenting its effect on social interaction.^9,10

Acetaminophen is an analgesic medication that acts through central neural mechanisms. It has been hypothesized that social and physical pain rely on shared neurochemical underpinnings, and some of the regions of the brain involved in affective experience of physical pain also have been found to be involved in the experience of social pain.¹¹ Acetaminophen may impact an individual’s social well-being as social pain processes.¹¹ It has been shown to blunt reactivity to both physical pain as well as negative stimuli.¹¹

Conclusions

A 2019 survey on alcohol and drug use found 5.6% of adults aged ≥ 18 have an alcohol use disorder.¹² In severe cases, this can result in WKS. Although replacement of thiamine is critical for physical improvement, psychological deficits may persist. Small studies have advanced the concept of using scheduled acetaminophen even when the patient is not verbalizing or displaying pain.¹³ Although more research needs to be done on this topic, this palliative approach may be worth considering, especially if the risks of antipsychotics and anxiolytics outweigh the benefits.

Alcohol is the most common substance misused by veterans. ¹ Veterans may m isuse alcohol as a result of mental illness or posttraumatic stress disorder (PTSD), having difficulties adjusting to civilian life, or because of heavy drinking habits acquired before leaving active duty. ² One potential long-term effect of chronic alcohol misuse is Wernicke-Korsakoff syndrome (WKS), a neuropsychiatric condition secondary to a deficiency of thiamine. ³ The disease is characterized by altered mental status, oculomotor findings, and ataxia. ³ Patients with WKS may exhibit challenging behaviors, including aggression, disinhibition, and lack of awareness of their illness. ⁴ Due to long-standing cognitive and physical deficits, many patients require lifelong care with a focus on a palliative approach. ³

The mainstay of pharmacologic management for the neuropsychiatric symptoms of WKS continues to be psychoactive medications, such as antipsychotics, benzodiazepines, antidepressants, and anticonvulsant medications.^4-6 Though atypical antipsychotic medications remain the most widely used, they have a high adverse effect (AE) profile.^5,6 Among the potential AEs are metabolic syndrome, anticholinergic effects, QTc prolongation, orthostatic hypotension, extrapyramidal effects, sedation, and falls. There also is a US Food and Drug Administration boxed warning for increased risk of mortality.⁷ With the goal of improving and maintaining patient safety, pharmacologic interventions with lower AEs may be beneficial in the management of the neuropsychiatric symptoms of WKS.

This case describes a veteran who was initially hospitalized due to confusion, ataxia, and nystagmus secondary to chronic alcohol overuse. The aim of the case was to consider the use of acetaminophen in place of psychoactive medications as a way to manage neuropsychiatric symptoms of WKS even when pain was not present.

Case Presentation

A veteran presented to the local US Department of Veterans Affairs (VA) emergency department (ED) due to their spouse’s concern of acute onset confusion and ambulatory difficulties. The veteran’s medical history included extensive alcohol misuse, mild asthma, and diet-controlled hyperlipidemia. On initial evaluation, the veteran displayed symptoms of ataxia and confusion. When asked why the veteran was at the ED, the response was, “I just came to the hospital to find my sister.” Based on their medical history, clinical evaluation, and altered mental status, the veteran was admitted to the acute care medical service with a presumptive diagnosis of WKS.

On admission, the laboratory evaluation revealed normal alanine transaminase (ALT) and aspartate transaminase (AST) levels but markedly elevated γ-glutamyl transferase (GGT) consistent with alcohol toxicity. COVID-19 testing was negative. Magnetic resonance imaging (MRI) of the brain revealed evidence of alterations in the mammillary bodies and moderately severe cortical and cerebellar volume loss suggestive of long-standing alcohol use.

The veteran was hospitalized for 12 days and treated with high-dose IV thiamine, which resulted in improvement of their ophthalmic disorder (nystagmus) and ataxia. However, they continued to exhibit poor recall, confusion, and occasional agitation characterized by verbal outbursts and aggression toward the staff.

The veteran’s spouse worked full time and did not feel capable of providing the necessary follow-up care at home. The safest discharge plan found was to transfer the veteran to the local VA community living center (CLC) for physical therapy and further support of their marked cognitive decline and agitation.

Following admission to the CLC, the veteran was placed in a secured memory unit with staff trained specifically on management of veterans with cognitive impairment and behavioral concerns. As the veteran did not have decisional capacity on admission, the staff arranged a meeting with the spouse. Based on that conversation, the goals of care were to focus on a palliative approach and the hope that the veteran would one day be able to return home to their spouse.

At the CLC, the veteran was initially treated with thiamine 200 mg orally once daily and albuterol inhaler as needed. A clinical psychologist performed a comprehensive psychological evaluation on admission, which confirmed evidence of WKS with symptoms, including confusion, disorientation, and confabulation. There was no evidence of cultural diversity factors regarding the veteran’s delusional beliefs.

Discussion

Alcohol misuse is a common finding in many US veterans, as well as in the general population.^1,3 As a result, it is not uncommon to see patients with physical and psychological symptoms related to this abuse. Many of these patients will become verbally and physically abusive, thus having appropriate pharmacologic and nonpharmacologic interventions is important.

In this case study, the veteran was diagnosed with WKS and exhibited physical, cognitive, and emotional symptoms consistent with this disease. Although the physical symptoms improved with thiamine and abstinence from alcohol, their cognitive impairment, verbal outbursts, and aggressive demeanor persisted.

After using antipsychotic and anxiolytic medications with minimal clinical improvement, a trial of acetaminophen 650 mg 3 times daily was instituted. The patient’s behavior improved; demeanor became calmer, and they were easily redirected by the nursing staff. Psychological support was again employed, which enhanced and supported the veteran’s calmer demeanor. Although there is limited medical literature on the use of acetaminophen in clinical situations not related to pain, there has been research documenting its effect on social interaction.^9,10

Acetaminophen is an analgesic medication that acts through central neural mechanisms. It has been hypothesized that social and physical pain rely on shared neurochemical underpinnings, and some of the regions of the brain involved in affective experience of physical pain also have been found to be involved in the experience of social pain.¹¹ Acetaminophen may impact an individual’s social well-being as social pain processes.¹¹ It has been shown to blunt reactivity to both physical pain as well as negative stimuli.¹¹

Conclusions

A 2019 survey on alcohol and drug use found 5.6% of adults aged ≥ 18 have an alcohol use disorder.¹² In severe cases, this can result in WKS. Although replacement of thiamine is critical for physical improvement, psychological deficits may persist. Small studies have advanced the concept of using scheduled acetaminophen even when the patient is not verbalizing or displaying pain.¹³ Although more research needs to be done on this topic, this palliative approach may be worth considering, especially if the risks of antipsychotics and anxiolytics outweigh the benefits.

If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.

According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, AD is associated with difficulty falling asleep, nighttime awakenings, early morning awakenings, increased daytime sleepiness, decreased sleep efficiency, increased arousals, awakenings, and sleep fragmentation, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.

During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:

When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.

How long does it take for you to fall asleep?

Do you wake up in the middle of the night, and for how long? What do you do if you wake up?

When do you wake up in the morning? Is it on your own, or with an alarm clock?

Does this schedule change on nonworkdays?

Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?

Do you snore? Meaning, is there concern for sleep apnea?

Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.

The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”

Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.

Dr. Abbott reported having no financial disclosures.

dbrunk@mdedge.com

If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.

According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, AD is associated with difficulty falling asleep, nighttime awakenings, early morning awakenings, increased daytime sleepiness, decreased sleep efficiency, increased arousals, awakenings, and sleep fragmentation, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.

During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:

When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.

How long does it take for you to fall asleep?

Do you wake up in the middle of the night, and for how long? What do you do if you wake up?

When do you wake up in the morning? Is it on your own, or with an alarm clock?

Does this schedule change on nonworkdays?

Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?

Do you snore? Meaning, is there concern for sleep apnea?

Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.

The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”

Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.

Dr. Abbott reported having no financial disclosures.

dbrunk@mdedge.com

If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.

According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, AD is associated with difficulty falling asleep, nighttime awakenings, early morning awakenings, increased daytime sleepiness, decreased sleep efficiency, increased arousals, awakenings, and sleep fragmentation, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.

During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:

When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.

How long does it take for you to fall asleep?

Do you wake up in the middle of the night, and for how long? What do you do if you wake up?

When do you wake up in the morning? Is it on your own, or with an alarm clock?

Does this schedule change on nonworkdays?

Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?

Do you snore? Meaning, is there concern for sleep apnea?

Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.

The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”

Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.

Dr. Abbott reported having no financial disclosures.

dbrunk@mdedge.com

A specialty group is asking federal and state governments to preserve and expand access to telehealth services for children with developmental and behavioral problems.

Citing the success during the COVID-19 pandemic of telehealth for these patients, the Society for Developmental and Behavioral Pediatrics (SDBP) has issued a position statement in its official journal calling for continued use of video and telephone for home-based diagnostic assessments, medication management follow-ups, and therapeutic interventions for children  with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other neurodevelopmental conditions.

“Telehealth offers plenty of opportunities for quick check-ins. It can offer some crisis management opportunities ... to address a parent’s concern about challenging behaviors or navigating school system issues or developmental needs,” lead author Robert D. Keder, MD, assistant professor of pediatrics at University of Connecticut, Farmington, and cochair of SDBP’s Advocacy Committee, told this news organization.

“The video visit does really offer us so much more. It’s so enriching and lets us as providers meet the child in their natural home environment. The real magic of a video visit is we haven’t done house calls as a medical society for decades. But now, literally, the power of telehealth lets us do a house call.”

In the face of the pandemic, emergency government policies allowed care to continue remotely via telehealth, including video and phone calls. The policies have allowed patients to have video visits in their own home, lifted provider licensure requirements for visits across state lines, and allowed reimbursement not only for video visits but also for telephone encounters.

As a result, the field of developmental and behavioral pediatrics (DBP) has recognized telehealth as a viable and useful model of care for children with neurodevelopmental disorders, said Neelkamal Soares, MD, a member of the society’s board and a coauthor of the position paper.

“Telehealth has been helpful in mitigating barriers families often face when attending in-person visits,” such as the lack of transportation and child care, missed work hours, and other issues, said Dr. Soares, professor of pediatric and adolescent medicine at Western Michigan University Stryker in Kalamazoo. At the same time, the growth in the use of the technology has highlighted additional obstacles to equitable access to care, including broadband connectivity, digital literacy, and the availability of interpretation and sign language services, he said.

Dr. Keder said telehealth has enabled him to better help with behavior management by observing children where they are most comfortable. Remote visits also allow him to consider information such as furniture arrangements and how that can affect the patient’s living conditions, and also sibling interactions, learning and homework, eating, and sleep.

Telemedicine conferences enable DBP specialists to facilitate care collaboration with different members of the patient’s care team. Consent from a family and a click of a button allows for therapists, early intervention specialists, teachers, school nurses, or even primary care providers the capacity to participate in a telehealth visit, he said.

Dr. Keder said the future of telehealth is uncertain. The policies from the pandemic may expire in the near term and vary from state to state. The goal of the policy statement is to advocate for legislation and policies that support ongoing, equitable, home-based telehealth care for patients seen by DBP providers while ensuring equitable access to DBP in general.

Kate Benton, PhD, a clinical psychologist with Lurie Children’s Hospital at Northwestern Medicine Central DuPage Hospital in Winfield, Ill., said the society has done an excellent job of explaining the need to maintain telehealth in light of the shortage of pediatricians, clinical psychologists, and other professionals in the field.

“Telehealth has opened new avenues for these patients who otherwise have difficulty seeing specialists. This is a population of children who without telehealth have significant challenges in getting access to care,” she said.

Wendy Fournier, mother of an autistic child and president of the National Autism Association, said telehealth can be beneficial for some individuals with the disorder.

“There are many aspects of in-person doctor visits that can be overwhelming, including bright lights, many people talking, waiting for the doctor, being comfortable with the doctor’s touch, etc.,” Ms. Fournier said in an interview. “All of these things can cause sensory and emotional dysregulation leading to overwhelming anxiety and fear.”

Visits to the doctor can be especially difficult for people who are nonverbal and unable to express their discomfort, said. 

“At my daughter’s last medical appointment, she could not stay in the exam room and pulled me out the door. Thankfully, we have an understanding and compassionate physician who finished our appointment in our car. I believe that telehealth visits should remain available as a necessary and vital accommodation for people with disabilities,” Ms. Fournier said.
 

False equivalence?

Dr. Soares said researchers have attempted to assess the evidence of telehealth benefits in such situations as ADHD, cognitive behavioral therapy, and parent training. 

“There is a paucity of published studies that specifically look at different conditions and compare in-person to telehealth visits, but these are ongoing in autism diagnostics and other areas by several SDBP members,” he said. “Stay tuned.”

Dr. Keder added that telehealth will never replace in-person visits, but the availability of this new option gives developmental pediatricians flexibility in strategies in treating and evaluating patients.

“Both are helpful and viable models. In the pandemic, we were forced out of necessity to embrace telehealth,” he said. “Because of this, we are seeing the power and benefits telehealth offers. Now many families like a mixture of alternating in person with telehealth visits.”

The policy statement cites research that finds patients are highly satisfied with telehealth and that telehealth may cost less than in-office visits.

The report stresses that equitable access to devices needed for telehealth visits is a concern because there is disproportionate access to required technology, especially in rural and underserved communities. The Federal Communications Commission has provided grants to eligible families to offset the cost, in part, for a laptop, desktop computer, or tablet. However, more is still needed, the group said.

The position paper calls for:

• Equitable access to the infrastructure and technology for telehealth, including greater access to broadband services in rural and underserved areas.
• Increased access to devices needed to connect children with neurodevelopmental disorders with critical health care services.
• Reimbursement of interpretation services for the people who are deaf and/or have limited English proficiency.
• Mitigation of geographic barriers to accessing DBP care.
• Permitting patients to access telehealth from their home or whichever physical location provides opportunities for safe and timely care, especially for established patients.
• Ensuring more engagement by state medical licensing boards to join the Interstate Medical Licensing Compact to provide care by telehealth when there is already an insufficient geographic distribution of that type of provider in a state, as is being conducted in the field of psychology.
• Ensuring ongoing reimbursement.
• Parity in reimbursement for telehealth in-person visits.
• Increased funding for research looking into outcomes, quality, and effectiveness of telehealth services at the federal and state levels.

“Our organization can work with families to educate lawmakers, insurance administrators, and organizational leaders about the value that telehealth holds in the care of their child and family,” Dr. Soares said. “We can also conduct research to add to the evidence based around the topic to further the science around telehealth outcomes and equivalency to in-person settings.”

“With the current workforce shortage in DBP and behavioral health it is more critical than ever to maintain access to care,” Dr. Keder added. “The pandemic has provided an opportunity to better harness the amazing power of telehealth to allow for access to equitable care for families. We hope that this statement moves legislators, leaders, and voters to continue to advocate for ongoing telehealth at both the state, federal, and organizational levels.”

Dr. Benton, Dr. Keder, and Dr. Soares have disclosed no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

A specialty group is asking federal and state governments to preserve and expand access to telehealth services for children with developmental and behavioral problems.

Citing the success during the COVID-19 pandemic of telehealth for these patients, the Society for Developmental and Behavioral Pediatrics (SDBP) has issued a position statement in its official journal calling for continued use of video and telephone for home-based diagnostic assessments, medication management follow-ups, and therapeutic interventions for children  with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other neurodevelopmental conditions.

“Telehealth offers plenty of opportunities for quick check-ins. It can offer some crisis management opportunities ... to address a parent’s concern about challenging behaviors or navigating school system issues or developmental needs,” lead author Robert D. Keder, MD, assistant professor of pediatrics at University of Connecticut, Farmington, and cochair of SDBP’s Advocacy Committee, told this news organization.

“The video visit does really offer us so much more. It’s so enriching and lets us as providers meet the child in their natural home environment. The real magic of a video visit is we haven’t done house calls as a medical society for decades. But now, literally, the power of telehealth lets us do a house call.”

In the face of the pandemic, emergency government policies allowed care to continue remotely via telehealth, including video and phone calls. The policies have allowed patients to have video visits in their own home, lifted provider licensure requirements for visits across state lines, and allowed reimbursement not only for video visits but also for telephone encounters.

As a result, the field of developmental and behavioral pediatrics (DBP) has recognized telehealth as a viable and useful model of care for children with neurodevelopmental disorders, said Neelkamal Soares, MD, a member of the society’s board and a coauthor of the position paper.

“Telehealth has been helpful in mitigating barriers families often face when attending in-person visits,” such as the lack of transportation and child care, missed work hours, and other issues, said Dr. Soares, professor of pediatric and adolescent medicine at Western Michigan University Stryker in Kalamazoo. At the same time, the growth in the use of the technology has highlighted additional obstacles to equitable access to care, including broadband connectivity, digital literacy, and the availability of interpretation and sign language services, he said.

Dr. Keder said telehealth has enabled him to better help with behavior management by observing children where they are most comfortable. Remote visits also allow him to consider information such as furniture arrangements and how that can affect the patient’s living conditions, and also sibling interactions, learning and homework, eating, and sleep.

Telemedicine conferences enable DBP specialists to facilitate care collaboration with different members of the patient’s care team. Consent from a family and a click of a button allows for therapists, early intervention specialists, teachers, school nurses, or even primary care providers the capacity to participate in a telehealth visit, he said.

Dr. Keder said the future of telehealth is uncertain. The policies from the pandemic may expire in the near term and vary from state to state. The goal of the policy statement is to advocate for legislation and policies that support ongoing, equitable, home-based telehealth care for patients seen by DBP providers while ensuring equitable access to DBP in general.

Kate Benton, PhD, a clinical psychologist with Lurie Children’s Hospital at Northwestern Medicine Central DuPage Hospital in Winfield, Ill., said the society has done an excellent job of explaining the need to maintain telehealth in light of the shortage of pediatricians, clinical psychologists, and other professionals in the field.

“Telehealth has opened new avenues for these patients who otherwise have difficulty seeing specialists. This is a population of children who without telehealth have significant challenges in getting access to care,” she said.

Wendy Fournier, mother of an autistic child and president of the National Autism Association, said telehealth can be beneficial for some individuals with the disorder.

“There are many aspects of in-person doctor visits that can be overwhelming, including bright lights, many people talking, waiting for the doctor, being comfortable with the doctor’s touch, etc.,” Ms. Fournier said in an interview. “All of these things can cause sensory and emotional dysregulation leading to overwhelming anxiety and fear.”

Visits to the doctor can be especially difficult for people who are nonverbal and unable to express their discomfort, said. 

“At my daughter’s last medical appointment, she could not stay in the exam room and pulled me out the door. Thankfully, we have an understanding and compassionate physician who finished our appointment in our car. I believe that telehealth visits should remain available as a necessary and vital accommodation for people with disabilities,” Ms. Fournier said.
 

False equivalence?

Dr. Soares said researchers have attempted to assess the evidence of telehealth benefits in such situations as ADHD, cognitive behavioral therapy, and parent training. 

“There is a paucity of published studies that specifically look at different conditions and compare in-person to telehealth visits, but these are ongoing in autism diagnostics and other areas by several SDBP members,” he said. “Stay tuned.”

Dr. Keder added that telehealth will never replace in-person visits, but the availability of this new option gives developmental pediatricians flexibility in strategies in treating and evaluating patients.

“Both are helpful and viable models. In the pandemic, we were forced out of necessity to embrace telehealth,” he said. “Because of this, we are seeing the power and benefits telehealth offers. Now many families like a mixture of alternating in person with telehealth visits.”

The policy statement cites research that finds patients are highly satisfied with telehealth and that telehealth may cost less than in-office visits.

The report stresses that equitable access to devices needed for telehealth visits is a concern because there is disproportionate access to required technology, especially in rural and underserved communities. The Federal Communications Commission has provided grants to eligible families to offset the cost, in part, for a laptop, desktop computer, or tablet. However, more is still needed, the group said.

The position paper calls for:

• Equitable access to the infrastructure and technology for telehealth, including greater access to broadband services in rural and underserved areas.
• Increased access to devices needed to connect children with neurodevelopmental disorders with critical health care services.
• Reimbursement of interpretation services for the people who are deaf and/or have limited English proficiency.
• Mitigation of geographic barriers to accessing DBP care.
• Permitting patients to access telehealth from their home or whichever physical location provides opportunities for safe and timely care, especially for established patients.
• Ensuring more engagement by state medical licensing boards to join the Interstate Medical Licensing Compact to provide care by telehealth when there is already an insufficient geographic distribution of that type of provider in a state, as is being conducted in the field of psychology.
• Ensuring ongoing reimbursement.
• Parity in reimbursement for telehealth in-person visits.
• Increased funding for research looking into outcomes, quality, and effectiveness of telehealth services at the federal and state levels.

“Our organization can work with families to educate lawmakers, insurance administrators, and organizational leaders about the value that telehealth holds in the care of their child and family,” Dr. Soares said. “We can also conduct research to add to the evidence based around the topic to further the science around telehealth outcomes and equivalency to in-person settings.”

“With the current workforce shortage in DBP and behavioral health it is more critical than ever to maintain access to care,” Dr. Keder added. “The pandemic has provided an opportunity to better harness the amazing power of telehealth to allow for access to equitable care for families. We hope that this statement moves legislators, leaders, and voters to continue to advocate for ongoing telehealth at both the state, federal, and organizational levels.”

Dr. Benton, Dr. Keder, and Dr. Soares have disclosed no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

A specialty group is asking federal and state governments to preserve and expand access to telehealth services for children with developmental and behavioral problems.

Citing the success during the COVID-19 pandemic of telehealth for these patients, the Society for Developmental and Behavioral Pediatrics (SDBP) has issued a position statement in its official journal calling for continued use of video and telephone for home-based diagnostic assessments, medication management follow-ups, and therapeutic interventions for children  with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other neurodevelopmental conditions.

“Telehealth offers plenty of opportunities for quick check-ins. It can offer some crisis management opportunities ... to address a parent’s concern about challenging behaviors or navigating school system issues or developmental needs,” lead author Robert D. Keder, MD, assistant professor of pediatrics at University of Connecticut, Farmington, and cochair of SDBP’s Advocacy Committee, told this news organization.

“The video visit does really offer us so much more. It’s so enriching and lets us as providers meet the child in their natural home environment. The real magic of a video visit is we haven’t done house calls as a medical society for decades. But now, literally, the power of telehealth lets us do a house call.”

In the face of the pandemic, emergency government policies allowed care to continue remotely via telehealth, including video and phone calls. The policies have allowed patients to have video visits in their own home, lifted provider licensure requirements for visits across state lines, and allowed reimbursement not only for video visits but also for telephone encounters.

As a result, the field of developmental and behavioral pediatrics (DBP) has recognized telehealth as a viable and useful model of care for children with neurodevelopmental disorders, said Neelkamal Soares, MD, a member of the society’s board and a coauthor of the position paper.

“Telehealth has been helpful in mitigating barriers families often face when attending in-person visits,” such as the lack of transportation and child care, missed work hours, and other issues, said Dr. Soares, professor of pediatric and adolescent medicine at Western Michigan University Stryker in Kalamazoo. At the same time, the growth in the use of the technology has highlighted additional obstacles to equitable access to care, including broadband connectivity, digital literacy, and the availability of interpretation and sign language services, he said.

Dr. Keder said telehealth has enabled him to better help with behavior management by observing children where they are most comfortable. Remote visits also allow him to consider information such as furniture arrangements and how that can affect the patient’s living conditions, and also sibling interactions, learning and homework, eating, and sleep.

Telemedicine conferences enable DBP specialists to facilitate care collaboration with different members of the patient’s care team. Consent from a family and a click of a button allows for therapists, early intervention specialists, teachers, school nurses, or even primary care providers the capacity to participate in a telehealth visit, he said.

Dr. Keder said the future of telehealth is uncertain. The policies from the pandemic may expire in the near term and vary from state to state. The goal of the policy statement is to advocate for legislation and policies that support ongoing, equitable, home-based telehealth care for patients seen by DBP providers while ensuring equitable access to DBP in general.

Kate Benton, PhD, a clinical psychologist with Lurie Children’s Hospital at Northwestern Medicine Central DuPage Hospital in Winfield, Ill., said the society has done an excellent job of explaining the need to maintain telehealth in light of the shortage of pediatricians, clinical psychologists, and other professionals in the field.

“Telehealth has opened new avenues for these patients who otherwise have difficulty seeing specialists. This is a population of children who without telehealth have significant challenges in getting access to care,” she said.

Wendy Fournier, mother of an autistic child and president of the National Autism Association, said telehealth can be beneficial for some individuals with the disorder.

“There are many aspects of in-person doctor visits that can be overwhelming, including bright lights, many people talking, waiting for the doctor, being comfortable with the doctor’s touch, etc.,” Ms. Fournier said in an interview. “All of these things can cause sensory and emotional dysregulation leading to overwhelming anxiety and fear.”

Visits to the doctor can be especially difficult for people who are nonverbal and unable to express their discomfort, said. 

“At my daughter’s last medical appointment, she could not stay in the exam room and pulled me out the door. Thankfully, we have an understanding and compassionate physician who finished our appointment in our car. I believe that telehealth visits should remain available as a necessary and vital accommodation for people with disabilities,” Ms. Fournier said.
 

False equivalence?

Dr. Soares said researchers have attempted to assess the evidence of telehealth benefits in such situations as ADHD, cognitive behavioral therapy, and parent training. 

“There is a paucity of published studies that specifically look at different conditions and compare in-person to telehealth visits, but these are ongoing in autism diagnostics and other areas by several SDBP members,” he said. “Stay tuned.”

Dr. Keder added that telehealth will never replace in-person visits, but the availability of this new option gives developmental pediatricians flexibility in strategies in treating and evaluating patients.

“Both are helpful and viable models. In the pandemic, we were forced out of necessity to embrace telehealth,” he said. “Because of this, we are seeing the power and benefits telehealth offers. Now many families like a mixture of alternating in person with telehealth visits.”

The policy statement cites research that finds patients are highly satisfied with telehealth and that telehealth may cost less than in-office visits.

The report stresses that equitable access to devices needed for telehealth visits is a concern because there is disproportionate access to required technology, especially in rural and underserved communities. The Federal Communications Commission has provided grants to eligible families to offset the cost, in part, for a laptop, desktop computer, or tablet. However, more is still needed, the group said.

The position paper calls for:

• Equitable access to the infrastructure and technology for telehealth, including greater access to broadband services in rural and underserved areas.
• Increased access to devices needed to connect children with neurodevelopmental disorders with critical health care services.
• Reimbursement of interpretation services for the people who are deaf and/or have limited English proficiency.
• Mitigation of geographic barriers to accessing DBP care.
• Permitting patients to access telehealth from their home or whichever physical location provides opportunities for safe and timely care, especially for established patients.
• Ensuring more engagement by state medical licensing boards to join the Interstate Medical Licensing Compact to provide care by telehealth when there is already an insufficient geographic distribution of that type of provider in a state, as is being conducted in the field of psychology.
• Ensuring ongoing reimbursement.
• Parity in reimbursement for telehealth in-person visits.
• Increased funding for research looking into outcomes, quality, and effectiveness of telehealth services at the federal and state levels.

“Our organization can work with families to educate lawmakers, insurance administrators, and organizational leaders about the value that telehealth holds in the care of their child and family,” Dr. Soares said. “We can also conduct research to add to the evidence based around the topic to further the science around telehealth outcomes and equivalency to in-person settings.”

“With the current workforce shortage in DBP and behavioral health it is more critical than ever to maintain access to care,” Dr. Keder added. “The pandemic has provided an opportunity to better harness the amazing power of telehealth to allow for access to equitable care for families. We hope that this statement moves legislators, leaders, and voters to continue to advocate for ongoing telehealth at both the state, federal, and organizational levels.”

Dr. Benton, Dr. Keder, and Dr. Soares have disclosed no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mutations in genes associated with cardiac and seizure disorders appear to be linked to sudden unexplained deaths in young children and may explain nearly 9% of such cases, researchers have found.

Previous studies have found de novo genetic variants – those not found in either parent but which occur for the first time in their offspring – that increase the risk of cardiac and seizure disorders, but research on sudden unexplained deaths in children (SUDC) is limited, according to Matthew Halvorsen, PhD, of the University of North Carolina at Chapel Hill, and colleagues. Most cases of SUDC occur in children aged 1-4 years, and a lack of standardized investigation systems likely leads to misclassification of these deaths, they said.

Compared with sudden infant death syndrome (SIDS), which occurs in approximately 1,400 children in the United States each year, approximately 400 children aged 1 year and older die from SUDC annually. A major obstacle to studying these cases is that so-called molecular autopsies – which incorporate genetic analysis into the postmortem examination – typically do not assess the parents’ genetic information and thus limit the ability to identify de novo mutations, they added.

In a study published in the Proceedings of the National Academy of Sciences, Dr. Halvorsen’s group obtained whole exome sequence data from 124 “trios,” meaning a dead child and two living parents. They tested for excessive de novo mutations for different genes involved in conditions that included cardiac arrhythmias and epilepsy. The average age at the time of death for the children was 34.2 months; 54% were male, and 82% were White.

Children who died of SUDC were nearly 10 times as likely to have de novo mutations in genes associated with cardiac and seizure disorders as were unrelated healthy controls (odds ratio, 9.76). Most pathogenic variants were de novo, which highlights the importance of trio studies, the researchers noted.

The researchers identified 11 variants associated with increased risk of SUDC, 7 of which were de novo. Three of the 124 cases carried mutations (two for RYR2 and 1 for TNNI3) affecting genes in the CardiacEpilepsy dataset proposed by the American College of Medical Genetics and Genomics, strengthening the connection to seizure disorders.

Another notable finding was the identification of six de novo mutations involved in altering calcium-related regulation, which suggests a cardiac susceptibility to sudden death.

The data support “novel genetic causes of pediatric sudden deaths that could be discovered with larger cohorts,” the researchers noted. Taken together, they say, the gene mutations could play a role in approximately 9% of SUDC cases.

The study findings were limited by several factors, including lack of population-based case ascertainment, exclusive focus on unexplained deaths, potentially missed mutations, and use of DNA from blood as opposed to organs, the researchers noted.

However, they concluded, “the data indicate that deleterious de novo mutations are significant genetic risk factors for childhood sudden unexplained death, and that their identification may lead to medical intervention that ultimately saves lives.”

Findings highlight impact of SUDC

“This study is important because SUDC is a much more pressing medical need than most people realize,” said Richard Tsien, PhD, of New York University Langone Medical Center, and the corresponding author of the study.

Although SUDC is less common than SIDS, SUDC has essentially no targeted research funding, Dr. Tsien said. Study coauthor Laura Gould, MA, a researcher and mother who lost a young child to SUDC, worked with Orrin Devinsky, MD, to create a registry for families with cases of SUDC. This registry was instrumental in allowing the researchers to “do the molecular detective work we need to do” to see whether a genetic basis exists for SUDC, Dr. Tsien said.

“The detective work comes up with a consistent story,” he said. “More than half of the genes that we found are involved in the normal function of the heart and brain,” performing such functions as delivering calcium ions to the inside of the heart cells and nerve cells.

The study “is the first of its kind,” given the difficulty of acquiring DNA from the child and two parents in SUDC cases, Dr. Tsien said.

Overall, approximately 10% of the cases have a compelling explanation based on the coding of DNA, Dr. Tsien said. From a clinical standpoint, that information might affect what a clinician says to a parent.

A key takeaway is that most of the genetic mutations are spontaneous and are not inherited from the parents, Dr. Tsien said. The study findings indicate that parents who suffer an SUDC loss need not be discouraged from having children, he added.

For the long term, “the more we understand about these disorders, the more information we can offer to families,” he said. Eventually, clinicians might be able to use genetics to identify signs of when SUDC might be more likely. “For example, if a child shows a very mild seizure, this would alert them that there might be potential for a more drastic outcome.”

Meanwhile, families with SUDC cases may find support and benefit in signing up for the registry and knowing that other families have been through a similar experience, Dr. Tsien said.

Genetic studies create opportunities

A significant portion of pediatric mortality remains unexplained, according to Richard D. Goldstein, MD, of Boston Children’s Hospital. One reason is the lack of a formal diagnostic code to identify these deaths.

Research to date has suggested links between SUDC and a family history of febrile seizures, as well as differences in brain structure associated with epilepsy, Dr. Goldstein said.

“An important hypothesis is that these deaths are part of a continuum that also includes stillbirths, SIDS, and sudden unexpected death in epilepsy [SUDEP],” Dr. Goldstein said. “By mandate, investigations of these deaths occur under the jurisdiction of medical examiners and coroners and have, for the most part, been insulated from developments in modern medicine like genomics and proteomics, elements of what are referred to as the molecular autopsy, and studies such as the current study bring attention to what is being missed.”

Dr. Goldstein said the new study buttresses the “conventional clinical suspicion” about the likely causes of SUDC, “but also strengthens the association between sudden unexpected death in pediatrics (SUDP) and SUDEP that we and others have been positing. I think the researchers very nicely make the point that epilepsy and cardiac arrhythmia genes are not as separated in their effects as many would believe.”

As for the clinical applicability of the findings, Dr. Goldstein said medicine needs to offer parents more: “Pediatric deaths without explanation deserve more than a forensic investigation that concerns itself mostly with whether there has been foul play,” he said. “We need to figure out how to engage families, at an incredibly vulnerable time, in helping find the cause of the child’s death and also contributing to needed research. Most of the reported variants were de novo, which means that parent participation is needed to figure out these genetic factors but also that we can offer reassurance to families that other children are not at risk.”

The study was supported by the SUDC Foundation and Finding a Cure for Epilepsy and Seizures (New York University). Dr. Tsien disclosed support from the National Institutes of Health and a grant from FACES. Dr. Goldstein reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mutations in genes associated with cardiac and seizure disorders appear to be linked to sudden unexplained deaths in young children and may explain nearly 9% of such cases, researchers have found.

Previous studies have found de novo genetic variants – those not found in either parent but which occur for the first time in their offspring – that increase the risk of cardiac and seizure disorders, but research on sudden unexplained deaths in children (SUDC) is limited, according to Matthew Halvorsen, PhD, of the University of North Carolina at Chapel Hill, and colleagues. Most cases of SUDC occur in children aged 1-4 years, and a lack of standardized investigation systems likely leads to misclassification of these deaths, they said.

Compared with sudden infant death syndrome (SIDS), which occurs in approximately 1,400 children in the United States each year, approximately 400 children aged 1 year and older die from SUDC annually. A major obstacle to studying these cases is that so-called molecular autopsies – which incorporate genetic analysis into the postmortem examination – typically do not assess the parents’ genetic information and thus limit the ability to identify de novo mutations, they added.

In a study published in the Proceedings of the National Academy of Sciences, Dr. Halvorsen’s group obtained whole exome sequence data from 124 “trios,” meaning a dead child and two living parents. They tested for excessive de novo mutations for different genes involved in conditions that included cardiac arrhythmias and epilepsy. The average age at the time of death for the children was 34.2 months; 54% were male, and 82% were White.

Children who died of SUDC were nearly 10 times as likely to have de novo mutations in genes associated with cardiac and seizure disorders as were unrelated healthy controls (odds ratio, 9.76). Most pathogenic variants were de novo, which highlights the importance of trio studies, the researchers noted.

The researchers identified 11 variants associated with increased risk of SUDC, 7 of which were de novo. Three of the 124 cases carried mutations (two for RYR2 and 1 for TNNI3) affecting genes in the CardiacEpilepsy dataset proposed by the American College of Medical Genetics and Genomics, strengthening the connection to seizure disorders.

Another notable finding was the identification of six de novo mutations involved in altering calcium-related regulation, which suggests a cardiac susceptibility to sudden death.

The data support “novel genetic causes of pediatric sudden deaths that could be discovered with larger cohorts,” the researchers noted. Taken together, they say, the gene mutations could play a role in approximately 9% of SUDC cases.

The study findings were limited by several factors, including lack of population-based case ascertainment, exclusive focus on unexplained deaths, potentially missed mutations, and use of DNA from blood as opposed to organs, the researchers noted.

However, they concluded, “the data indicate that deleterious de novo mutations are significant genetic risk factors for childhood sudden unexplained death, and that their identification may lead to medical intervention that ultimately saves lives.”

Findings highlight impact of SUDC

“This study is important because SUDC is a much more pressing medical need than most people realize,” said Richard Tsien, PhD, of New York University Langone Medical Center, and the corresponding author of the study.

Although SUDC is less common than SIDS, SUDC has essentially no targeted research funding, Dr. Tsien said. Study coauthor Laura Gould, MA, a researcher and mother who lost a young child to SUDC, worked with Orrin Devinsky, MD, to create a registry for families with cases of SUDC. This registry was instrumental in allowing the researchers to “do the molecular detective work we need to do” to see whether a genetic basis exists for SUDC, Dr. Tsien said.

“The detective work comes up with a consistent story,” he said. “More than half of the genes that we found are involved in the normal function of the heart and brain,” performing such functions as delivering calcium ions to the inside of the heart cells and nerve cells.

The study “is the first of its kind,” given the difficulty of acquiring DNA from the child and two parents in SUDC cases, Dr. Tsien said.

Overall, approximately 10% of the cases have a compelling explanation based on the coding of DNA, Dr. Tsien said. From a clinical standpoint, that information might affect what a clinician says to a parent.

A key takeaway is that most of the genetic mutations are spontaneous and are not inherited from the parents, Dr. Tsien said. The study findings indicate that parents who suffer an SUDC loss need not be discouraged from having children, he added.

For the long term, “the more we understand about these disorders, the more information we can offer to families,” he said. Eventually, clinicians might be able to use genetics to identify signs of when SUDC might be more likely. “For example, if a child shows a very mild seizure, this would alert them that there might be potential for a more drastic outcome.”

Meanwhile, families with SUDC cases may find support and benefit in signing up for the registry and knowing that other families have been through a similar experience, Dr. Tsien said.

Genetic studies create opportunities

A significant portion of pediatric mortality remains unexplained, according to Richard D. Goldstein, MD, of Boston Children’s Hospital. One reason is the lack of a formal diagnostic code to identify these deaths.

Research to date has suggested links between SUDC and a family history of febrile seizures, as well as differences in brain structure associated with epilepsy, Dr. Goldstein said.

“An important hypothesis is that these deaths are part of a continuum that also includes stillbirths, SIDS, and sudden unexpected death in epilepsy [SUDEP],” Dr. Goldstein said. “By mandate, investigations of these deaths occur under the jurisdiction of medical examiners and coroners and have, for the most part, been insulated from developments in modern medicine like genomics and proteomics, elements of what are referred to as the molecular autopsy, and studies such as the current study bring attention to what is being missed.”

Dr. Goldstein said the new study buttresses the “conventional clinical suspicion” about the likely causes of SUDC, “but also strengthens the association between sudden unexpected death in pediatrics (SUDP) and SUDEP that we and others have been positing. I think the researchers very nicely make the point that epilepsy and cardiac arrhythmia genes are not as separated in their effects as many would believe.”

As for the clinical applicability of the findings, Dr. Goldstein said medicine needs to offer parents more: “Pediatric deaths without explanation deserve more than a forensic investigation that concerns itself mostly with whether there has been foul play,” he said. “We need to figure out how to engage families, at an incredibly vulnerable time, in helping find the cause of the child’s death and also contributing to needed research. Most of the reported variants were de novo, which means that parent participation is needed to figure out these genetic factors but also that we can offer reassurance to families that other children are not at risk.”

The study was supported by the SUDC Foundation and Finding a Cure for Epilepsy and Seizures (New York University). Dr. Tsien disclosed support from the National Institutes of Health and a grant from FACES. Dr. Goldstein reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mutations in genes associated with cardiac and seizure disorders appear to be linked to sudden unexplained deaths in young children and may explain nearly 9% of such cases, researchers have found.

Previous studies have found de novo genetic variants – those not found in either parent but which occur for the first time in their offspring – that increase the risk of cardiac and seizure disorders, but research on sudden unexplained deaths in children (SUDC) is limited, according to Matthew Halvorsen, PhD, of the University of North Carolina at Chapel Hill, and colleagues. Most cases of SUDC occur in children aged 1-4 years, and a lack of standardized investigation systems likely leads to misclassification of these deaths, they said.

Compared with sudden infant death syndrome (SIDS), which occurs in approximately 1,400 children in the United States each year, approximately 400 children aged 1 year and older die from SUDC annually. A major obstacle to studying these cases is that so-called molecular autopsies – which incorporate genetic analysis into the postmortem examination – typically do not assess the parents’ genetic information and thus limit the ability to identify de novo mutations, they added.

In a study published in the Proceedings of the National Academy of Sciences, Dr. Halvorsen’s group obtained whole exome sequence data from 124 “trios,” meaning a dead child and two living parents. They tested for excessive de novo mutations for different genes involved in conditions that included cardiac arrhythmias and epilepsy. The average age at the time of death for the children was 34.2 months; 54% were male, and 82% were White.

Children who died of SUDC were nearly 10 times as likely to have de novo mutations in genes associated with cardiac and seizure disorders as were unrelated healthy controls (odds ratio, 9.76). Most pathogenic variants were de novo, which highlights the importance of trio studies, the researchers noted.

The researchers identified 11 variants associated with increased risk of SUDC, 7 of which were de novo. Three of the 124 cases carried mutations (two for RYR2 and 1 for TNNI3) affecting genes in the CardiacEpilepsy dataset proposed by the American College of Medical Genetics and Genomics, strengthening the connection to seizure disorders.

Another notable finding was the identification of six de novo mutations involved in altering calcium-related regulation, which suggests a cardiac susceptibility to sudden death.

The data support “novel genetic causes of pediatric sudden deaths that could be discovered with larger cohorts,” the researchers noted. Taken together, they say, the gene mutations could play a role in approximately 9% of SUDC cases.

The study findings were limited by several factors, including lack of population-based case ascertainment, exclusive focus on unexplained deaths, potentially missed mutations, and use of DNA from blood as opposed to organs, the researchers noted.

However, they concluded, “the data indicate that deleterious de novo mutations are significant genetic risk factors for childhood sudden unexplained death, and that their identification may lead to medical intervention that ultimately saves lives.”

Findings highlight impact of SUDC

“This study is important because SUDC is a much more pressing medical need than most people realize,” said Richard Tsien, PhD, of New York University Langone Medical Center, and the corresponding author of the study.

Although SUDC is less common than SIDS, SUDC has essentially no targeted research funding, Dr. Tsien said. Study coauthor Laura Gould, MA, a researcher and mother who lost a young child to SUDC, worked with Orrin Devinsky, MD, to create a registry for families with cases of SUDC. This registry was instrumental in allowing the researchers to “do the molecular detective work we need to do” to see whether a genetic basis exists for SUDC, Dr. Tsien said.

“The detective work comes up with a consistent story,” he said. “More than half of the genes that we found are involved in the normal function of the heart and brain,” performing such functions as delivering calcium ions to the inside of the heart cells and nerve cells.

The study “is the first of its kind,” given the difficulty of acquiring DNA from the child and two parents in SUDC cases, Dr. Tsien said.

Overall, approximately 10% of the cases have a compelling explanation based on the coding of DNA, Dr. Tsien said. From a clinical standpoint, that information might affect what a clinician says to a parent.

A key takeaway is that most of the genetic mutations are spontaneous and are not inherited from the parents, Dr. Tsien said. The study findings indicate that parents who suffer an SUDC loss need not be discouraged from having children, he added.

For the long term, “the more we understand about these disorders, the more information we can offer to families,” he said. Eventually, clinicians might be able to use genetics to identify signs of when SUDC might be more likely. “For example, if a child shows a very mild seizure, this would alert them that there might be potential for a more drastic outcome.”

Meanwhile, families with SUDC cases may find support and benefit in signing up for the registry and knowing that other families have been through a similar experience, Dr. Tsien said.

Genetic studies create opportunities

A significant portion of pediatric mortality remains unexplained, according to Richard D. Goldstein, MD, of Boston Children’s Hospital. One reason is the lack of a formal diagnostic code to identify these deaths.

Research to date has suggested links between SUDC and a family history of febrile seizures, as well as differences in brain structure associated with epilepsy, Dr. Goldstein said.

“An important hypothesis is that these deaths are part of a continuum that also includes stillbirths, SIDS, and sudden unexpected death in epilepsy [SUDEP],” Dr. Goldstein said. “By mandate, investigations of these deaths occur under the jurisdiction of medical examiners and coroners and have, for the most part, been insulated from developments in modern medicine like genomics and proteomics, elements of what are referred to as the molecular autopsy, and studies such as the current study bring attention to what is being missed.”

Dr. Goldstein said the new study buttresses the “conventional clinical suspicion” about the likely causes of SUDC, “but also strengthens the association between sudden unexpected death in pediatrics (SUDP) and SUDEP that we and others have been positing. I think the researchers very nicely make the point that epilepsy and cardiac arrhythmia genes are not as separated in their effects as many would believe.”

As for the clinical applicability of the findings, Dr. Goldstein said medicine needs to offer parents more: “Pediatric deaths without explanation deserve more than a forensic investigation that concerns itself mostly with whether there has been foul play,” he said. “We need to figure out how to engage families, at an incredibly vulnerable time, in helping find the cause of the child’s death and also contributing to needed research. Most of the reported variants were de novo, which means that parent participation is needed to figure out these genetic factors but also that we can offer reassurance to families that other children are not at risk.”

The study was supported by the SUDC Foundation and Finding a Cure for Epilepsy and Seizures (New York University). Dr. Tsien disclosed support from the National Institutes of Health and a grant from FACES. Dr. Goldstein reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Updated guidelines from the American Academy of Neurology advise against prescribing opioids for painful diabetic neuropathy – but note that several other oral and topical therapies may help ease pain.

Painful diabetic neuropathy is very common and can greatly affect an individual’s quality of life, guideline author Brian Callaghan, MD, University of Michigan, Ann Arbor, noted in a news release.

“This guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” Dr. Callaghan said.

The recommendations update the 2011 AAN guideline on the treatment of painful diabetic neuropathy. The new guidance was published online Dec. 27, 2021, in Neurology and has been endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine.
 

Multiple options

To update the guideline, an expert panel reviewed data from more than 100 randomized controlled trials published from January 2008 to April 2020.

The panel noted that more than 16% of individuals with diabetes experience painful diabetic neuropathy, but it often goes unrecognized and untreated. The guideline recommends clinicians assess patients with diabetes for peripheral neuropathic pain and its effect on their function and quality of life.

Before prescribing treatment, health providers should determine if the patient also has mood or sleep problems as both can influence pain perception.

The guideline recommends offering one of four classes of oral medications found to be effective for neuropathic pain: tricyclic antidepressants such as amitriptyline, nortriptyline, or imipramine; serotonin norepinephrine reuptake inhibitors such as duloxetine, venlafaxine, or desvenlafaxine; gabapentinoids such as gabapentin or pregabalin; and/or sodium channel blockers such as carbamazepine, oxcarbazepine, lamotrigine, or lacosamide.

All four classes of medications have “comparable effect sizes just above or just below our cutoff for a medium effect size” (standardized median difference, 0.5), the panel noted.

In addition, “new studies on sodium channel blockers published since the last guideline have resulted in these drugs now being recommended and considered as effective at providing pain relief as the other drug classes recommended in this guideline,” said Dr. Callaghan.

When an initial medication fails to provide meaningful improvement in pain, or produces significant side effects, a trial of another medication from a different class is recommended.
 

Pain reduction, not elimination

Opioids are not recommended for painful diabetic neuropathy. Not only do they come with risks, there is also no strong evidence they are effective for painful diabetic neuropathy in the long term, the panel wrote. Tramadol and tapentadol are also not recommended for the treatment of painful diabetic neuropathy.

“Current evidence suggests that the risks of the use of opioids for painful diabetic neuropathy therapy outweigh the benefits, so they should not be prescribed,” Dr. Callaghan said.

For patients interested in trying topical, nontraditional, or nondrug interventions to reduce pain, the guideline recommends a number of options including capsaicin, glyceryl trinitrate spray, and Citrullus colocynthis. Ginkgo biloba, exercise, mindfulness, cognitive-behavioral therapy, and tai chi are also suggested.

“It is important to note that the recommended drugs and topical treatments in this guideline may not eliminate pain, but they have been shown to reduce pain,” Dr. Callaghan said. “The good news is there are many treatment options for painful diabetic neuropathy, so a treatment plan can be tailored specifically to each person living with this condition.”

Along with the updated guideline, the AAN has also published a new Polyneuropathy Quality Measurement Set to assist neurologists and other health care providers in treating patients with painful diabetic neuropathy.

The updated guideline was developed with financial support from the AAN.

A version of this article first appeared on Medscape.com.

Updated guidelines from the American Academy of Neurology advise against prescribing opioids for painful diabetic neuropathy – but note that several other oral and topical therapies may help ease pain.

Painful diabetic neuropathy is very common and can greatly affect an individual’s quality of life, guideline author Brian Callaghan, MD, University of Michigan, Ann Arbor, noted in a news release.

“This guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” Dr. Callaghan said.

The recommendations update the 2011 AAN guideline on the treatment of painful diabetic neuropathy. The new guidance was published online Dec. 27, 2021, in Neurology and has been endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine.
 

Multiple options

To update the guideline, an expert panel reviewed data from more than 100 randomized controlled trials published from January 2008 to April 2020.

The panel noted that more than 16% of individuals with diabetes experience painful diabetic neuropathy, but it often goes unrecognized and untreated. The guideline recommends clinicians assess patients with diabetes for peripheral neuropathic pain and its effect on their function and quality of life.

Before prescribing treatment, health providers should determine if the patient also has mood or sleep problems as both can influence pain perception.

The guideline recommends offering one of four classes of oral medications found to be effective for neuropathic pain: tricyclic antidepressants such as amitriptyline, nortriptyline, or imipramine; serotonin norepinephrine reuptake inhibitors such as duloxetine, venlafaxine, or desvenlafaxine; gabapentinoids such as gabapentin or pregabalin; and/or sodium channel blockers such as carbamazepine, oxcarbazepine, lamotrigine, or lacosamide.

All four classes of medications have “comparable effect sizes just above or just below our cutoff for a medium effect size” (standardized median difference, 0.5), the panel noted.

In addition, “new studies on sodium channel blockers published since the last guideline have resulted in these drugs now being recommended and considered as effective at providing pain relief as the other drug classes recommended in this guideline,” said Dr. Callaghan.

When an initial medication fails to provide meaningful improvement in pain, or produces significant side effects, a trial of another medication from a different class is recommended.
 

Pain reduction, not elimination

Opioids are not recommended for painful diabetic neuropathy. Not only do they come with risks, there is also no strong evidence they are effective for painful diabetic neuropathy in the long term, the panel wrote. Tramadol and tapentadol are also not recommended for the treatment of painful diabetic neuropathy.

“Current evidence suggests that the risks of the use of opioids for painful diabetic neuropathy therapy outweigh the benefits, so they should not be prescribed,” Dr. Callaghan said.

For patients interested in trying topical, nontraditional, or nondrug interventions to reduce pain, the guideline recommends a number of options including capsaicin, glyceryl trinitrate spray, and Citrullus colocynthis. Ginkgo biloba, exercise, mindfulness, cognitive-behavioral therapy, and tai chi are also suggested.

“It is important to note that the recommended drugs and topical treatments in this guideline may not eliminate pain, but they have been shown to reduce pain,” Dr. Callaghan said. “The good news is there are many treatment options for painful diabetic neuropathy, so a treatment plan can be tailored specifically to each person living with this condition.”

Along with the updated guideline, the AAN has also published a new Polyneuropathy Quality Measurement Set to assist neurologists and other health care providers in treating patients with painful diabetic neuropathy.

The updated guideline was developed with financial support from the AAN.

A version of this article first appeared on Medscape.com.

Updated guidelines from the American Academy of Neurology advise against prescribing opioids for painful diabetic neuropathy – but note that several other oral and topical therapies may help ease pain.

Painful diabetic neuropathy is very common and can greatly affect an individual’s quality of life, guideline author Brian Callaghan, MD, University of Michigan, Ann Arbor, noted in a news release.

“This guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” Dr. Callaghan said.

The recommendations update the 2011 AAN guideline on the treatment of painful diabetic neuropathy. The new guidance was published online Dec. 27, 2021, in Neurology and has been endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine.
 

Multiple options

To update the guideline, an expert panel reviewed data from more than 100 randomized controlled trials published from January 2008 to April 2020.

The panel noted that more than 16% of individuals with diabetes experience painful diabetic neuropathy, but it often goes unrecognized and untreated. The guideline recommends clinicians assess patients with diabetes for peripheral neuropathic pain and its effect on their function and quality of life.

Before prescribing treatment, health providers should determine if the patient also has mood or sleep problems as both can influence pain perception.

The guideline recommends offering one of four classes of oral medications found to be effective for neuropathic pain: tricyclic antidepressants such as amitriptyline, nortriptyline, or imipramine; serotonin norepinephrine reuptake inhibitors such as duloxetine, venlafaxine, or desvenlafaxine; gabapentinoids such as gabapentin or pregabalin; and/or sodium channel blockers such as carbamazepine, oxcarbazepine, lamotrigine, or lacosamide.

All four classes of medications have “comparable effect sizes just above or just below our cutoff for a medium effect size” (standardized median difference, 0.5), the panel noted.

In addition, “new studies on sodium channel blockers published since the last guideline have resulted in these drugs now being recommended and considered as effective at providing pain relief as the other drug classes recommended in this guideline,” said Dr. Callaghan.

When an initial medication fails to provide meaningful improvement in pain, or produces significant side effects, a trial of another medication from a different class is recommended.
 

Pain reduction, not elimination

Opioids are not recommended for painful diabetic neuropathy. Not only do they come with risks, there is also no strong evidence they are effective for painful diabetic neuropathy in the long term, the panel wrote. Tramadol and tapentadol are also not recommended for the treatment of painful diabetic neuropathy.

“Current evidence suggests that the risks of the use of opioids for painful diabetic neuropathy therapy outweigh the benefits, so they should not be prescribed,” Dr. Callaghan said.

For patients interested in trying topical, nontraditional, or nondrug interventions to reduce pain, the guideline recommends a number of options including capsaicin, glyceryl trinitrate spray, and Citrullus colocynthis. Ginkgo biloba, exercise, mindfulness, cognitive-behavioral therapy, and tai chi are also suggested.

“It is important to note that the recommended drugs and topical treatments in this guideline may not eliminate pain, but they have been shown to reduce pain,” Dr. Callaghan said. “The good news is there are many treatment options for painful diabetic neuropathy, so a treatment plan can be tailored specifically to each person living with this condition.”

Along with the updated guideline, the AAN has also published a new Polyneuropathy Quality Measurement Set to assist neurologists and other health care providers in treating patients with painful diabetic neuropathy.

The updated guideline was developed with financial support from the AAN.

A version of this article first appeared on Medscape.com.

A traumatic brain injury (TBI), even a mild type, can lead to posttraumatic epilepsy up to 1 year after the head injury occurs, new research suggests.

Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.

“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.

Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”

The findings were published online Dec. 29 in JAMA Network Open.
 

Novel study

Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.

To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.

The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.

The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.

The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
 

Confirmatory data

Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.

Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.

The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).

This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.

Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.

“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.

The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.

“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
 

Universal screening?

The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.

Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.

Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.

What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.

The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.

The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.

A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.

The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.

A version of this article first appeared on Medscape.com.

A traumatic brain injury (TBI), even a mild type, can lead to posttraumatic epilepsy up to 1 year after the head injury occurs, new research suggests.

Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.

“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.

Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”

The findings were published online Dec. 29 in JAMA Network Open.
 

Novel study

Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.

To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.

The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.

The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.

The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
 

Confirmatory data

Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.

Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.

The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).

This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.

Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.

“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.

The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.

“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
 

Universal screening?

The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.

Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.

Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.

What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.

The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.

The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.

A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.

The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.

A version of this article first appeared on Medscape.com.

A traumatic brain injury (TBI), even a mild type, can lead to posttraumatic epilepsy up to 1 year after the head injury occurs, new research suggests.

Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.

“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.

Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”

The findings were published online Dec. 29 in JAMA Network Open.
 

Novel study

Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.

To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.

The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.

The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.

The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
 

Confirmatory data

Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.

Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.

The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).

This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.

Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.

“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.

The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.

“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
 

Universal screening?

The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.

Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.

Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.

What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.

The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.

The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.

A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.

The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.

A version of this article first appeared on Medscape.com.

People who have had prior SARS-CoV-2 infection report significantly more symptoms of cognitive dysfunction and specifically executive dysfunction than people in the general population with no such infection, according to new data published on the preprint server medRxiv.

Researchers, led by Peter A. Hall, PhD, with the University of Waterloo (Ont.), found that COVID infection is associated with executive dysfunction among young and middle-aged adults, including for those not exposed to intubation or hospitalization.

The findings have not been peer reviewed.

The study included a representative cohort of 1,958 community-dwelling young and middle-aged adults. It used a balanced proportion of infected and uninfected people to estimate the link between SARS-CoV-2 infection and cognitive/executive dysfunction.

The authors noted that the survey was conducted from Sept. 28 to Oct. 21, 2021, when the primary variant in Canada was Delta.

The research was a cross-sectional observational study with data from the ongoing Canadian COVID-19 Experiences Survey. It included equal representation of vaccinated and vaccine-hesitant adults aged 18-54 years. COVID-19 symptoms ranged from negligible to life-threatening cases requiring hospitalization.

Half in the cohort (50.2%) received two vaccine shots; 43.3% had received no shots; and 5.5% received one shot, but were not intending to receive a second shot.
 

Dose-response relationship

According to the paper, those with prior COVID-19 infection, regardless of symptom severity, reported a significantly higher number of symptoms of executive dysfunction than their noninfected counterparts (mechanical adjustment, 1.63, standard error, 0.08; 95% confidence interval, 1.47-1.80; P = .001).

The researchers also found a dose-response relationship between COVID-19 symptom severity and cognitive dysfunction. Those with moderate and very/extremely severe COVID-19 symptoms were linked with significantly greater dysfunction.

“This reinforces what we’re hearing about – that COVID is not ‘one and done.’ It can have lasting and quite subtle and damaging effects on the human body,” William Schaffner, MD, infectious disease specialist with Vanderbilt University, Nashville, Tenn., said in an interview.

Measuring executive functioning – including the ability to make sound decisions – is something other studies haven’t typically addressed, he said.

Men were likely to report more cognitive dysfunction symptoms than women (beta, 0.15; P < .001). Younger adults (25-39 years) were more likely to experience cognitive dysfunction than those age 40-54 (beta, 0.30; P < .001).

Dr. Schaffner said it was troubling that young people are more likely to experience the dysfunction.

“When we think of ‘brain fog’ we think of older persons who are already predisposed to have more memory lapses as they get older,” he said.

The link between cognitive dysfunction and COVID-19 infection has been shown in other studies, but many have not used representative samples and have not compared results with noninfected controls in the general population, the authors wrote.

Executive dysfunction was measured using four questions from the Deficits in Executive Functioning Scale. Respondents were asked how often they have experienced these scenarios in the past 6 months:
 

• “I am unable to inhibit my reactions or responses to events or to other people.”
• “I make impulsive comments to others.”
• “I am likely to do things without considering the consequences for doing them.”
• “I act without thinking.”

“This makes it even more important that we talk about vaccination,” Dr. Schaffner said, “because clearly the more seriously ill you are, the more likely this sort of thing is likely to happen and vaccines have been shown time and again to avert hospitalizations and more serious illness. It also makes more important the monoclonal antibody treatments we have and the antivirals, which will prevent the evolution of mild disease into something more serious.”

This research was supported by a grant from the Canadian Institutes for Health Research, Institute for Population and Public Health. The study authors and Dr. Schaffner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have had prior SARS-CoV-2 infection report significantly more symptoms of cognitive dysfunction and specifically executive dysfunction than people in the general population with no such infection, according to new data published on the preprint server medRxiv.

Researchers, led by Peter A. Hall, PhD, with the University of Waterloo (Ont.), found that COVID infection is associated with executive dysfunction among young and middle-aged adults, including for those not exposed to intubation or hospitalization.

The findings have not been peer reviewed.

The study included a representative cohort of 1,958 community-dwelling young and middle-aged adults. It used a balanced proportion of infected and uninfected people to estimate the link between SARS-CoV-2 infection and cognitive/executive dysfunction.

The authors noted that the survey was conducted from Sept. 28 to Oct. 21, 2021, when the primary variant in Canada was Delta.

The research was a cross-sectional observational study with data from the ongoing Canadian COVID-19 Experiences Survey. It included equal representation of vaccinated and vaccine-hesitant adults aged 18-54 years. COVID-19 symptoms ranged from negligible to life-threatening cases requiring hospitalization.

Half in the cohort (50.2%) received two vaccine shots; 43.3% had received no shots; and 5.5% received one shot, but were not intending to receive a second shot.
 

Dose-response relationship

According to the paper, those with prior COVID-19 infection, regardless of symptom severity, reported a significantly higher number of symptoms of executive dysfunction than their noninfected counterparts (mechanical adjustment, 1.63, standard error, 0.08; 95% confidence interval, 1.47-1.80; P = .001).

The researchers also found a dose-response relationship between COVID-19 symptom severity and cognitive dysfunction. Those with moderate and very/extremely severe COVID-19 symptoms were linked with significantly greater dysfunction.

“This reinforces what we’re hearing about – that COVID is not ‘one and done.’ It can have lasting and quite subtle and damaging effects on the human body,” William Schaffner, MD, infectious disease specialist with Vanderbilt University, Nashville, Tenn., said in an interview.

Measuring executive functioning – including the ability to make sound decisions – is something other studies haven’t typically addressed, he said.

Men were likely to report more cognitive dysfunction symptoms than women (beta, 0.15; P < .001). Younger adults (25-39 years) were more likely to experience cognitive dysfunction than those age 40-54 (beta, 0.30; P < .001).

Dr. Schaffner said it was troubling that young people are more likely to experience the dysfunction.

“When we think of ‘brain fog’ we think of older persons who are already predisposed to have more memory lapses as they get older,” he said.

The link between cognitive dysfunction and COVID-19 infection has been shown in other studies, but many have not used representative samples and have not compared results with noninfected controls in the general population, the authors wrote.

Executive dysfunction was measured using four questions from the Deficits in Executive Functioning Scale. Respondents were asked how often they have experienced these scenarios in the past 6 months:
 

• “I am unable to inhibit my reactions or responses to events or to other people.”
• “I make impulsive comments to others.”
• “I am likely to do things without considering the consequences for doing them.”
• “I act without thinking.”

“This makes it even more important that we talk about vaccination,” Dr. Schaffner said, “because clearly the more seriously ill you are, the more likely this sort of thing is likely to happen and vaccines have been shown time and again to avert hospitalizations and more serious illness. It also makes more important the monoclonal antibody treatments we have and the antivirals, which will prevent the evolution of mild disease into something more serious.”

This research was supported by a grant from the Canadian Institutes for Health Research, Institute for Population and Public Health. The study authors and Dr. Schaffner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have had prior SARS-CoV-2 infection report significantly more symptoms of cognitive dysfunction and specifically executive dysfunction than people in the general population with no such infection, according to new data published on the preprint server medRxiv.

Researchers, led by Peter A. Hall, PhD, with the University of Waterloo (Ont.), found that COVID infection is associated with executive dysfunction among young and middle-aged adults, including for those not exposed to intubation or hospitalization.

The findings have not been peer reviewed.

The study included a representative cohort of 1,958 community-dwelling young and middle-aged adults. It used a balanced proportion of infected and uninfected people to estimate the link between SARS-CoV-2 infection and cognitive/executive dysfunction.

The authors noted that the survey was conducted from Sept. 28 to Oct. 21, 2021, when the primary variant in Canada was Delta.

The research was a cross-sectional observational study with data from the ongoing Canadian COVID-19 Experiences Survey. It included equal representation of vaccinated and vaccine-hesitant adults aged 18-54 years. COVID-19 symptoms ranged from negligible to life-threatening cases requiring hospitalization.

Half in the cohort (50.2%) received two vaccine shots; 43.3% had received no shots; and 5.5% received one shot, but were not intending to receive a second shot.
 

Dose-response relationship

According to the paper, those with prior COVID-19 infection, regardless of symptom severity, reported a significantly higher number of symptoms of executive dysfunction than their noninfected counterparts (mechanical adjustment, 1.63, standard error, 0.08; 95% confidence interval, 1.47-1.80; P = .001).

The researchers also found a dose-response relationship between COVID-19 symptom severity and cognitive dysfunction. Those with moderate and very/extremely severe COVID-19 symptoms were linked with significantly greater dysfunction.

“This reinforces what we’re hearing about – that COVID is not ‘one and done.’ It can have lasting and quite subtle and damaging effects on the human body,” William Schaffner, MD, infectious disease specialist with Vanderbilt University, Nashville, Tenn., said in an interview.

Measuring executive functioning – including the ability to make sound decisions – is something other studies haven’t typically addressed, he said.

Men were likely to report more cognitive dysfunction symptoms than women (beta, 0.15; P < .001). Younger adults (25-39 years) were more likely to experience cognitive dysfunction than those age 40-54 (beta, 0.30; P < .001).

Dr. Schaffner said it was troubling that young people are more likely to experience the dysfunction.

“When we think of ‘brain fog’ we think of older persons who are already predisposed to have more memory lapses as they get older,” he said.

The link between cognitive dysfunction and COVID-19 infection has been shown in other studies, but many have not used representative samples and have not compared results with noninfected controls in the general population, the authors wrote.

Executive dysfunction was measured using four questions from the Deficits in Executive Functioning Scale. Respondents were asked how often they have experienced these scenarios in the past 6 months:
 

• “I am unable to inhibit my reactions or responses to events or to other people.”
• “I make impulsive comments to others.”
• “I am likely to do things without considering the consequences for doing them.”
• “I act without thinking.”

“This makes it even more important that we talk about vaccination,” Dr. Schaffner said, “because clearly the more seriously ill you are, the more likely this sort of thing is likely to happen and vaccines have been shown time and again to avert hospitalizations and more serious illness. It also makes more important the monoclonal antibody treatments we have and the antivirals, which will prevent the evolution of mild disease into something more serious.”

This research was supported by a grant from the Canadian Institutes for Health Research, Institute for Population and Public Health. The study authors and Dr. Schaffner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.