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In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.

By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.

So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.

However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.

And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.

Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”

In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”

In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.

A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.

Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”

As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).

In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”

Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.

In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get. 

In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.

By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.

So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.

However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.

And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.

Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”

In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”

In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.

A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.

Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”

As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).

In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”

Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.

In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get. 

In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.

By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.

So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.

However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.

And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.

Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”

In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”

In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.

A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.

Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”

As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).

In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”

Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.

In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get. 

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.

Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.

Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.

The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.

The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.

In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.

In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.

“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.

In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.

Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.

“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”

Feinstein Institutes for Medical Research

According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”

In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.

Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.

“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”

These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.

More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”

This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
 

Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.

Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.

The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.

The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.

In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.

In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.

“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.

In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.

Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.

“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”

Feinstein Institutes for Medical Research

According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”

In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.

Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.

“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”

These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.

More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”

This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
 

Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.

Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.

The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.

The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.

In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.

In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.

“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.

In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.

Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.

“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”

Feinstein Institutes for Medical Research

According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”

In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.

Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.

“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”

These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.

More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”

This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
 

The antidepressant bupropion failed to improve sexual dysfunction in female cancer survivors, according to new findings published online in the Journal of Clinical Oncology.

Using the Female Sexual Function Index (FSFI) as a measurement tool, investigators found that desire scores were not significantly different for participants who received bupropion versus a placebo over the 9-week study period.

“Sexual health is a complex phenomenon and [our results suggest that] no one intervention is going to solve the broader issue,” lead author Debra Barton, RN, PhD, FAAN, professor in the School of Nursing at the University of Michigan, Ann Arbor, told this news organization.

Sexual dysfunction is common among cancer survivors and experienced across multiple cancer types and stages of disease. Research shows that as many as 70% of female cancer survivors report loss of desire, compared with up to one-third of the general population.

Common sexual concerns among female cancer survivors include low desire, arousal issues, lack of appropriate lubrication, difficulty in achieving orgasm, and pain with penetrative sexual activity. Additionally, these women may experience significant overlap of symptoms, and often encounter multiple sexual issues that are exacerbated by a range of cancer treatments.

“It’s a huge problem,” Maryam B. Lustberg, MD, MPH, from Yale Cancer Center, New Haven, Conn., and colleagues wrote in an accompanying editorial.

Despite the prevalence of sexual dysfunction among cancer survivors, effective treatments remain elusive. Preliminary evidence suggests that bupropion, already approved for seasonal affective disorder, major depressive disorder, and smoking cessation, may also enhance libido.

Dr. Barton and colleagues conducted this phase 2 trial to determine whether bupropion can improve sexual desire in female cancer survivors without undesirable side effects.

In the study, Dr. Barton and colleagues compared two dose levels of extended-release bupropion in a cohort of 230 postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (<3.3), who had completed definitive cancer therapy.

Participants were randomized to receive either 150 mg (79 patients) or 300 mg (74 patients) once daily of extended-release bupropion, or placebo (77 patients).

Barton and colleagues then evaluated whether sexual desire significantly improved over the 9-week study period comparing the bupropion arms and the placebo group.

Overall, the authors found no significant differences (mean between-arm change for 150 mg once daily and placebo of 0.02; P = .93; mean between-arm change for 300 mg once daily and placebo of –0.02; P = .92). Mean scores at 9 weeks on the desire subscale were 2.17, 2.27, and 2.30 for 150 mg, 300 mg, and the placebo group, respectively.

In addition, none of the subscales – which included arousal, lubrication, and orgasm – or the total score showed a significant difference between arms at either 5 or 9 weeks.

Bupropion did, however, appear to be well tolerated. No grade 4-5 treatment-related adverse events occurred. In the 150-mg bupropion arm, two patients (2.6%) experienced a grade 3 event (insomnia and headache) and one patient in the 300-mg bupropion arm (1.4%) and placebo arm (1.3%) experienced a grade 3 event related to treatment (hypertension and headache, respectively).

In the accompanying editorial, Dr. Lustberg and colleagues “applaud the authors for conducting a study in this population of cancer survivors,” noting that “evidenced-based approaches have not been extensively studied.”

Dr. Lustberg and colleagues also commented that other randomized controlled clinical trials evaluating sexual desire disorder assessed outcomes using additional metrics, such as the Female Sexual Distress Scale–Revised questionnaire, which measures distress related to sexual dysfunction and low desire, in particular.

“The use of specific validated instruments for libido in place of the FSFI might have helped determine the effect of the study intervention in this reported trial,” they wrote.

Overall, according to Dr. Lustberg and colleagues, the negative results of this study indicate that a multidisciplinary clinical approach may be needed.

“As much as we would like to have one intervention that addresses this prominent issue, the evidence strongly suggests that cancer-related sexual problems may need an integrative biopsychosocial model that intervenes on biologic, psychologic, interpersonal, and social-cultural factors, not just on one factor, such as libido,” they wrote. “Such work may require access to multidisciplinary care with specialists in women’s health, pelvic floor rehabilitation, and psychosocial oncology.”

Dr. Barton said she has been developing a multicomponent approach to addressing sexual health in female cancer survivors.

However, she noted, “there is still much we do not fully understand about the broader impact of the degree of hormone deprivation in the population of female cancer survivors. A better understanding would provide clearer targets for interventions.” 

The study was supported by the National Cancer Institute and Breast Cancer Research Foundation. Dr. Barton has disclosed research funding from Merck. Dr. Lustberg reported receiving honoraria from Novartis and Biotheranostics; consulting or advising with PledPharma, Disarm Therapeutics, Pfizer; and other relationships with Cynosure/Hologic.

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

The antidepressant bupropion failed to improve sexual dysfunction in female cancer survivors, according to new findings published online in the Journal of Clinical Oncology.

Using the Female Sexual Function Index (FSFI) as a measurement tool, investigators found that desire scores were not significantly different for participants who received bupropion versus a placebo over the 9-week study period.

“Sexual health is a complex phenomenon and [our results suggest that] no one intervention is going to solve the broader issue,” lead author Debra Barton, RN, PhD, FAAN, professor in the School of Nursing at the University of Michigan, Ann Arbor, told this news organization.

Sexual dysfunction is common among cancer survivors and experienced across multiple cancer types and stages of disease. Research shows that as many as 70% of female cancer survivors report loss of desire, compared with up to one-third of the general population.

Common sexual concerns among female cancer survivors include low desire, arousal issues, lack of appropriate lubrication, difficulty in achieving orgasm, and pain with penetrative sexual activity. Additionally, these women may experience significant overlap of symptoms, and often encounter multiple sexual issues that are exacerbated by a range of cancer treatments.

“It’s a huge problem,” Maryam B. Lustberg, MD, MPH, from Yale Cancer Center, New Haven, Conn., and colleagues wrote in an accompanying editorial.

Despite the prevalence of sexual dysfunction among cancer survivors, effective treatments remain elusive. Preliminary evidence suggests that bupropion, already approved for seasonal affective disorder, major depressive disorder, and smoking cessation, may also enhance libido.

Dr. Barton and colleagues conducted this phase 2 trial to determine whether bupropion can improve sexual desire in female cancer survivors without undesirable side effects.

In the study, Dr. Barton and colleagues compared two dose levels of extended-release bupropion in a cohort of 230 postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (<3.3), who had completed definitive cancer therapy.

Participants were randomized to receive either 150 mg (79 patients) or 300 mg (74 patients) once daily of extended-release bupropion, or placebo (77 patients).

Barton and colleagues then evaluated whether sexual desire significantly improved over the 9-week study period comparing the bupropion arms and the placebo group.

Overall, the authors found no significant differences (mean between-arm change for 150 mg once daily and placebo of 0.02; P = .93; mean between-arm change for 300 mg once daily and placebo of –0.02; P = .92). Mean scores at 9 weeks on the desire subscale were 2.17, 2.27, and 2.30 for 150 mg, 300 mg, and the placebo group, respectively.

In addition, none of the subscales – which included arousal, lubrication, and orgasm – or the total score showed a significant difference between arms at either 5 or 9 weeks.

Bupropion did, however, appear to be well tolerated. No grade 4-5 treatment-related adverse events occurred. In the 150-mg bupropion arm, two patients (2.6%) experienced a grade 3 event (insomnia and headache) and one patient in the 300-mg bupropion arm (1.4%) and placebo arm (1.3%) experienced a grade 3 event related to treatment (hypertension and headache, respectively).

In the accompanying editorial, Dr. Lustberg and colleagues “applaud the authors for conducting a study in this population of cancer survivors,” noting that “evidenced-based approaches have not been extensively studied.”

Dr. Lustberg and colleagues also commented that other randomized controlled clinical trials evaluating sexual desire disorder assessed outcomes using additional metrics, such as the Female Sexual Distress Scale–Revised questionnaire, which measures distress related to sexual dysfunction and low desire, in particular.

“The use of specific validated instruments for libido in place of the FSFI might have helped determine the effect of the study intervention in this reported trial,” they wrote.

Overall, according to Dr. Lustberg and colleagues, the negative results of this study indicate that a multidisciplinary clinical approach may be needed.

“As much as we would like to have one intervention that addresses this prominent issue, the evidence strongly suggests that cancer-related sexual problems may need an integrative biopsychosocial model that intervenes on biologic, psychologic, interpersonal, and social-cultural factors, not just on one factor, such as libido,” they wrote. “Such work may require access to multidisciplinary care with specialists in women’s health, pelvic floor rehabilitation, and psychosocial oncology.”

Dr. Barton said she has been developing a multicomponent approach to addressing sexual health in female cancer survivors.

However, she noted, “there is still much we do not fully understand about the broader impact of the degree of hormone deprivation in the population of female cancer survivors. A better understanding would provide clearer targets for interventions.” 

The study was supported by the National Cancer Institute and Breast Cancer Research Foundation. Dr. Barton has disclosed research funding from Merck. Dr. Lustberg reported receiving honoraria from Novartis and Biotheranostics; consulting or advising with PledPharma, Disarm Therapeutics, Pfizer; and other relationships with Cynosure/Hologic.

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

The antidepressant bupropion failed to improve sexual dysfunction in female cancer survivors, according to new findings published online in the Journal of Clinical Oncology.

Using the Female Sexual Function Index (FSFI) as a measurement tool, investigators found that desire scores were not significantly different for participants who received bupropion versus a placebo over the 9-week study period.

“Sexual health is a complex phenomenon and [our results suggest that] no one intervention is going to solve the broader issue,” lead author Debra Barton, RN, PhD, FAAN, professor in the School of Nursing at the University of Michigan, Ann Arbor, told this news organization.

Sexual dysfunction is common among cancer survivors and experienced across multiple cancer types and stages of disease. Research shows that as many as 70% of female cancer survivors report loss of desire, compared with up to one-third of the general population.

Common sexual concerns among female cancer survivors include low desire, arousal issues, lack of appropriate lubrication, difficulty in achieving orgasm, and pain with penetrative sexual activity. Additionally, these women may experience significant overlap of symptoms, and often encounter multiple sexual issues that are exacerbated by a range of cancer treatments.

“It’s a huge problem,” Maryam B. Lustberg, MD, MPH, from Yale Cancer Center, New Haven, Conn., and colleagues wrote in an accompanying editorial.

Despite the prevalence of sexual dysfunction among cancer survivors, effective treatments remain elusive. Preliminary evidence suggests that bupropion, already approved for seasonal affective disorder, major depressive disorder, and smoking cessation, may also enhance libido.

Dr. Barton and colleagues conducted this phase 2 trial to determine whether bupropion can improve sexual desire in female cancer survivors without undesirable side effects.

In the study, Dr. Barton and colleagues compared two dose levels of extended-release bupropion in a cohort of 230 postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (<3.3), who had completed definitive cancer therapy.

Participants were randomized to receive either 150 mg (79 patients) or 300 mg (74 patients) once daily of extended-release bupropion, or placebo (77 patients).

Barton and colleagues then evaluated whether sexual desire significantly improved over the 9-week study period comparing the bupropion arms and the placebo group.

Overall, the authors found no significant differences (mean between-arm change for 150 mg once daily and placebo of 0.02; P = .93; mean between-arm change for 300 mg once daily and placebo of –0.02; P = .92). Mean scores at 9 weeks on the desire subscale were 2.17, 2.27, and 2.30 for 150 mg, 300 mg, and the placebo group, respectively.

In addition, none of the subscales – which included arousal, lubrication, and orgasm – or the total score showed a significant difference between arms at either 5 or 9 weeks.

Bupropion did, however, appear to be well tolerated. No grade 4-5 treatment-related adverse events occurred. In the 150-mg bupropion arm, two patients (2.6%) experienced a grade 3 event (insomnia and headache) and one patient in the 300-mg bupropion arm (1.4%) and placebo arm (1.3%) experienced a grade 3 event related to treatment (hypertension and headache, respectively).

In the accompanying editorial, Dr. Lustberg and colleagues “applaud the authors for conducting a study in this population of cancer survivors,” noting that “evidenced-based approaches have not been extensively studied.”

Dr. Lustberg and colleagues also commented that other randomized controlled clinical trials evaluating sexual desire disorder assessed outcomes using additional metrics, such as the Female Sexual Distress Scale–Revised questionnaire, which measures distress related to sexual dysfunction and low desire, in particular.

“The use of specific validated instruments for libido in place of the FSFI might have helped determine the effect of the study intervention in this reported trial,” they wrote.

Overall, according to Dr. Lustberg and colleagues, the negative results of this study indicate that a multidisciplinary clinical approach may be needed.

“As much as we would like to have one intervention that addresses this prominent issue, the evidence strongly suggests that cancer-related sexual problems may need an integrative biopsychosocial model that intervenes on biologic, psychologic, interpersonal, and social-cultural factors, not just on one factor, such as libido,” they wrote. “Such work may require access to multidisciplinary care with specialists in women’s health, pelvic floor rehabilitation, and psychosocial oncology.”

Dr. Barton said she has been developing a multicomponent approach to addressing sexual health in female cancer survivors.

However, she noted, “there is still much we do not fully understand about the broader impact of the degree of hormone deprivation in the population of female cancer survivors. A better understanding would provide clearer targets for interventions.” 

The study was supported by the National Cancer Institute and Breast Cancer Research Foundation. Dr. Barton has disclosed research funding from Merck. Dr. Lustberg reported receiving honoraria from Novartis and Biotheranostics; consulting or advising with PledPharma, Disarm Therapeutics, Pfizer; and other relationships with Cynosure/Hologic.

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

Although teledermatology utilization in the United States traditionally has lagged behind other countries,^1,2 the COVID-19 pandemic upended this trend by creating the need for a massive teledermatology experiment. Recently reported survey results from a large representative sample of US dermatologists (5000 participants) on perceptions of teledermatology during COVID-19 indicated that only 14.1% of participants used teledermatology prior to the COVID-19 pandemic vs 54.1% of dermatologists in Europe.^2,3 Since the pandemic started, 97% of US dermatologists reported teledermatology use,³ demonstrating a huge shift in utilization. This trend is notable, as teledermatology has been shown to increase access to dermatology in underserved areas, reduce patient travel times, improve patient triage, and even reduce carbon footprints.^1,4 Thus, to sustain the momentum, insights from the recent teledermatology experience during the pandemic should inform future development.

Notably, the COVID-19 pandemic led to a rapid shift in focus from store-and-forward teledermatology to live video–based models.^1,2 Logistically, live video visits are challenging, require more time and resources, and often are diagnostically limited, with concerns regarding technology, connectivity, reimbursement, and appropriate use.³ Prior to COVID-19, formal Health Insurance Portability and Accountability Act–compliant teledermatology platforms often were costly to establish and maintain, largely relegating use to academic centers and Veterans Affairs hospitals. Thus, many fewer private practice dermatologists had used teledermatology compared to academic dermatologists in the United States (11.4% vs 27.6%).³ Government regulations—a key barrier to the adoption of teledermatology in private practice before COVID-19—were greatly relaxed during the pandemic. The Centers for Medicare and Medicaid Services removed restrictions on where patients could be seen, improved reimbursement for video visits, and allowed the use of platforms that are not Health Insurance Portability and Accountability Act compliant. Many states also relaxed medical licensing rules.

Overall, the general outlook on telehealth seems positive. Reimbursement has been found to be a primary factor in dermatologists’ willingness to use teledermatology.³ Thus, sustainable use of teledermatology likely will depend on continued reimbursement parity for live video as well as store-and-forward consultations, which have several advantages but currently are de-incentivized by low reimbursement. The survey also found that 70% of respondents felt that teledermatology use will continue after COVID-19, while 58% intended to continue use—nearly 5-fold more than before the pandemic.³ We suspect the discrepancy between participants’ predictions regarding future use of teledermatology and their personal intent to use it highlights perceived barriers and limitations of the long-term success of teledermatology. Aside from reimbursement, connectivity and functionality were common concerns, emphasizing the need for innovative technological solutions.³ Moving forward, we anticipate that dermatologists will need to establish consistent workflows to establish consistent triage for the most appropriate visit—in-person visits vs teledermatology, which may include augmented, intelligence-enhanced solutions. Similar to prior clinician perspectives about which types of visits are conducive to teledermatology,² most survey participants believed virtual visits were effective for acne, routine follow-ups, medication monitoring, and some inflammatory conditions.³

Importantly, we must be mindful of patients who may be left behind by the digital divide, such as those with lack of access to a smartphone or the internet, language barriers, or limited telehealth experience.⁵ Systems should be designed to provide these patients with technologic and health literacy aid or alternate modalities to access care. For example, structured methods could be introduced to provide training and instructions on how to access phone applications, computer-based programs, and more. Likewise, for those with hearing or vision deficits, it will be important to improve sound amplification and accessibility for headphones or hearing aid connectivity, as well as appropriate font size, button size, and application navigation. In remote areas, existing clinics may be used to help field specialty consultation teleconferences. Certainly, applications and platforms devised for teledermatology must be designed to serve diverse patient groups, with special consideration for the elderly, those who speak languages other than English, and those with disabilities that may make telehealth use more challenging.

Large-scale regulatory changes and reimbursement parity can have a substantial impact on future teledermatology use. Advocacy efforts continue to push for fair valuation of telemedicine, coverage of store-and-forward teledermatology codes, and coverage for all models of care. It is imperative for the dermatology community to continue discussions on implementation and methodology to best leverage this technology for the most patient benefit.

Although teledermatology utilization in the United States traditionally has lagged behind other countries,^1,2 the COVID-19 pandemic upended this trend by creating the need for a massive teledermatology experiment. Recently reported survey results from a large representative sample of US dermatologists (5000 participants) on perceptions of teledermatology during COVID-19 indicated that only 14.1% of participants used teledermatology prior to the COVID-19 pandemic vs 54.1% of dermatologists in Europe.^2,3 Since the pandemic started, 97% of US dermatologists reported teledermatology use,³ demonstrating a huge shift in utilization. This trend is notable, as teledermatology has been shown to increase access to dermatology in underserved areas, reduce patient travel times, improve patient triage, and even reduce carbon footprints.^1,4 Thus, to sustain the momentum, insights from the recent teledermatology experience during the pandemic should inform future development.

Notably, the COVID-19 pandemic led to a rapid shift in focus from store-and-forward teledermatology to live video–based models.^1,2 Logistically, live video visits are challenging, require more time and resources, and often are diagnostically limited, with concerns regarding technology, connectivity, reimbursement, and appropriate use.³ Prior to COVID-19, formal Health Insurance Portability and Accountability Act–compliant teledermatology platforms often were costly to establish and maintain, largely relegating use to academic centers and Veterans Affairs hospitals. Thus, many fewer private practice dermatologists had used teledermatology compared to academic dermatologists in the United States (11.4% vs 27.6%).³ Government regulations—a key barrier to the adoption of teledermatology in private practice before COVID-19—were greatly relaxed during the pandemic. The Centers for Medicare and Medicaid Services removed restrictions on where patients could be seen, improved reimbursement for video visits, and allowed the use of platforms that are not Health Insurance Portability and Accountability Act compliant. Many states also relaxed medical licensing rules.

Overall, the general outlook on telehealth seems positive. Reimbursement has been found to be a primary factor in dermatologists’ willingness to use teledermatology.³ Thus, sustainable use of teledermatology likely will depend on continued reimbursement parity for live video as well as store-and-forward consultations, which have several advantages but currently are de-incentivized by low reimbursement. The survey also found that 70% of respondents felt that teledermatology use will continue after COVID-19, while 58% intended to continue use—nearly 5-fold more than before the pandemic.³ We suspect the discrepancy between participants’ predictions regarding future use of teledermatology and their personal intent to use it highlights perceived barriers and limitations of the long-term success of teledermatology. Aside from reimbursement, connectivity and functionality were common concerns, emphasizing the need for innovative technological solutions.³ Moving forward, we anticipate that dermatologists will need to establish consistent workflows to establish consistent triage for the most appropriate visit—in-person visits vs teledermatology, which may include augmented, intelligence-enhanced solutions. Similar to prior clinician perspectives about which types of visits are conducive to teledermatology,² most survey participants believed virtual visits were effective for acne, routine follow-ups, medication monitoring, and some inflammatory conditions.³

Importantly, we must be mindful of patients who may be left behind by the digital divide, such as those with lack of access to a smartphone or the internet, language barriers, or limited telehealth experience.⁵ Systems should be designed to provide these patients with technologic and health literacy aid or alternate modalities to access care. For example, structured methods could be introduced to provide training and instructions on how to access phone applications, computer-based programs, and more. Likewise, for those with hearing or vision deficits, it will be important to improve sound amplification and accessibility for headphones or hearing aid connectivity, as well as appropriate font size, button size, and application navigation. In remote areas, existing clinics may be used to help field specialty consultation teleconferences. Certainly, applications and platforms devised for teledermatology must be designed to serve diverse patient groups, with special consideration for the elderly, those who speak languages other than English, and those with disabilities that may make telehealth use more challenging.

Large-scale regulatory changes and reimbursement parity can have a substantial impact on future teledermatology use. Advocacy efforts continue to push for fair valuation of telemedicine, coverage of store-and-forward teledermatology codes, and coverage for all models of care. It is imperative for the dermatology community to continue discussions on implementation and methodology to best leverage this technology for the most patient benefit.

Although teledermatology utilization in the United States traditionally has lagged behind other countries,^1,2 the COVID-19 pandemic upended this trend by creating the need for a massive teledermatology experiment. Recently reported survey results from a large representative sample of US dermatologists (5000 participants) on perceptions of teledermatology during COVID-19 indicated that only 14.1% of participants used teledermatology prior to the COVID-19 pandemic vs 54.1% of dermatologists in Europe.^2,3 Since the pandemic started, 97% of US dermatologists reported teledermatology use,³ demonstrating a huge shift in utilization. This trend is notable, as teledermatology has been shown to increase access to dermatology in underserved areas, reduce patient travel times, improve patient triage, and even reduce carbon footprints.^1,4 Thus, to sustain the momentum, insights from the recent teledermatology experience during the pandemic should inform future development.

Notably, the COVID-19 pandemic led to a rapid shift in focus from store-and-forward teledermatology to live video–based models.^1,2 Logistically, live video visits are challenging, require more time and resources, and often are diagnostically limited, with concerns regarding technology, connectivity, reimbursement, and appropriate use.³ Prior to COVID-19, formal Health Insurance Portability and Accountability Act–compliant teledermatology platforms often were costly to establish and maintain, largely relegating use to academic centers and Veterans Affairs hospitals. Thus, many fewer private practice dermatologists had used teledermatology compared to academic dermatologists in the United States (11.4% vs 27.6%).³ Government regulations—a key barrier to the adoption of teledermatology in private practice before COVID-19—were greatly relaxed during the pandemic. The Centers for Medicare and Medicaid Services removed restrictions on where patients could be seen, improved reimbursement for video visits, and allowed the use of platforms that are not Health Insurance Portability and Accountability Act compliant. Many states also relaxed medical licensing rules.

Overall, the general outlook on telehealth seems positive. Reimbursement has been found to be a primary factor in dermatologists’ willingness to use teledermatology.³ Thus, sustainable use of teledermatology likely will depend on continued reimbursement parity for live video as well as store-and-forward consultations, which have several advantages but currently are de-incentivized by low reimbursement. The survey also found that 70% of respondents felt that teledermatology use will continue after COVID-19, while 58% intended to continue use—nearly 5-fold more than before the pandemic.³ We suspect the discrepancy between participants’ predictions regarding future use of teledermatology and their personal intent to use it highlights perceived barriers and limitations of the long-term success of teledermatology. Aside from reimbursement, connectivity and functionality were common concerns, emphasizing the need for innovative technological solutions.³ Moving forward, we anticipate that dermatologists will need to establish consistent workflows to establish consistent triage for the most appropriate visit—in-person visits vs teledermatology, which may include augmented, intelligence-enhanced solutions. Similar to prior clinician perspectives about which types of visits are conducive to teledermatology,² most survey participants believed virtual visits were effective for acne, routine follow-ups, medication monitoring, and some inflammatory conditions.³

Importantly, we must be mindful of patients who may be left behind by the digital divide, such as those with lack of access to a smartphone or the internet, language barriers, or limited telehealth experience.⁵ Systems should be designed to provide these patients with technologic and health literacy aid or alternate modalities to access care. For example, structured methods could be introduced to provide training and instructions on how to access phone applications, computer-based programs, and more. Likewise, for those with hearing or vision deficits, it will be important to improve sound amplification and accessibility for headphones or hearing aid connectivity, as well as appropriate font size, button size, and application navigation. In remote areas, existing clinics may be used to help field specialty consultation teleconferences. Certainly, applications and platforms devised for teledermatology must be designed to serve diverse patient groups, with special consideration for the elderly, those who speak languages other than English, and those with disabilities that may make telehealth use more challenging.

Large-scale regulatory changes and reimbursement parity can have a substantial impact on future teledermatology use. Advocacy efforts continue to push for fair valuation of telemedicine, coverage of store-and-forward teledermatology codes, and coverage for all models of care. It is imperative for the dermatology community to continue discussions on implementation and methodology to best leverage this technology for the most patient benefit.

A distinct pattern of frontal-temporal atrophy discernible on magnetic resonance imaging (MRI) may flag chronic traumatic encephalopathy (CTE) in living patients, new research suggests.

“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.

The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
 

A new way to diagnose?

CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.

There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).

The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.

The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.

Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).

From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
 

More atrophy

Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.

The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).

Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.

The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.

The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.

Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.

“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.

Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).

Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
 

An important first step

The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).

When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).

Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”

He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.

While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.

“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
 

‘Not unexpected’

Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”

Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.

The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.

Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.

Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
 

Overstated conclusion?

Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.

“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”

A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”

The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”

Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.

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

A distinct pattern of frontal-temporal atrophy discernible on magnetic resonance imaging (MRI) may flag chronic traumatic encephalopathy (CTE) in living patients, new research suggests.

“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.

The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
 

A new way to diagnose?

CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.

There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).

The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.

The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.

Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).

From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
 

More atrophy

Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.

The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).

Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.

The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.

The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.

Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.

“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.

Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).

Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
 

An important first step

The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).

When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).

Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”

He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.

While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.

“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
 

‘Not unexpected’

Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”

Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.

The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.

Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.

Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
 

Overstated conclusion?

Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.

“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”

A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”

The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”

Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.

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

A distinct pattern of frontal-temporal atrophy discernible on magnetic resonance imaging (MRI) may flag chronic traumatic encephalopathy (CTE) in living patients, new research suggests.

“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.

The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
 

A new way to diagnose?

CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.

There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).

The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.

The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.

Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).

From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
 

More atrophy

Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.

The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).

Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.

The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.

The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.

Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.

“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.

Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).

Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
 

An important first step

The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).

When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).

Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”

He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.

While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.

“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
 

‘Not unexpected’

Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”

Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.

The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.

Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.

Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
 

Overstated conclusion?

Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.

“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”

A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”

The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”

Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.

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.