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FDA expands indication for spinal muscular atrophy drug
As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.
The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.
After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.
Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.
All babies were alive at 12 months without permanent ventilation.
“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.
“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
From newborns to older adults?
SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.
SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.
Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.
As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.
“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release.
“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.
A version of this article first appeared on Medscape.com.
As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.
The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.
After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.
Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.
All babies were alive at 12 months without permanent ventilation.
“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.
“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
From newborns to older adults?
SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.
SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.
Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.
As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.
“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release.
“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.
A version of this article first appeared on Medscape.com.
As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.
The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.
After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.
Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.
All babies were alive at 12 months without permanent ventilation.
“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.
“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
From newborns to older adults?
SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.
SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.
Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.
As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.
“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release.
“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.
A version of this article first appeared on Medscape.com.
‘Double-edged’ impact of sparring on the brains of MMA fighters
, early research suggests.
Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.
“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.
“The combination of complex movements along with constant strategy and anticipation of your opponent’s next move may provide a neuroprotective effect on the caudate,” Mr. Esagoff said. However, he added, more research is needed into understanding this particular finding.
The study results were presented at the American Psychiatric Association (APA) 2022 Annual Meeting.
Growing popularity
MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.
To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.
The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.
As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.
Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.
The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.
The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
A ‘highly strategic’ sport
Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).
This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.
There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).
There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.
The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.
He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.
However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.
A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.
Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.
He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
Jury still out
Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.
“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.
He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.
Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.
“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.
A version of this article first appeared on Medscape.com.
, early research suggests.
Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.
“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.
“The combination of complex movements along with constant strategy and anticipation of your opponent’s next move may provide a neuroprotective effect on the caudate,” Mr. Esagoff said. However, he added, more research is needed into understanding this particular finding.
The study results were presented at the American Psychiatric Association (APA) 2022 Annual Meeting.
Growing popularity
MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.
To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.
The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.
As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.
Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.
The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.
The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
A ‘highly strategic’ sport
Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).
This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.
There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).
There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.
The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.
He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.
However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.
A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.
Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.
He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
Jury still out
Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.
“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.
He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.
Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.
“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.
A version of this article first appeared on Medscape.com.
, early research suggests.
Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.
“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.
“The combination of complex movements along with constant strategy and anticipation of your opponent’s next move may provide a neuroprotective effect on the caudate,” Mr. Esagoff said. However, he added, more research is needed into understanding this particular finding.
The study results were presented at the American Psychiatric Association (APA) 2022 Annual Meeting.
Growing popularity
MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.
To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.
The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.
As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.
Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.
The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.
The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
A ‘highly strategic’ sport
Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).
This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.
There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).
There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.
The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.
He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.
However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.
A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.
Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.
He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
Jury still out
Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.
“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.
He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.
Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.
“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.
A version of this article first appeared on Medscape.com.
FROM APA 2022
Duration of breastfeeding associated with cognition in children
Breastfeeding duration is associated with improved cognitive scores at ages 5-14, even after controlling for maternal socioeconomic position and cognitive ability, said the researchers behind a new study.
Despite previous studies demonstrating an association between breastfeeding and standardized intelligence test scores – with breastfed infants scoring higher on intelligence tests than non-breastfed infants – a causal relationship is still contested.
“There is some debate about whether breastfeeding a baby for a longer period of time improves their cognitive development,” the authors of the new study said. They went on to explain how improved cognitive outcomes in breastfed infants could potentially be explained by other characteristics of the women, such as “socioeconomics and maternal intelligence.”
Important at the population level
For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford (England) set out to investigate how much these confounders influenced the association between breastfeeding duration and cognitive development.
They analyzed data from the U.K. Millennium Cohort Study on 7,855 infants born in 2000 to 2002 and followed until age 14. They highlighted that although the cohort was not specifically designed to address the association between breastfeeding and cognition, it included information on duration of any breastfeeding, duration of exclusive breastfeeding, verbal cognitive scores at ages 5, 7, 11, and 14, spatial cognitive scores at ages 5, 7, and 11, as well as potential confounders, including socioeconomic characteristics and maternal cognition, based on a vocabulary test.
The researchers discovered that longer breastfeeding durations were associated with higher verbal and spatial cognitive scores at all ages up to 14 and 11, respectively.
After taking the differences in socioeconomic position and maternal cognitive ability into account, those children who were breastfed for longer scored higher in cognitive measures up to age 14, compared with children who were not breastfed. They also found that longer breastfeeding durations were associated with mean cognitive scores 0.08-0.26 standard deviations higher than the mean cognitive score of those who were never breastfed. “This difference may seem small for an individual child but could be important at the population level,” the authors commented.
Modest effect
In the United Kingdom, women who have more educational qualifications and are more economically advantaged tend to breastfeed for longer, said the authors. In addition, they added, this group tends to “score more highly on cognitive tests.”
These differences could explain why babies who breastfeed for longer do better in cognitive assessments. However, they said that in their study, “we found that even after taking these differences into account, children breastfed for longer scored higher in cognitive measures up to age 14, in comparison to children who were not breastfed.”
The authors explained that the association between breastfeeding duration and cognitive scores “persists after adjusting for socioeconomics and maternal intelligence.” However, they pointed out that “the effect was modest.”
A version of this article first appeared on Medscape UK.
Breastfeeding duration is associated with improved cognitive scores at ages 5-14, even after controlling for maternal socioeconomic position and cognitive ability, said the researchers behind a new study.
Despite previous studies demonstrating an association between breastfeeding and standardized intelligence test scores – with breastfed infants scoring higher on intelligence tests than non-breastfed infants – a causal relationship is still contested.
“There is some debate about whether breastfeeding a baby for a longer period of time improves their cognitive development,” the authors of the new study said. They went on to explain how improved cognitive outcomes in breastfed infants could potentially be explained by other characteristics of the women, such as “socioeconomics and maternal intelligence.”
Important at the population level
For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford (England) set out to investigate how much these confounders influenced the association between breastfeeding duration and cognitive development.
They analyzed data from the U.K. Millennium Cohort Study on 7,855 infants born in 2000 to 2002 and followed until age 14. They highlighted that although the cohort was not specifically designed to address the association between breastfeeding and cognition, it included information on duration of any breastfeeding, duration of exclusive breastfeeding, verbal cognitive scores at ages 5, 7, 11, and 14, spatial cognitive scores at ages 5, 7, and 11, as well as potential confounders, including socioeconomic characteristics and maternal cognition, based on a vocabulary test.
The researchers discovered that longer breastfeeding durations were associated with higher verbal and spatial cognitive scores at all ages up to 14 and 11, respectively.
After taking the differences in socioeconomic position and maternal cognitive ability into account, those children who were breastfed for longer scored higher in cognitive measures up to age 14, compared with children who were not breastfed. They also found that longer breastfeeding durations were associated with mean cognitive scores 0.08-0.26 standard deviations higher than the mean cognitive score of those who were never breastfed. “This difference may seem small for an individual child but could be important at the population level,” the authors commented.
Modest effect
In the United Kingdom, women who have more educational qualifications and are more economically advantaged tend to breastfeed for longer, said the authors. In addition, they added, this group tends to “score more highly on cognitive tests.”
These differences could explain why babies who breastfeed for longer do better in cognitive assessments. However, they said that in their study, “we found that even after taking these differences into account, children breastfed for longer scored higher in cognitive measures up to age 14, in comparison to children who were not breastfed.”
The authors explained that the association between breastfeeding duration and cognitive scores “persists after adjusting for socioeconomics and maternal intelligence.” However, they pointed out that “the effect was modest.”
A version of this article first appeared on Medscape UK.
Breastfeeding duration is associated with improved cognitive scores at ages 5-14, even after controlling for maternal socioeconomic position and cognitive ability, said the researchers behind a new study.
Despite previous studies demonstrating an association between breastfeeding and standardized intelligence test scores – with breastfed infants scoring higher on intelligence tests than non-breastfed infants – a causal relationship is still contested.
“There is some debate about whether breastfeeding a baby for a longer period of time improves their cognitive development,” the authors of the new study said. They went on to explain how improved cognitive outcomes in breastfed infants could potentially be explained by other characteristics of the women, such as “socioeconomics and maternal intelligence.”
Important at the population level
For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford (England) set out to investigate how much these confounders influenced the association between breastfeeding duration and cognitive development.
They analyzed data from the U.K. Millennium Cohort Study on 7,855 infants born in 2000 to 2002 and followed until age 14. They highlighted that although the cohort was not specifically designed to address the association between breastfeeding and cognition, it included information on duration of any breastfeeding, duration of exclusive breastfeeding, verbal cognitive scores at ages 5, 7, 11, and 14, spatial cognitive scores at ages 5, 7, and 11, as well as potential confounders, including socioeconomic characteristics and maternal cognition, based on a vocabulary test.
The researchers discovered that longer breastfeeding durations were associated with higher verbal and spatial cognitive scores at all ages up to 14 and 11, respectively.
After taking the differences in socioeconomic position and maternal cognitive ability into account, those children who were breastfed for longer scored higher in cognitive measures up to age 14, compared with children who were not breastfed. They also found that longer breastfeeding durations were associated with mean cognitive scores 0.08-0.26 standard deviations higher than the mean cognitive score of those who were never breastfed. “This difference may seem small for an individual child but could be important at the population level,” the authors commented.
Modest effect
In the United Kingdom, women who have more educational qualifications and are more economically advantaged tend to breastfeed for longer, said the authors. In addition, they added, this group tends to “score more highly on cognitive tests.”
These differences could explain why babies who breastfeed for longer do better in cognitive assessments. However, they said that in their study, “we found that even after taking these differences into account, children breastfed for longer scored higher in cognitive measures up to age 14, in comparison to children who were not breastfed.”
The authors explained that the association between breastfeeding duration and cognitive scores “persists after adjusting for socioeconomics and maternal intelligence.” However, they pointed out that “the effect was modest.”
A version of this article first appeared on Medscape UK.
FROM PLOS ONE
Thrombolysis is safe in stroke patients on oral anticoagulants
, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.
Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.
“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.
“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”
The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
A ‘daily clinical problem’
As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.
A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.
“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”
Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.
Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.
Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.
Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).
There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).
This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.
“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
Infrastructure needed
While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.
“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”
Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.
“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”
Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”
But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.
In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.
“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”
The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.
Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.
“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.
“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”
The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
A ‘daily clinical problem’
As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.
A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.
“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”
Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.
Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.
Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.
Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).
There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).
This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.
“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
Infrastructure needed
While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.
“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”
Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.
“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”
Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”
But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.
In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.
“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”
The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.
Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.
“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.
“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”
The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
A ‘daily clinical problem’
As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.
A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.
“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”
Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.
Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.
Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.
Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).
There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).
This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.
“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
Infrastructure needed
While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.
“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”
Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.
“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”
Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”
But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.
In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.
“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”
The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ESOC 2022
New insight into how brain stimulation eases major depression
For the first time, researchers understand what happens to the brain when patients with treatment-resistant depression receive repetitive transcranial magnetic stimulation (rTMS).
Using functional magnetic resonance imaging (fMRI), they showed that rTMS induces widespread alterations in functional connectivity in brain regions involved in emotion and motor control.
“‘How does rTMS work?’ is one of the most frequent questions I get in clinic. Providing an accurate explanation and narrative to patients is critical,” senior investigator Fidel Vila-Rodriguez, MD, PhD, director of the Non-Invasive Neurostimulation Therapies Laboratory, University of British Columbia, Vancouver, told this news organization.
“Our findings suggest that rTMS might rely on the brain’s capacity for change (neuroplasticity) to exert its effects and that rTMS effects on the brain are widespread beyond the focal area stimulated (functional network effects),” Dr. Vila-Rodriguez added.
The study was published online in the American Journal of Psychiatry.
Mechanistic insights
Although rTMS has proven efficacy for treatment-resistant depression, the mechanisms behind how it affects the brain are not well understood.
In the current study, researchers used fMRI to assess changes in functional connectivity induced by a single rTMS session in 26 women and 12 men with treatment-resistant depression.
They found that – from managing emotional responses to memory and motor control.
Following a 4-week course of rTMS, these connectivity changes predicted about 30% of the variance of improvement in scores on the Montgomery-Åsberg Depression Rating Scale after rTMS treatment.
The most robust predictive associations involved connections between prefrontal regions and motor, parietal, and insular cortices and between bilateral regions of the thalamus.
“By demonstrating this principle and identifying regions of the brain that are activated by rTMS, we can now try to understand whether this pattern can be used as a biomarker,” Dr. Vila-Rodriguez said in a news release.
“This work provides a mechanistic explanation of what rTMS does to treat depression and supports the notion that for rTMS to treat depressive symptoms a distributed change in brain activity (network or circuit base) is necessary,” he told this news organization.
With funding from the Canadian Institutes of Health Research (CIHR), the team will next see if they can use fMRI to guide rTMS at the individual level, with the ultimate goal of “personalizing” rTMS using individualized functional targets, Dr. Vila-Rodriguez said.
New generation of tms researchers
Reached for comment, Jonathan Downar, MD, PhD, department of psychiatry, University of Toronto, noted that TMS can be “very effective” for treatment-resistant depression, and it has a “very clean side effect profile compared to medications.”
What the field is trying to figure out now is “who it works for and how we can predict more effectively who’s going to benefit from it,” Dr. Downar said in an interview.
He noted that the study’s investigators are part of a “new generation of TMS researchers who are bringing new ideas into the fold and figuring out how to use brain imaging to personalize the treatment.” This study represents “a step” in that direction.
“A challenge for the field is that it’s often pretty easy to demonstrate a change at the group level, but the question is whether we can use that at the individual level. That’s a higher bar to meet, and we’re still not there yet,” Dr. Downar added.
Support for the study was provided by Brain Canada, the Michael Smith Foundation for Health Research and the Vancouver Coastal Health Research Institute. Dr. Vila-Rodriguez has received research support from CIHR, Brain Canada, the Michael Smith Foundation for Health Research, the Vancouver Coastal Health Research Institute, and the Weston Brain Institute for investigator-initiated research and philanthropic support from the Seedlings Foundation; he received in-kind equipment support from MagVenture for this investigator-initiated trial; and he has received honoraria for participation on an advisory board for Janssen. Dr. Downar has served as an adviser for BrainCheck, NeuroStim TMS, and Salience Neuro Health; received research grant from CIHR, National Institute for Mental Health, Brain Canada, Canadian Biomarker Integration Network in Depression, Ontario Brain Institute, Klarman Family Foundation, Arrell Family Foundation and the Edgestone Foundation; received travel stipends from Lundbeck and ANT Neuro; and received in-kind equipment support for investigator-initiated trials from MagVenture.
A version of this article first appeared on Medscape.com.
For the first time, researchers understand what happens to the brain when patients with treatment-resistant depression receive repetitive transcranial magnetic stimulation (rTMS).
Using functional magnetic resonance imaging (fMRI), they showed that rTMS induces widespread alterations in functional connectivity in brain regions involved in emotion and motor control.
“‘How does rTMS work?’ is one of the most frequent questions I get in clinic. Providing an accurate explanation and narrative to patients is critical,” senior investigator Fidel Vila-Rodriguez, MD, PhD, director of the Non-Invasive Neurostimulation Therapies Laboratory, University of British Columbia, Vancouver, told this news organization.
“Our findings suggest that rTMS might rely on the brain’s capacity for change (neuroplasticity) to exert its effects and that rTMS effects on the brain are widespread beyond the focal area stimulated (functional network effects),” Dr. Vila-Rodriguez added.
The study was published online in the American Journal of Psychiatry.
Mechanistic insights
Although rTMS has proven efficacy for treatment-resistant depression, the mechanisms behind how it affects the brain are not well understood.
In the current study, researchers used fMRI to assess changes in functional connectivity induced by a single rTMS session in 26 women and 12 men with treatment-resistant depression.
They found that – from managing emotional responses to memory and motor control.
Following a 4-week course of rTMS, these connectivity changes predicted about 30% of the variance of improvement in scores on the Montgomery-Åsberg Depression Rating Scale after rTMS treatment.
The most robust predictive associations involved connections between prefrontal regions and motor, parietal, and insular cortices and between bilateral regions of the thalamus.
“By demonstrating this principle and identifying regions of the brain that are activated by rTMS, we can now try to understand whether this pattern can be used as a biomarker,” Dr. Vila-Rodriguez said in a news release.
“This work provides a mechanistic explanation of what rTMS does to treat depression and supports the notion that for rTMS to treat depressive symptoms a distributed change in brain activity (network or circuit base) is necessary,” he told this news organization.
With funding from the Canadian Institutes of Health Research (CIHR), the team will next see if they can use fMRI to guide rTMS at the individual level, with the ultimate goal of “personalizing” rTMS using individualized functional targets, Dr. Vila-Rodriguez said.
New generation of tms researchers
Reached for comment, Jonathan Downar, MD, PhD, department of psychiatry, University of Toronto, noted that TMS can be “very effective” for treatment-resistant depression, and it has a “very clean side effect profile compared to medications.”
What the field is trying to figure out now is “who it works for and how we can predict more effectively who’s going to benefit from it,” Dr. Downar said in an interview.
He noted that the study’s investigators are part of a “new generation of TMS researchers who are bringing new ideas into the fold and figuring out how to use brain imaging to personalize the treatment.” This study represents “a step” in that direction.
“A challenge for the field is that it’s often pretty easy to demonstrate a change at the group level, but the question is whether we can use that at the individual level. That’s a higher bar to meet, and we’re still not there yet,” Dr. Downar added.
Support for the study was provided by Brain Canada, the Michael Smith Foundation for Health Research and the Vancouver Coastal Health Research Institute. Dr. Vila-Rodriguez has received research support from CIHR, Brain Canada, the Michael Smith Foundation for Health Research, the Vancouver Coastal Health Research Institute, and the Weston Brain Institute for investigator-initiated research and philanthropic support from the Seedlings Foundation; he received in-kind equipment support from MagVenture for this investigator-initiated trial; and he has received honoraria for participation on an advisory board for Janssen. Dr. Downar has served as an adviser for BrainCheck, NeuroStim TMS, and Salience Neuro Health; received research grant from CIHR, National Institute for Mental Health, Brain Canada, Canadian Biomarker Integration Network in Depression, Ontario Brain Institute, Klarman Family Foundation, Arrell Family Foundation and the Edgestone Foundation; received travel stipends from Lundbeck and ANT Neuro; and received in-kind equipment support for investigator-initiated trials from MagVenture.
A version of this article first appeared on Medscape.com.
For the first time, researchers understand what happens to the brain when patients with treatment-resistant depression receive repetitive transcranial magnetic stimulation (rTMS).
Using functional magnetic resonance imaging (fMRI), they showed that rTMS induces widespread alterations in functional connectivity in brain regions involved in emotion and motor control.
“‘How does rTMS work?’ is one of the most frequent questions I get in clinic. Providing an accurate explanation and narrative to patients is critical,” senior investigator Fidel Vila-Rodriguez, MD, PhD, director of the Non-Invasive Neurostimulation Therapies Laboratory, University of British Columbia, Vancouver, told this news organization.
“Our findings suggest that rTMS might rely on the brain’s capacity for change (neuroplasticity) to exert its effects and that rTMS effects on the brain are widespread beyond the focal area stimulated (functional network effects),” Dr. Vila-Rodriguez added.
The study was published online in the American Journal of Psychiatry.
Mechanistic insights
Although rTMS has proven efficacy for treatment-resistant depression, the mechanisms behind how it affects the brain are not well understood.
In the current study, researchers used fMRI to assess changes in functional connectivity induced by a single rTMS session in 26 women and 12 men with treatment-resistant depression.
They found that – from managing emotional responses to memory and motor control.
Following a 4-week course of rTMS, these connectivity changes predicted about 30% of the variance of improvement in scores on the Montgomery-Åsberg Depression Rating Scale after rTMS treatment.
The most robust predictive associations involved connections between prefrontal regions and motor, parietal, and insular cortices and between bilateral regions of the thalamus.
“By demonstrating this principle and identifying regions of the brain that are activated by rTMS, we can now try to understand whether this pattern can be used as a biomarker,” Dr. Vila-Rodriguez said in a news release.
“This work provides a mechanistic explanation of what rTMS does to treat depression and supports the notion that for rTMS to treat depressive symptoms a distributed change in brain activity (network or circuit base) is necessary,” he told this news organization.
With funding from the Canadian Institutes of Health Research (CIHR), the team will next see if they can use fMRI to guide rTMS at the individual level, with the ultimate goal of “personalizing” rTMS using individualized functional targets, Dr. Vila-Rodriguez said.
New generation of tms researchers
Reached for comment, Jonathan Downar, MD, PhD, department of psychiatry, University of Toronto, noted that TMS can be “very effective” for treatment-resistant depression, and it has a “very clean side effect profile compared to medications.”
What the field is trying to figure out now is “who it works for and how we can predict more effectively who’s going to benefit from it,” Dr. Downar said in an interview.
He noted that the study’s investigators are part of a “new generation of TMS researchers who are bringing new ideas into the fold and figuring out how to use brain imaging to personalize the treatment.” This study represents “a step” in that direction.
“A challenge for the field is that it’s often pretty easy to demonstrate a change at the group level, but the question is whether we can use that at the individual level. That’s a higher bar to meet, and we’re still not there yet,” Dr. Downar added.
Support for the study was provided by Brain Canada, the Michael Smith Foundation for Health Research and the Vancouver Coastal Health Research Institute. Dr. Vila-Rodriguez has received research support from CIHR, Brain Canada, the Michael Smith Foundation for Health Research, the Vancouver Coastal Health Research Institute, and the Weston Brain Institute for investigator-initiated research and philanthropic support from the Seedlings Foundation; he received in-kind equipment support from MagVenture for this investigator-initiated trial; and he has received honoraria for participation on an advisory board for Janssen. Dr. Downar has served as an adviser for BrainCheck, NeuroStim TMS, and Salience Neuro Health; received research grant from CIHR, National Institute for Mental Health, Brain Canada, Canadian Biomarker Integration Network in Depression, Ontario Brain Institute, Klarman Family Foundation, Arrell Family Foundation and the Edgestone Foundation; received travel stipends from Lundbeck and ANT Neuro; and received in-kind equipment support for investigator-initiated trials from MagVenture.
A version of this article first appeared on Medscape.com.
Many Americans missing an opportunity to prevent dementia
(ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.
Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.
In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.
The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
A missed prevention opportunity
More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD.
The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.
Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)
The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.
In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.
The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.
In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.
“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.
“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.
A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.
A version of this article first appeared on Medscape.com.
(ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.
Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.
In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.
The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
A missed prevention opportunity
More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD.
The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.
Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)
The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.
In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.
The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.
In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.
“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.
“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.
A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.
A version of this article first appeared on Medscape.com.
(ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.
Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.
In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.
The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
A missed prevention opportunity
More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD.
The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.
Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)
The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.
In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.
The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.
In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.
“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.
“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.
A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.
A version of this article first appeared on Medscape.com.
FROM MMWR
SCAI issues guidelines for PFO management, makes case for expansion
The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.
“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.
The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.
The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.
The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.
“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”
The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”
Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:
- Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
- Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.
In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.
“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.
The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.
The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”
The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.
In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.
“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.
Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.
The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.
“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.
The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.
The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.
The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.
“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”
The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”
Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:
- Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
- Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.
In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.
“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.
The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.
The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”
The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.
In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.
“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.
Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.
The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.
“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.
The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.
The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.
The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.
“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”
The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”
Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:
- Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
- Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.
In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.
“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.
The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.
The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”
The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.
In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.
“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.
Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.
FROM SCAI 2022
Advances In Neurologic Care
- Pharmacist Impact on Access to Care in an Epilepsy Clinic
- MRI Protocols for Veterans With Multiple Sclerosis
- Neuroimaging in the Era of Artificial Intelligence
- Autonomic Dysfunction in CADASIL Syndrome
- Pharmacist Impact on Access to Care in an Epilepsy Clinic
- MRI Protocols for Veterans With Multiple Sclerosis
- Neuroimaging in the Era of Artificial Intelligence
- Autonomic Dysfunction in CADASIL Syndrome
- Pharmacist Impact on Access to Care in an Epilepsy Clinic
- MRI Protocols for Veterans With Multiple Sclerosis
- Neuroimaging in the Era of Artificial Intelligence
- Autonomic Dysfunction in CADASIL Syndrome
Updated AHA/ASA guideline changes care for spontaneous intracerebral hemorrhage
Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).
Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.
The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.
“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.
“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.
“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.
Time-honored treatments no more?
Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.
For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.
Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.
“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.
The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.
In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.
The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.
For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.
It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.
For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.
However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
Multidisciplinary care
For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.
Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.
Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.
“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.
The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
Opportunity for prevention?
The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.
While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.
“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.
“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.
“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.
The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.
This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.
A version of this article first appeared on Medscape.com.
Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).
Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.
The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.
“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.
“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.
“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.
Time-honored treatments no more?
Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.
For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.
Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.
“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.
The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.
In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.
The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.
For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.
It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.
For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.
However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
Multidisciplinary care
For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.
Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.
Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.
“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.
The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
Opportunity for prevention?
The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.
While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.
“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.
“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.
“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.
The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.
This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.
A version of this article first appeared on Medscape.com.
Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).
Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.
The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.
“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.
“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.
“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.
Time-honored treatments no more?
Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.
For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.
Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.
“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.
The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.
In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.
The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.
For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.
It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.
For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.
However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
Multidisciplinary care
For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.
Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.
Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.
“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.
The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
Opportunity for prevention?
The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.
While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.
“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.
“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.
“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.
The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.
This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.
A version of this article first appeared on Medscape.com.
The psychopathic brain: New insight
Using MRI, researchers found that the striatum was about 10% larger on average in adults with psychopathic traits than in matched control persons and that this relationship was mediated by stimulation seeking and impulsivity.
The striatum is a subcortical region of the forebrain involved in the cognitive processing of reward-related information and motivational aspects of behavior.
“Our study’s results help advance our knowledge about what underlies antisocial behavior such as psychopathy,” co-author and neurocriminologist Olivia Choy, PhD, with Nanyang Technological University, Singapore, said in a news release.
“In addition to social environmental influences, it is important to consider that there can be differences in biology – in this case, the size of brain structures – between antisocial and non-antisocial individuals,” Dr. Choy added.
The study was published online in the Journal of Psychiatric Research.
Antisocial, egocentric
Individuals with psychopathic traits typically have an egocentric and antisocial personality. They generally lack remorse for their actions or empathy for others and often have criminal tendencies.
Some prior research suggests links between psychopathy and an overactive striatum, but it was unclear what role striatal volume plays in this behavior.
For the study, investigators assessed striatal volume using MRI in 120 adults living in the community, and they assessed psychopathy using the Psychopathy Checklist – Revised.
Correlational analyses showed that increased striatal volumes were associated with more psychopathic traits (P = .001) in both men and women.
Volumetric increases were found for all subregions of the striatum in psychopathic individuals, after controlling for age, substance dependence, substance abuse, antisocial personality disorder, attention-deficit/hyperactivity disorder, social adversity, and total brain volume.
An analysis of 18 psychopathic individuals showed that striatal volumes were increased 9.4%, compared with 18 propensity-matched control persons (P = .01).
Abnormal reward processing
Stimulation seeking and impulsivity partly mediated the striatal-psychopathy relationship, accounting for 49.4% of this association.
These findings “replicate and build on initial studies indicating striatal enlargement in adults with psychopathy, yielding an updated effect size of d = 0.48,” the researchers note.
The results are “consistent with the notion that striatal abnormalities in individuals with psychopathy partly reflect increased sensation-seeking and impulsivity and support the hypothesis of abnormal reward processing in psychopathy,” they add.
“We have always known that psychopaths go to extreme lengths to seek out rewards, including criminal activities that involve property, sex, and drugs,” co-author Adrian Raine, DPhil, department of criminology, psychiatry, and psychology, University of Pennsylvania, Philadelphia, said in a news release.
“We are now finding out a neurobiological underpinning of this impulsive and stimulating behavior in the form of enlargement to the striatum, a key brain area involved in rewards,” Dr. Raine added.
What causes striatal enlargement in individuals with psychopathy still needs to be determined.
In human development, the striatum typically becomes smaller as a child matures, suggesting that psychopathy is associated with differences in brain development, the researchers suggest.
“Because biological traits, such as the size of one’s striatum, can be inherited to child from parent, these findings give added support to neurodevelopmental perspectives of psychopathy – that the brains of these offenders do not develop normally throughout childhood and adolescence,” said Dr. Raine.
Larger studies needed
Commenting on the findings for this news organization, Terrie E. Moffitt, PhD, professor of psychology, Duke University, Durham, N.C., noted that there is “general consensus among brain-imaging researchers that testing brain-behavior relations requires very large samples in the thousands and also samples of research participants who represent the full extent of variation in the population as well as possible – from rich to poor, from well to unwell, from high IQ to low IQ, from strong mental health to mental illness, etc.
“It would be grand to see this study’s provocative finding replicated in a large, representative sampling design,” Dr. Moffitt said.
The study was supported in part by the National Institutes of Health. Dr. Choy, Dr. Raine, and Dr. Moffitt have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Using MRI, researchers found that the striatum was about 10% larger on average in adults with psychopathic traits than in matched control persons and that this relationship was mediated by stimulation seeking and impulsivity.
The striatum is a subcortical region of the forebrain involved in the cognitive processing of reward-related information and motivational aspects of behavior.
“Our study’s results help advance our knowledge about what underlies antisocial behavior such as psychopathy,” co-author and neurocriminologist Olivia Choy, PhD, with Nanyang Technological University, Singapore, said in a news release.
“In addition to social environmental influences, it is important to consider that there can be differences in biology – in this case, the size of brain structures – between antisocial and non-antisocial individuals,” Dr. Choy added.
The study was published online in the Journal of Psychiatric Research.
Antisocial, egocentric
Individuals with psychopathic traits typically have an egocentric and antisocial personality. They generally lack remorse for their actions or empathy for others and often have criminal tendencies.
Some prior research suggests links between psychopathy and an overactive striatum, but it was unclear what role striatal volume plays in this behavior.
For the study, investigators assessed striatal volume using MRI in 120 adults living in the community, and they assessed psychopathy using the Psychopathy Checklist – Revised.
Correlational analyses showed that increased striatal volumes were associated with more psychopathic traits (P = .001) in both men and women.
Volumetric increases were found for all subregions of the striatum in psychopathic individuals, after controlling for age, substance dependence, substance abuse, antisocial personality disorder, attention-deficit/hyperactivity disorder, social adversity, and total brain volume.
An analysis of 18 psychopathic individuals showed that striatal volumes were increased 9.4%, compared with 18 propensity-matched control persons (P = .01).
Abnormal reward processing
Stimulation seeking and impulsivity partly mediated the striatal-psychopathy relationship, accounting for 49.4% of this association.
These findings “replicate and build on initial studies indicating striatal enlargement in adults with psychopathy, yielding an updated effect size of d = 0.48,” the researchers note.
The results are “consistent with the notion that striatal abnormalities in individuals with psychopathy partly reflect increased sensation-seeking and impulsivity and support the hypothesis of abnormal reward processing in psychopathy,” they add.
“We have always known that psychopaths go to extreme lengths to seek out rewards, including criminal activities that involve property, sex, and drugs,” co-author Adrian Raine, DPhil, department of criminology, psychiatry, and psychology, University of Pennsylvania, Philadelphia, said in a news release.
“We are now finding out a neurobiological underpinning of this impulsive and stimulating behavior in the form of enlargement to the striatum, a key brain area involved in rewards,” Dr. Raine added.
What causes striatal enlargement in individuals with psychopathy still needs to be determined.
In human development, the striatum typically becomes smaller as a child matures, suggesting that psychopathy is associated with differences in brain development, the researchers suggest.
“Because biological traits, such as the size of one’s striatum, can be inherited to child from parent, these findings give added support to neurodevelopmental perspectives of psychopathy – that the brains of these offenders do not develop normally throughout childhood and adolescence,” said Dr. Raine.
Larger studies needed
Commenting on the findings for this news organization, Terrie E. Moffitt, PhD, professor of psychology, Duke University, Durham, N.C., noted that there is “general consensus among brain-imaging researchers that testing brain-behavior relations requires very large samples in the thousands and also samples of research participants who represent the full extent of variation in the population as well as possible – from rich to poor, from well to unwell, from high IQ to low IQ, from strong mental health to mental illness, etc.
“It would be grand to see this study’s provocative finding replicated in a large, representative sampling design,” Dr. Moffitt said.
The study was supported in part by the National Institutes of Health. Dr. Choy, Dr. Raine, and Dr. Moffitt have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Using MRI, researchers found that the striatum was about 10% larger on average in adults with psychopathic traits than in matched control persons and that this relationship was mediated by stimulation seeking and impulsivity.
The striatum is a subcortical region of the forebrain involved in the cognitive processing of reward-related information and motivational aspects of behavior.
“Our study’s results help advance our knowledge about what underlies antisocial behavior such as psychopathy,” co-author and neurocriminologist Olivia Choy, PhD, with Nanyang Technological University, Singapore, said in a news release.
“In addition to social environmental influences, it is important to consider that there can be differences in biology – in this case, the size of brain structures – between antisocial and non-antisocial individuals,” Dr. Choy added.
The study was published online in the Journal of Psychiatric Research.
Antisocial, egocentric
Individuals with psychopathic traits typically have an egocentric and antisocial personality. They generally lack remorse for their actions or empathy for others and often have criminal tendencies.
Some prior research suggests links between psychopathy and an overactive striatum, but it was unclear what role striatal volume plays in this behavior.
For the study, investigators assessed striatal volume using MRI in 120 adults living in the community, and they assessed psychopathy using the Psychopathy Checklist – Revised.
Correlational analyses showed that increased striatal volumes were associated with more psychopathic traits (P = .001) in both men and women.
Volumetric increases were found for all subregions of the striatum in psychopathic individuals, after controlling for age, substance dependence, substance abuse, antisocial personality disorder, attention-deficit/hyperactivity disorder, social adversity, and total brain volume.
An analysis of 18 psychopathic individuals showed that striatal volumes were increased 9.4%, compared with 18 propensity-matched control persons (P = .01).
Abnormal reward processing
Stimulation seeking and impulsivity partly mediated the striatal-psychopathy relationship, accounting for 49.4% of this association.
These findings “replicate and build on initial studies indicating striatal enlargement in adults with psychopathy, yielding an updated effect size of d = 0.48,” the researchers note.
The results are “consistent with the notion that striatal abnormalities in individuals with psychopathy partly reflect increased sensation-seeking and impulsivity and support the hypothesis of abnormal reward processing in psychopathy,” they add.
“We have always known that psychopaths go to extreme lengths to seek out rewards, including criminal activities that involve property, sex, and drugs,” co-author Adrian Raine, DPhil, department of criminology, psychiatry, and psychology, University of Pennsylvania, Philadelphia, said in a news release.
“We are now finding out a neurobiological underpinning of this impulsive and stimulating behavior in the form of enlargement to the striatum, a key brain area involved in rewards,” Dr. Raine added.
What causes striatal enlargement in individuals with psychopathy still needs to be determined.
In human development, the striatum typically becomes smaller as a child matures, suggesting that psychopathy is associated with differences in brain development, the researchers suggest.
“Because biological traits, such as the size of one’s striatum, can be inherited to child from parent, these findings give added support to neurodevelopmental perspectives of psychopathy – that the brains of these offenders do not develop normally throughout childhood and adolescence,” said Dr. Raine.
Larger studies needed
Commenting on the findings for this news organization, Terrie E. Moffitt, PhD, professor of psychology, Duke University, Durham, N.C., noted that there is “general consensus among brain-imaging researchers that testing brain-behavior relations requires very large samples in the thousands and also samples of research participants who represent the full extent of variation in the population as well as possible – from rich to poor, from well to unwell, from high IQ to low IQ, from strong mental health to mental illness, etc.
“It would be grand to see this study’s provocative finding replicated in a large, representative sampling design,” Dr. Moffitt said.
The study was supported in part by the National Institutes of Health. Dr. Choy, Dr. Raine, and Dr. Moffitt have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.