Neurology

Neurologic disorders are major causes of death and disability. Globally, the burden of neurologic disorders continues to increase. The prevalence of disabling neurologic disorders significantly increases with age. As people live longer, health care systems will face increasing demands for treatment, rehabilitation, and support services for neurologic disorders. The scarcity of established modifiable risks for most of the neurologic burden demonstrates how new knowledge is required to develop effective prevention and treatment strategies.¹

A single-center study for chronic headache at a rural institution found that, when combined with public education, clinician education not only can increase access to care but also reduce specialist overuse, hospitalizations, polypharmacy, and emergency department visits.² A predicted shortage of neurologists has sparked increased interest in the field and individual neurology educators are helping fuel its popularity.^3-5

TELE-EDUCATION

Educating the next generation of health professionals is 1 of 4 statutory missions of the US Department of Veterans Affairs (VA).⁶ Tele-education (also known as telelearning and distance learning) deviates from traditional in-person classroom settings, in which the lecture has been a core pedagogic method.⁷ Audio, video, and online technologies provide health education and can overcome geographic barriers for rural and remote clinicians.⁸ Recent technological improvements have allowed for inexpensive and efficient dissemination of educational materials, including video lectures, podcasts, online modules, assessment materials, and even entire curricula.⁹

There has been an increase in the awareness of the parallel curriculum involving self-directed and asynchronous learning opportunities. ¹⁰ Several studies report knowledge gained via tele-education is comparable to conventional classroom learning.^11-13 A systematic review of e-learning perceptions among health care students suggested benefits (eg, learning flexibility, pedagogical design, online interactions, basic computer skills, and access to technology) and drawbacks (eg, limited acquisition of clinical skills, internet connection problems, and issues with using educational platforms).¹

The COVID-19 pandemic forced an abrupt cessation of traditional in-person education, forcing educational institutions and medical organizations to transition to telelearning. Solutions in the education field appeared during the pandemic, such as videoconferencing, social media, and telemedicine, that effectively addressed the sudden cessation of in-person medical education.¹⁵

Graduate medical education in neurology residency programs served as an experimental set up for tele-education during the pandemic. Residents from neurology training programs outlined the benefits of a volunteer lecturer-based online didactic program that was established to meet this need, which included exposure to subspeciality topics, access to subspecialist experts not available within the department, exposure to different pedagogic methods, interaction with members of other educational institutions and training programs, career development opportunities, and the potential for forming a community of learning.¹⁶

Not all recent educational developments are technology-based. For example, instruction focused on specific patient experiences, and learning processes that emphasize problem solving and personal responsibility over specific knowledge have been successful in neurology.^17,18 Departments and institutions must be creative in finding ways to fund continuing education, especially when budgets are limited.¹⁹

ANNUAL NEUROLOGY SEMINAR

An annual Veterans Health Administration (VHA) neurology seminar began in 2019 as a 1-day in-person event. Neurologists at the Michael E. DeBakey VA Medical Center in Houston presented in 50-minute sessions. Nonspecialist clinical personnel and neurology clinicians attended the event. Attendees requested making the presentations widely available and regularly repeating the seminar.

The second neurology seminar took place during the COVID-19 pandemic. It was conducted online and advertised across the Veterans Integrated Services Network (VISN) 16. The 1-day program had 204 participants who were primarily nurses (59%) and physicians (21%); 94% agreed with the program objectives (Table 1). Participants could earn CME credits for the 7 presentations primarily by VHA experts.

Based on feedback and a needs assessment, the program expanded in 2021 and 2022. With support from the national VHA neurology office and VHA Employee Education System (EES), the Institute for Learning, Education, and Development (ILEAD), the feedback identified topics that resonate with VHA clinicians. Neurological disorders in the fields of stroke, dementia, and headache were included since veterans with these disorders regularly visit primary care, geriatrics, mental health, and other clinical offices. Updates provided in the diagnosis and treatment of common neurological disorders were well received. Almost all speakers were VHA clinicians, which allowed them to focus on topics relevant to clinical practice at the VHA.

Attendance has increased annually. In 2021, 550 clinicians registered (52% nurses) and 433 completed the postseminar survey (Table 2). In 2022, 635 participants registered and 342 completed evaluations, including attendees from other federal agencies who were invited to participate via EES TRAIN (Training Finder Real-time Affiliate Integrated Network). Forty-seven participants from other federal agencies, including the US Department of Defense, National Institute of Health, and Centers for Disease Control and Prevention, completed the feedback evaluation via TRAIN (Table 3). Participants report high levels of satisfaction each year (mean of 4.5 on a 5-point scale). Respondents preferred conventional lecture presentation and case-based discussions for the teaching format and dementia was the most requested topic for future seminars (Table 4).

The content of each seminar was designed to include . 1 topic relevant to current clinical practice. The 2020 seminar covered topics of cerebrovascular complications of COVID- 19 and living well with neurodegenerative disease in the COVID-19 era. In 2021, the seminar included COVID-19 and neurologic manifestations. In 2022, topics included trends in stroke rehabilitation. In addition, ≥ 1 session addressed neurologic issues within the VHA. In 2020, the VA Deputy National Director of Neurology presented on the VHA stroke systems of care. In 2021, there was a presentation on traumatic brain injury (TBI) in the military. In 2022, sessions covered long term neurologic consequences of TBI and use of telemedicine for neurologic disorders. Feedback on the sessions were positive (eAppendix, available at doi:10.12788/fp.0545).

At the request of the participants, individual presentations were shared via email by the course director and speakers. In collaboration with the EES, each session was recorded and the 2022 seminar was made available to registrants in TMS and EES TRAIN and via the VHA Neurology SharePoint.

DISCUSSION

The annual VHA neurology seminar is a 1-day neurology conference that provides education to general neurologists and other clinicians caring for patients with neurologic disorders. It is the first of its kind neurology education program in the VHA covering most subspecialties in neurology and aims at improving neurologic patient care and access through education. Sessions have covered stroke, epilepsy, sleep, amyotrophic lateral sclerosis, neuropathy, dementia, movement disorders and Parkinson disease, headaches, multiple sclerosis, neurorehabilitation, and telehealth.

The seminar has transitioned from an inperson meeting to a virtual format, making neurology education more convenient and accessible. The virtual format provides the means to increase educational collaborations and share lecture platforms with other federal agencies. The program offers CME credits at no cost to government employees. Recorded lectures can also be asynchronously viewed from the Neurology SharePoint without the ability to earn CME credits. These recordings may be used to educate trainees as well.

The seminar aims to educate all health care professionals caring for patients with neurologic disorders. It aims to eliminate neurophobia, the fear of neural sciences and clinical neurology, and help general practitioners, especially in rural areas, take care of patients with neurologic disorders. The seminars introduce general practitioners to VHA neurology experts; the epilepsy, headache multiple sclerosis, and Parkinson disease centers of excellence; and the national programs for telestroke and teleneurology.

Education Support in the VHA

The EES/ILEAD provides a wide variety of learning opportunities to VHA employees on a broad range of topics, making it one of the largest medical education programs in the country. Pharmacists, social workers, psychologists, therapists, nurses, physician assistants, and physicians have access to certified training opportunities to gain knowledge and skills needed to provide high-quality, veteran-centered care.

A review of geriatrics learning activities through the EES found > 15,000 lectures from 1999 to 2009 for > 300,000 attendees.²⁰ To our knowledge, a review of neurology-related learning activities offered by the EES/ILEAD has not been completed, but the study on geriatrics shows that a similar review would be feasible, given the integrated education system, and helpful in identifying what topics are covered, formats are used, and participants are engaged in neurology education at the VHA. This is a future project planned by the neurology education workgroup.

The EES/ILEAD arranged CME credit for the VHA Neurology Seminar and assisted in organizing an online event with > 500 attendees. Technology support and tools provided by EES during the virtual seminar, such as polling and chat features, kept the audience engaged. Other specialties may similarly value a virtual, all-day seminar format that is efficient and can encourage increased participation from practitioners, nurses, and clinicians.

Future Growth

We plan to increase future participation in the annual neurology seminar with primary care, geriatrics, neurology, and other specialties by instituting an improved and earlier marketing strategy. This includes working with the VHA neurology office to inform neurology practitioners as well as other program offices in the VHA. We intend to host the seminar the same day every year to make it easy for attendees to plan accordingly. In the future we may consider hybrid in-person and virtual modalities if feasible. We plan to focus on reaching out to other government agencies through platforms like TRAIN and the American Academy of Neurology government sections. Securing funding, administrative staff, and protected time in the future may help expand the program further.

Limitations

While a virtual format offers several advantages, using it removes the feel of an in-person meeting, which could be viewed by some attendees as a limitation. The other challenges and drawbacks of transitioning to the virtual platform for a national meeting are similar to those reported in the literature: time zone differences, internet issues, and participants having difficulty using certain online platforms. Attendance could also be limited by scheduling conflicts.¹⁶ Despite a large audience attending the seminar, many clinicians do not get protected time from their institutions. Institutional and leadership support at national and local levels will likely improve participation and help participants earn CME credits. While we are still doing a preliminary needs assessment, a formal needs assessment across federal governmental organizations will be helpful.

CONCLUSIONS

The annual VHA neurology seminar promotes interprofessional education, introduces neurology subspecialty centers of excellence, improves access to renowned neurology experts, and provides neurology-related updates through a VHA lens. The program not only provides educational updates to neurology clinicians, but also increases the confidence of non-neurology clinicians called to care for veterans with neurological disorders in their respective clinics.

Neurologic disorders are major causes of death and disability. Globally, the burden of neurologic disorders continues to increase. The prevalence of disabling neurologic disorders significantly increases with age. As people live longer, health care systems will face increasing demands for treatment, rehabilitation, and support services for neurologic disorders. The scarcity of established modifiable risks for most of the neurologic burden demonstrates how new knowledge is required to develop effective prevention and treatment strategies.¹

A single-center study for chronic headache at a rural institution found that, when combined with public education, clinician education not only can increase access to care but also reduce specialist overuse, hospitalizations, polypharmacy, and emergency department visits.² A predicted shortage of neurologists has sparked increased interest in the field and individual neurology educators are helping fuel its popularity.^3-5

TELE-EDUCATION

Educating the next generation of health professionals is 1 of 4 statutory missions of the US Department of Veterans Affairs (VA).⁶ Tele-education (also known as telelearning and distance learning) deviates from traditional in-person classroom settings, in which the lecture has been a core pedagogic method.⁷ Audio, video, and online technologies provide health education and can overcome geographic barriers for rural and remote clinicians.⁸ Recent technological improvements have allowed for inexpensive and efficient dissemination of educational materials, including video lectures, podcasts, online modules, assessment materials, and even entire curricula.⁹

There has been an increase in the awareness of the parallel curriculum involving self-directed and asynchronous learning opportunities. ¹⁰ Several studies report knowledge gained via tele-education is comparable to conventional classroom learning.^11-13 A systematic review of e-learning perceptions among health care students suggested benefits (eg, learning flexibility, pedagogical design, online interactions, basic computer skills, and access to technology) and drawbacks (eg, limited acquisition of clinical skills, internet connection problems, and issues with using educational platforms).¹

The COVID-19 pandemic forced an abrupt cessation of traditional in-person education, forcing educational institutions and medical organizations to transition to telelearning. Solutions in the education field appeared during the pandemic, such as videoconferencing, social media, and telemedicine, that effectively addressed the sudden cessation of in-person medical education.¹⁵

Graduate medical education in neurology residency programs served as an experimental set up for tele-education during the pandemic. Residents from neurology training programs outlined the benefits of a volunteer lecturer-based online didactic program that was established to meet this need, which included exposure to subspeciality topics, access to subspecialist experts not available within the department, exposure to different pedagogic methods, interaction with members of other educational institutions and training programs, career development opportunities, and the potential for forming a community of learning.¹⁶

Not all recent educational developments are technology-based. For example, instruction focused on specific patient experiences, and learning processes that emphasize problem solving and personal responsibility over specific knowledge have been successful in neurology.^17,18 Departments and institutions must be creative in finding ways to fund continuing education, especially when budgets are limited.¹⁹

ANNUAL NEUROLOGY SEMINAR

An annual Veterans Health Administration (VHA) neurology seminar began in 2019 as a 1-day in-person event. Neurologists at the Michael E. DeBakey VA Medical Center in Houston presented in 50-minute sessions. Nonspecialist clinical personnel and neurology clinicians attended the event. Attendees requested making the presentations widely available and regularly repeating the seminar.

The second neurology seminar took place during the COVID-19 pandemic. It was conducted online and advertised across the Veterans Integrated Services Network (VISN) 16. The 1-day program had 204 participants who were primarily nurses (59%) and physicians (21%); 94% agreed with the program objectives (Table 1). Participants could earn CME credits for the 7 presentations primarily by VHA experts.

Based on feedback and a needs assessment, the program expanded in 2021 and 2022. With support from the national VHA neurology office and VHA Employee Education System (EES), the Institute for Learning, Education, and Development (ILEAD), the feedback identified topics that resonate with VHA clinicians. Neurological disorders in the fields of stroke, dementia, and headache were included since veterans with these disorders regularly visit primary care, geriatrics, mental health, and other clinical offices. Updates provided in the diagnosis and treatment of common neurological disorders were well received. Almost all speakers were VHA clinicians, which allowed them to focus on topics relevant to clinical practice at the VHA.

Attendance has increased annually. In 2021, 550 clinicians registered (52% nurses) and 433 completed the postseminar survey (Table 2). In 2022, 635 participants registered and 342 completed evaluations, including attendees from other federal agencies who were invited to participate via EES TRAIN (Training Finder Real-time Affiliate Integrated Network). Forty-seven participants from other federal agencies, including the US Department of Defense, National Institute of Health, and Centers for Disease Control and Prevention, completed the feedback evaluation via TRAIN (Table 3). Participants report high levels of satisfaction each year (mean of 4.5 on a 5-point scale). Respondents preferred conventional lecture presentation and case-based discussions for the teaching format and dementia was the most requested topic for future seminars (Table 4).

The content of each seminar was designed to include . 1 topic relevant to current clinical practice. The 2020 seminar covered topics of cerebrovascular complications of COVID- 19 and living well with neurodegenerative disease in the COVID-19 era. In 2021, the seminar included COVID-19 and neurologic manifestations. In 2022, topics included trends in stroke rehabilitation. In addition, ≥ 1 session addressed neurologic issues within the VHA. In 2020, the VA Deputy National Director of Neurology presented on the VHA stroke systems of care. In 2021, there was a presentation on traumatic brain injury (TBI) in the military. In 2022, sessions covered long term neurologic consequences of TBI and use of telemedicine for neurologic disorders. Feedback on the sessions were positive (eAppendix, available at doi:10.12788/fp.0545).

At the request of the participants, individual presentations were shared via email by the course director and speakers. In collaboration with the EES, each session was recorded and the 2022 seminar was made available to registrants in TMS and EES TRAIN and via the VHA Neurology SharePoint.

DISCUSSION

The annual VHA neurology seminar is a 1-day neurology conference that provides education to general neurologists and other clinicians caring for patients with neurologic disorders. It is the first of its kind neurology education program in the VHA covering most subspecialties in neurology and aims at improving neurologic patient care and access through education. Sessions have covered stroke, epilepsy, sleep, amyotrophic lateral sclerosis, neuropathy, dementia, movement disorders and Parkinson disease, headaches, multiple sclerosis, neurorehabilitation, and telehealth.

The seminar has transitioned from an inperson meeting to a virtual format, making neurology education more convenient and accessible. The virtual format provides the means to increase educational collaborations and share lecture platforms with other federal agencies. The program offers CME credits at no cost to government employees. Recorded lectures can also be asynchronously viewed from the Neurology SharePoint without the ability to earn CME credits. These recordings may be used to educate trainees as well.

The seminar aims to educate all health care professionals caring for patients with neurologic disorders. It aims to eliminate neurophobia, the fear of neural sciences and clinical neurology, and help general practitioners, especially in rural areas, take care of patients with neurologic disorders. The seminars introduce general practitioners to VHA neurology experts; the epilepsy, headache multiple sclerosis, and Parkinson disease centers of excellence; and the national programs for telestroke and teleneurology.

Education Support in the VHA

The EES/ILEAD provides a wide variety of learning opportunities to VHA employees on a broad range of topics, making it one of the largest medical education programs in the country. Pharmacists, social workers, psychologists, therapists, nurses, physician assistants, and physicians have access to certified training opportunities to gain knowledge and skills needed to provide high-quality, veteran-centered care.

A review of geriatrics learning activities through the EES found > 15,000 lectures from 1999 to 2009 for > 300,000 attendees.²⁰ To our knowledge, a review of neurology-related learning activities offered by the EES/ILEAD has not been completed, but the study on geriatrics shows that a similar review would be feasible, given the integrated education system, and helpful in identifying what topics are covered, formats are used, and participants are engaged in neurology education at the VHA. This is a future project planned by the neurology education workgroup.

The EES/ILEAD arranged CME credit for the VHA Neurology Seminar and assisted in organizing an online event with > 500 attendees. Technology support and tools provided by EES during the virtual seminar, such as polling and chat features, kept the audience engaged. Other specialties may similarly value a virtual, all-day seminar format that is efficient and can encourage increased participation from practitioners, nurses, and clinicians.

Future Growth

We plan to increase future participation in the annual neurology seminar with primary care, geriatrics, neurology, and other specialties by instituting an improved and earlier marketing strategy. This includes working with the VHA neurology office to inform neurology practitioners as well as other program offices in the VHA. We intend to host the seminar the same day every year to make it easy for attendees to plan accordingly. In the future we may consider hybrid in-person and virtual modalities if feasible. We plan to focus on reaching out to other government agencies through platforms like TRAIN and the American Academy of Neurology government sections. Securing funding, administrative staff, and protected time in the future may help expand the program further.

Limitations

While a virtual format offers several advantages, using it removes the feel of an in-person meeting, which could be viewed by some attendees as a limitation. The other challenges and drawbacks of transitioning to the virtual platform for a national meeting are similar to those reported in the literature: time zone differences, internet issues, and participants having difficulty using certain online platforms. Attendance could also be limited by scheduling conflicts.¹⁶ Despite a large audience attending the seminar, many clinicians do not get protected time from their institutions. Institutional and leadership support at national and local levels will likely improve participation and help participants earn CME credits. While we are still doing a preliminary needs assessment, a formal needs assessment across federal governmental organizations will be helpful.

CONCLUSIONS

The annual VHA neurology seminar promotes interprofessional education, introduces neurology subspecialty centers of excellence, improves access to renowned neurology experts, and provides neurology-related updates through a VHA lens. The program not only provides educational updates to neurology clinicians, but also increases the confidence of non-neurology clinicians called to care for veterans with neurological disorders in their respective clinics.

Neurologic disorders are major causes of death and disability. Globally, the burden of neurologic disorders continues to increase. The prevalence of disabling neurologic disorders significantly increases with age. As people live longer, health care systems will face increasing demands for treatment, rehabilitation, and support services for neurologic disorders. The scarcity of established modifiable risks for most of the neurologic burden demonstrates how new knowledge is required to develop effective prevention and treatment strategies.¹

A single-center study for chronic headache at a rural institution found that, when combined with public education, clinician education not only can increase access to care but also reduce specialist overuse, hospitalizations, polypharmacy, and emergency department visits.² A predicted shortage of neurologists has sparked increased interest in the field and individual neurology educators are helping fuel its popularity.^3-5

TELE-EDUCATION

Educating the next generation of health professionals is 1 of 4 statutory missions of the US Department of Veterans Affairs (VA).⁶ Tele-education (also known as telelearning and distance learning) deviates from traditional in-person classroom settings, in which the lecture has been a core pedagogic method.⁷ Audio, video, and online technologies provide health education and can overcome geographic barriers for rural and remote clinicians.⁸ Recent technological improvements have allowed for inexpensive and efficient dissemination of educational materials, including video lectures, podcasts, online modules, assessment materials, and even entire curricula.⁹

There has been an increase in the awareness of the parallel curriculum involving self-directed and asynchronous learning opportunities. ¹⁰ Several studies report knowledge gained via tele-education is comparable to conventional classroom learning.^11-13 A systematic review of e-learning perceptions among health care students suggested benefits (eg, learning flexibility, pedagogical design, online interactions, basic computer skills, and access to technology) and drawbacks (eg, limited acquisition of clinical skills, internet connection problems, and issues with using educational platforms).¹

The COVID-19 pandemic forced an abrupt cessation of traditional in-person education, forcing educational institutions and medical organizations to transition to telelearning. Solutions in the education field appeared during the pandemic, such as videoconferencing, social media, and telemedicine, that effectively addressed the sudden cessation of in-person medical education.¹⁵

Graduate medical education in neurology residency programs served as an experimental set up for tele-education during the pandemic. Residents from neurology training programs outlined the benefits of a volunteer lecturer-based online didactic program that was established to meet this need, which included exposure to subspeciality topics, access to subspecialist experts not available within the department, exposure to different pedagogic methods, interaction with members of other educational institutions and training programs, career development opportunities, and the potential for forming a community of learning.¹⁶

Not all recent educational developments are technology-based. For example, instruction focused on specific patient experiences, and learning processes that emphasize problem solving and personal responsibility over specific knowledge have been successful in neurology.^17,18 Departments and institutions must be creative in finding ways to fund continuing education, especially when budgets are limited.¹⁹

ANNUAL NEUROLOGY SEMINAR

An annual Veterans Health Administration (VHA) neurology seminar began in 2019 as a 1-day in-person event. Neurologists at the Michael E. DeBakey VA Medical Center in Houston presented in 50-minute sessions. Nonspecialist clinical personnel and neurology clinicians attended the event. Attendees requested making the presentations widely available and regularly repeating the seminar.

The second neurology seminar took place during the COVID-19 pandemic. It was conducted online and advertised across the Veterans Integrated Services Network (VISN) 16. The 1-day program had 204 participants who were primarily nurses (59%) and physicians (21%); 94% agreed with the program objectives (Table 1). Participants could earn CME credits for the 7 presentations primarily by VHA experts.

Based on feedback and a needs assessment, the program expanded in 2021 and 2022. With support from the national VHA neurology office and VHA Employee Education System (EES), the Institute for Learning, Education, and Development (ILEAD), the feedback identified topics that resonate with VHA clinicians. Neurological disorders in the fields of stroke, dementia, and headache were included since veterans with these disorders regularly visit primary care, geriatrics, mental health, and other clinical offices. Updates provided in the diagnosis and treatment of common neurological disorders were well received. Almost all speakers were VHA clinicians, which allowed them to focus on topics relevant to clinical practice at the VHA.

Attendance has increased annually. In 2021, 550 clinicians registered (52% nurses) and 433 completed the postseminar survey (Table 2). In 2022, 635 participants registered and 342 completed evaluations, including attendees from other federal agencies who were invited to participate via EES TRAIN (Training Finder Real-time Affiliate Integrated Network). Forty-seven participants from other federal agencies, including the US Department of Defense, National Institute of Health, and Centers for Disease Control and Prevention, completed the feedback evaluation via TRAIN (Table 3). Participants report high levels of satisfaction each year (mean of 4.5 on a 5-point scale). Respondents preferred conventional lecture presentation and case-based discussions for the teaching format and dementia was the most requested topic for future seminars (Table 4).

The content of each seminar was designed to include . 1 topic relevant to current clinical practice. The 2020 seminar covered topics of cerebrovascular complications of COVID- 19 and living well with neurodegenerative disease in the COVID-19 era. In 2021, the seminar included COVID-19 and neurologic manifestations. In 2022, topics included trends in stroke rehabilitation. In addition, ≥ 1 session addressed neurologic issues within the VHA. In 2020, the VA Deputy National Director of Neurology presented on the VHA stroke systems of care. In 2021, there was a presentation on traumatic brain injury (TBI) in the military. In 2022, sessions covered long term neurologic consequences of TBI and use of telemedicine for neurologic disorders. Feedback on the sessions were positive (eAppendix, available at doi:10.12788/fp.0545).

At the request of the participants, individual presentations were shared via email by the course director and speakers. In collaboration with the EES, each session was recorded and the 2022 seminar was made available to registrants in TMS and EES TRAIN and via the VHA Neurology SharePoint.

DISCUSSION

The annual VHA neurology seminar is a 1-day neurology conference that provides education to general neurologists and other clinicians caring for patients with neurologic disorders. It is the first of its kind neurology education program in the VHA covering most subspecialties in neurology and aims at improving neurologic patient care and access through education. Sessions have covered stroke, epilepsy, sleep, amyotrophic lateral sclerosis, neuropathy, dementia, movement disorders and Parkinson disease, headaches, multiple sclerosis, neurorehabilitation, and telehealth.

The seminar has transitioned from an inperson meeting to a virtual format, making neurology education more convenient and accessible. The virtual format provides the means to increase educational collaborations and share lecture platforms with other federal agencies. The program offers CME credits at no cost to government employees. Recorded lectures can also be asynchronously viewed from the Neurology SharePoint without the ability to earn CME credits. These recordings may be used to educate trainees as well.

The seminar aims to educate all health care professionals caring for patients with neurologic disorders. It aims to eliminate neurophobia, the fear of neural sciences and clinical neurology, and help general practitioners, especially in rural areas, take care of patients with neurologic disorders. The seminars introduce general practitioners to VHA neurology experts; the epilepsy, headache multiple sclerosis, and Parkinson disease centers of excellence; and the national programs for telestroke and teleneurology.

Education Support in the VHA

The EES/ILEAD provides a wide variety of learning opportunities to VHA employees on a broad range of topics, making it one of the largest medical education programs in the country. Pharmacists, social workers, psychologists, therapists, nurses, physician assistants, and physicians have access to certified training opportunities to gain knowledge and skills needed to provide high-quality, veteran-centered care.

A review of geriatrics learning activities through the EES found > 15,000 lectures from 1999 to 2009 for > 300,000 attendees.²⁰ To our knowledge, a review of neurology-related learning activities offered by the EES/ILEAD has not been completed, but the study on geriatrics shows that a similar review would be feasible, given the integrated education system, and helpful in identifying what topics are covered, formats are used, and participants are engaged in neurology education at the VHA. This is a future project planned by the neurology education workgroup.

The EES/ILEAD arranged CME credit for the VHA Neurology Seminar and assisted in organizing an online event with > 500 attendees. Technology support and tools provided by EES during the virtual seminar, such as polling and chat features, kept the audience engaged. Other specialties may similarly value a virtual, all-day seminar format that is efficient and can encourage increased participation from practitioners, nurses, and clinicians.

Future Growth

We plan to increase future participation in the annual neurology seminar with primary care, geriatrics, neurology, and other specialties by instituting an improved and earlier marketing strategy. This includes working with the VHA neurology office to inform neurology practitioners as well as other program offices in the VHA. We intend to host the seminar the same day every year to make it easy for attendees to plan accordingly. In the future we may consider hybrid in-person and virtual modalities if feasible. We plan to focus on reaching out to other government agencies through platforms like TRAIN and the American Academy of Neurology government sections. Securing funding, administrative staff, and protected time in the future may help expand the program further.

Limitations

While a virtual format offers several advantages, using it removes the feel of an in-person meeting, which could be viewed by some attendees as a limitation. The other challenges and drawbacks of transitioning to the virtual platform for a national meeting are similar to those reported in the literature: time zone differences, internet issues, and participants having difficulty using certain online platforms. Attendance could also be limited by scheduling conflicts.¹⁶ Despite a large audience attending the seminar, many clinicians do not get protected time from their institutions. Institutional and leadership support at national and local levels will likely improve participation and help participants earn CME credits. While we are still doing a preliminary needs assessment, a formal needs assessment across federal governmental organizations will be helpful.

CONCLUSIONS

The annual VHA neurology seminar promotes interprofessional education, introduces neurology subspecialty centers of excellence, improves access to renowned neurology experts, and provides neurology-related updates through a VHA lens. The program not only provides educational updates to neurology clinicians, but also increases the confidence of non-neurology clinicians called to care for veterans with neurological disorders in their respective clinics.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Donepezil was associated with improved verbal memory and enhanced recall and processing speed, compared with placebo, in patients with severe traumatic brain injury (TBI), with a favorable safety profile despite mild to moderate gastrointestinal side effects.

METHODOLOGY:

• A four-site, randomized, parallel-group, double-blind, placebo-controlled, 10-week clinical trial (MEMRI-TBI-D) was conducted between 2013 and 2019 to evaluate the efficacy of donepezil for verbal memory impairments following severe TBI.
• 75 adults (75% men; mean age, 37 years) with complicated mild, moderate, or severe nonpenetrating TBI at least 6 months prior to study participation were included and randomly assigned to receive donepezil (n = 37) or placebo (n = 38).
• Participants received 5 mg donepezil daily or matching placebo for 2 weeks, then donepezil at 10 mg daily or matching placebo for 8 weeks; treatment was discontinued at 10 weeks, with an additional 4-week observation period.
• Verbal memory was assessed using the Hopkins Verbal Learning Test–Revised (HVLT-R). The primary outcome measure was verbal learning, evaluated through the HVLT-R total recall (ie, Total Trials 1-3) score.

TAKEAWAY:

• Compared with placebo, donepezil was associated with significantly greater improvements in verbal learning in both modified intent-to-treat and per-protocol analyses (P = .034 and .036, respectively).
• Treatment-responder rates were significantly higher in the donepezil group than in the placebo group (42 vs 18%; P = .03), with donepezil responders showing significant improvements in delayed recall and processing speed.
• Although there were no serious adverse events in either group, treatment-emergent adverse events were significantly more common in the donepezil group vs placebo (46% vs 8%; P < .001). No serious adverse events occurred in either group.
• Diarrhea and nausea were significantly more common in the donepezil group than in the placebo group (Fisher’s exact test: diarrhea, P = .03; nausea, P = .01).

IN PRACTICE:

“This study demonstrates the efficacy of donepezil on severe, persistent verbal memory impairments after predominantly severe TBI, with significant benefit for a subset of persons with such injuries, as well as a relatively favorable safety and tolerability profile,” the investigators wrote.

SOURCE:

The study was led by David B. Arciniegas, MD, University of Colorado School of Medicine, Aurora. It was published online in The Journal of Neuropsychiatry and Clinical Neurosciences.

LIMITATIONS:

The study included a relatively small sample with predominantly severe TBI requiring hospitalization and inpatient rehabilitation. The sample characteristics limit the generalizability of the findings to persons with other severities of TBI, other types of memory impairments, or more complex neuropsychiatric presentations. The study population had an average of 14 years of education, making generalizability to individuals with lower education levels uncertain. Additionally, while measures of information processing speed and immediate auditory attention were included, specific measures of sustained or selective attention were not, making it difficult to rule out improvements in higher-level attention as potential contributors to the observed verbal memory performance improvements.

DISCLOSURES:

The study was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research, with in-kind support from TIRR Memorial Hermann. Four authors disclosed various financial and professional affiliations, including advisory roles with pharmaceutical and diagnostic companies, support from institutional awards, and involvement in programs funded by external organizations. One author served as the editor of The Journal of Neuropsychiatry and Clinical Neurosciences, with an independent editor overseeing the review and publication process for this article.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Donepezil was associated with improved verbal memory and enhanced recall and processing speed, compared with placebo, in patients with severe traumatic brain injury (TBI), with a favorable safety profile despite mild to moderate gastrointestinal side effects.

METHODOLOGY:

• A four-site, randomized, parallel-group, double-blind, placebo-controlled, 10-week clinical trial (MEMRI-TBI-D) was conducted between 2013 and 2019 to evaluate the efficacy of donepezil for verbal memory impairments following severe TBI.
• 75 adults (75% men; mean age, 37 years) with complicated mild, moderate, or severe nonpenetrating TBI at least 6 months prior to study participation were included and randomly assigned to receive donepezil (n = 37) or placebo (n = 38).
• Participants received 5 mg donepezil daily or matching placebo for 2 weeks, then donepezil at 10 mg daily or matching placebo for 8 weeks; treatment was discontinued at 10 weeks, with an additional 4-week observation period.
• Verbal memory was assessed using the Hopkins Verbal Learning Test–Revised (HVLT-R). The primary outcome measure was verbal learning, evaluated through the HVLT-R total recall (ie, Total Trials 1-3) score.

TAKEAWAY:

• Compared with placebo, donepezil was associated with significantly greater improvements in verbal learning in both modified intent-to-treat and per-protocol analyses (P = .034 and .036, respectively).
• Treatment-responder rates were significantly higher in the donepezil group than in the placebo group (42 vs 18%; P = .03), with donepezil responders showing significant improvements in delayed recall and processing speed.
• Although there were no serious adverse events in either group, treatment-emergent adverse events were significantly more common in the donepezil group vs placebo (46% vs 8%; P < .001). No serious adverse events occurred in either group.
• Diarrhea and nausea were significantly more common in the donepezil group than in the placebo group (Fisher’s exact test: diarrhea, P = .03; nausea, P = .01).

IN PRACTICE:

“This study demonstrates the efficacy of donepezil on severe, persistent verbal memory impairments after predominantly severe TBI, with significant benefit for a subset of persons with such injuries, as well as a relatively favorable safety and tolerability profile,” the investigators wrote.

SOURCE:

The study was led by David B. Arciniegas, MD, University of Colorado School of Medicine, Aurora. It was published online in The Journal of Neuropsychiatry and Clinical Neurosciences.

LIMITATIONS:

The study included a relatively small sample with predominantly severe TBI requiring hospitalization and inpatient rehabilitation. The sample characteristics limit the generalizability of the findings to persons with other severities of TBI, other types of memory impairments, or more complex neuropsychiatric presentations. The study population had an average of 14 years of education, making generalizability to individuals with lower education levels uncertain. Additionally, while measures of information processing speed and immediate auditory attention were included, specific measures of sustained or selective attention were not, making it difficult to rule out improvements in higher-level attention as potential contributors to the observed verbal memory performance improvements.

DISCLOSURES:

The study was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research, with in-kind support from TIRR Memorial Hermann. Four authors disclosed various financial and professional affiliations, including advisory roles with pharmaceutical and diagnostic companies, support from institutional awards, and involvement in programs funded by external organizations. One author served as the editor of The Journal of Neuropsychiatry and Clinical Neurosciences, with an independent editor overseeing the review and publication process for this article.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Donepezil was associated with improved verbal memory and enhanced recall and processing speed, compared with placebo, in patients with severe traumatic brain injury (TBI), with a favorable safety profile despite mild to moderate gastrointestinal side effects.

METHODOLOGY:

• A four-site, randomized, parallel-group, double-blind, placebo-controlled, 10-week clinical trial (MEMRI-TBI-D) was conducted between 2013 and 2019 to evaluate the efficacy of donepezil for verbal memory impairments following severe TBI.
• 75 adults (75% men; mean age, 37 years) with complicated mild, moderate, or severe nonpenetrating TBI at least 6 months prior to study participation were included and randomly assigned to receive donepezil (n = 37) or placebo (n = 38).
• Participants received 5 mg donepezil daily or matching placebo for 2 weeks, then donepezil at 10 mg daily or matching placebo for 8 weeks; treatment was discontinued at 10 weeks, with an additional 4-week observation period.
• Verbal memory was assessed using the Hopkins Verbal Learning Test–Revised (HVLT-R). The primary outcome measure was verbal learning, evaluated through the HVLT-R total recall (ie, Total Trials 1-3) score.

TAKEAWAY:

• Compared with placebo, donepezil was associated with significantly greater improvements in verbal learning in both modified intent-to-treat and per-protocol analyses (P = .034 and .036, respectively).
• Treatment-responder rates were significantly higher in the donepezil group than in the placebo group (42 vs 18%; P = .03), with donepezil responders showing significant improvements in delayed recall and processing speed.
• Although there were no serious adverse events in either group, treatment-emergent adverse events were significantly more common in the donepezil group vs placebo (46% vs 8%; P < .001). No serious adverse events occurred in either group.
• Diarrhea and nausea were significantly more common in the donepezil group than in the placebo group (Fisher’s exact test: diarrhea, P = .03; nausea, P = .01).

IN PRACTICE:

“This study demonstrates the efficacy of donepezil on severe, persistent verbal memory impairments after predominantly severe TBI, with significant benefit for a subset of persons with such injuries, as well as a relatively favorable safety and tolerability profile,” the investigators wrote.

SOURCE:

The study was led by David B. Arciniegas, MD, University of Colorado School of Medicine, Aurora. It was published online in The Journal of Neuropsychiatry and Clinical Neurosciences.

LIMITATIONS:

The study included a relatively small sample with predominantly severe TBI requiring hospitalization and inpatient rehabilitation. The sample characteristics limit the generalizability of the findings to persons with other severities of TBI, other types of memory impairments, or more complex neuropsychiatric presentations. The study population had an average of 14 years of education, making generalizability to individuals with lower education levels uncertain. Additionally, while measures of information processing speed and immediate auditory attention were included, specific measures of sustained or selective attention were not, making it difficult to rule out improvements in higher-level attention as potential contributors to the observed verbal memory performance improvements.

DISCLOSURES:

The study was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research, with in-kind support from TIRR Memorial Hermann. Four authors disclosed various financial and professional affiliations, including advisory roles with pharmaceutical and diagnostic companies, support from institutional awards, and involvement in programs funded by external organizations. One author served as the editor of The Journal of Neuropsychiatry and Clinical Neurosciences, with an independent editor overseeing the review and publication process for this article.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Researchers are gaining new insight into the relationship between the human cytomegalovirus (HCMV), a common herpes virus found in the gut, and the immune response associated with CD83 antibody in some individuals with Alzheimer’s disease (AD).

Using tissue samples from deceased donors with AD, the study showed CD83-positive (CD83+) microglia in the superior frontal gyrus (SFG) are significantly associated with elevated immunoglobulin gamma 4 (IgG4) and HCMV in the transverse colon (TC), increased anti-HCMV IgG4 in the cerebrospinal fluid (CSF), and both HCMV and IgG4 in the SFG and vagus nerve.

“Our results indicate a complex, cross-tissue interaction between HCMV and the host adaptive immune response associated with CD83+ microglia in persons with AD,” noted the investigators, including Benjamin P. Readhead, MBBS, research associate professor, ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe.

The results suggest antiviral therapy in patients with biomarker evidence of HCMV, IgG4, or CD83+ microglia might ward off dementia.

“We’re preparing to conduct a clinical trial to evaluate whether careful use of existing antivirals might be clinically helpful in preventing or slowing progression of CD83+ associated Alzheimer’s disease,” Readhead said in an interview.

The study was published on December 19, 2024, in Alzheimer’s & Dementia.

 

Vagus Nerve a Potential Pathway?

CMV is a common virus. In the United States, nearly one in three children are already infected with CMV by age 5 years. Over half the adults have been infected with CMV by age 40 years, the Centers for Disease Control and Prevention reported.

It is typically passed through bodily fluids and spread only when the virus is active. It’s not considered a sexually transmitted disease.

Compared with other IgG subclasses, IgG4 is believed to be a less inflammatory, and therefore less damaging, immune response. But this response may be less effective at clearing infections and allow invasion of HCMV into the brain.

Experts speculate HCMV may travel via the vagus nerve from the colon to the brain where it triggers the onset of AD. 

The researchers previously found a CD83+ microglial subtype in the SFG of 47% of brain donors with AD vs 25% of unaffected control individuals. They reported this subtype is associated with increased IgG4 in the TC.

The current analysis extends investigations of the potential etiology and clinicopathologic relevance of CD83+ microglia in the context of AD.

Researchers conducted experiments using donated tissue samples from deceased patients with AD and control individuals. Sources for these samples included the Banner cohort, for whom classifications for the presence of CD83+ microglia were available, as were tissue samples from the SFG, TC, and vagus nerve, and the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), in which participants without known dementia are evaluated annually.

From the Banner cohort, researchers completed immunohistochemistry (IHC) studies on 34 SFG samples (21 AD and 13 control individuals) and included 25 TC samples (13 AD and 12 control individuals) and 8 vagal nerve samples (6 AD and 2 control individuals) in the study. From the ROSMAP cohort, they completed IHC studies on 27 prefrontal cortex samples from individuals with AD.

They carefully selected these samples to ensure matching for critical factors such as postmortem interval, age, and sex, as well as other relevant covariates, said the authors.

The study verified that CD83+ microglia are associated with IgG4 and HCMV in the TC and showed a significant association between CD83+ microglia and IgG4 immunoreactivity in the TC.

Investigators confirmed HCMV positivity in all nine CD83+ TC samples evaluated and in one CD83– TC sample, indicating a strong positive association between HCMV within the TC and CD83+ microglia within the SFG.

HCMV IgG seroprevalence is common, varies by age and comorbidity, and is present in 79% of 85-year-olds, the investigators noted. “Despite this, we note that HCMV presence in the TC was not ubiquitous and was significantly associated with CD83+ microglia and HCMV in the SFG,” they wrote.

This observation, they added, “may help reconcile how a common pathogen might contribute to a disease that most individuals do not develop.”

The experiments also uncovered increased anti-HCMV IgG4 in the CSF and evidence of HCMV and IgG4 in the vagus nerve.

“Overall, the histochemical staining patterns observed in TC, SFG, and vagus nerve of CD83+ subjects are consistent with active HCMV infection,” the investigators wrote. “Taken together, these results indicate a multiorgan presence of IgG4 and HCMV in subjects with CD83+ microglia within the SFG,” they added.

 

Accelerated AD Pathology

The team showed HCMV infection accelerates production of two pathologic features of AD — amyloid beta (Abeta) and tau — and causes neuronal death. “We observed high, positive correlations between the abundance of HCMV, and both Abeta42 and pTau-212,” they wrote.

As HCMV histochemistry is consistent with an active HCMV infection, the findings “may indicate an opportunity for the administration of antiviral therapy in subjects with AD and biomarker evidence of HCMV, IgG4, or CD83+ microglia,” they added.

In addition to planning a clinical trial of existing antivirals, the research team is developing a blood test that can help identify patients with an active HCMV infection who might benefit from such an intervention, said Readhead.

But he emphasized that the research is still in its infancy. “Our study is best understood as a series of interesting scientific findings that warrant further exploration, replication, and validation in additional study populations.”

Although it’s too early for the study to impact practice, “we’re motivated to understand whether these findings have implications for clinical care,” he added.

 

Tipping the Balance

A number of experts have weighed in on the research via the Science Media Center, an independent forum featuring the voices and views on science news from experts in the field.

Andrew Doig, PhD, professor, Division of Neuroscience, University of Manchester in England, said the new work supports the hypothesis that HCMV might be a trigger that tips the balance from a healthy brain to one with dementia. “If so, antiviral drugs against HCMV might be beneficial in reducing the risk of AD.”

Doig noted newly approved drugs for AD are expensive, provide only a small benefit, and have significant risks, such as causing brain hemorrhages. “Antiviral drugs are an attractive alternative that are well worth exploring.”

Richard Oakley, PhD, associate director of research and innovation, Alzheimer’s Society, cautioned the study only established a connection and didn’t directly show the virus leads to AD. “Also, the virus is not found in the brain of everyone with Alzheimer’s disease, the most common form of dementia.”

The significance of the new findings is “far from clear,” commented William McEwan, PhD, group leader at the UK Dementia Research Institute at Cambridge, England. “The study does not address how common this infection is in people without Alzheimer’s and therefore cannot by itself suggest that HCMV infection, or the associated immune response, is a driver of disease.”

The experts agreed follow-up research is needed to confirm these new findings and understand what they mean.

The study received support from the National Institute on Aging, National Institutes of Health, Global Lyme Alliance, National Institute of Neurological Disorders and Stroke, Arizona Alzheimer’s Consortium, The Benter Foundation, and NOMIS Stiftung. Readhead is a coinventor on a patent application for an IgG4-based peripheral biomarker for the detection of CD83+ microglia. Doig is a founder, director, and consultant for PharmaKure, which works on AD drugs and diagnostics, although not on viruses. He has cowritten a review on Viral Involvement in Alzheimer’s Disease. McEwan reported receiving research funding from Takeda Pharmaceuticals and is a founder and consultant to Trimtech Therapeutics.

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

Researchers are gaining new insight into the relationship between the human cytomegalovirus (HCMV), a common herpes virus found in the gut, and the immune response associated with CD83 antibody in some individuals with Alzheimer’s disease (AD).

Using tissue samples from deceased donors with AD, the study showed CD83-positive (CD83+) microglia in the superior frontal gyrus (SFG) are significantly associated with elevated immunoglobulin gamma 4 (IgG4) and HCMV in the transverse colon (TC), increased anti-HCMV IgG4 in the cerebrospinal fluid (CSF), and both HCMV and IgG4 in the SFG and vagus nerve.

“Our results indicate a complex, cross-tissue interaction between HCMV and the host adaptive immune response associated with CD83+ microglia in persons with AD,” noted the investigators, including Benjamin P. Readhead, MBBS, research associate professor, ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe.

The results suggest antiviral therapy in patients with biomarker evidence of HCMV, IgG4, or CD83+ microglia might ward off dementia.

“We’re preparing to conduct a clinical trial to evaluate whether careful use of existing antivirals might be clinically helpful in preventing or slowing progression of CD83+ associated Alzheimer’s disease,” Readhead said in an interview.

The study was published on December 19, 2024, in Alzheimer’s & Dementia.

 

Vagus Nerve a Potential Pathway?

CMV is a common virus. In the United States, nearly one in three children are already infected with CMV by age 5 years. Over half the adults have been infected with CMV by age 40 years, the Centers for Disease Control and Prevention reported.

It is typically passed through bodily fluids and spread only when the virus is active. It’s not considered a sexually transmitted disease.

Compared with other IgG subclasses, IgG4 is believed to be a less inflammatory, and therefore less damaging, immune response. But this response may be less effective at clearing infections and allow invasion of HCMV into the brain.

Experts speculate HCMV may travel via the vagus nerve from the colon to the brain where it triggers the onset of AD. 

The researchers previously found a CD83+ microglial subtype in the SFG of 47% of brain donors with AD vs 25% of unaffected control individuals. They reported this subtype is associated with increased IgG4 in the TC.

The current analysis extends investigations of the potential etiology and clinicopathologic relevance of CD83+ microglia in the context of AD.

Researchers conducted experiments using donated tissue samples from deceased patients with AD and control individuals. Sources for these samples included the Banner cohort, for whom classifications for the presence of CD83+ microglia were available, as were tissue samples from the SFG, TC, and vagus nerve, and the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), in which participants without known dementia are evaluated annually.

From the Banner cohort, researchers completed immunohistochemistry (IHC) studies on 34 SFG samples (21 AD and 13 control individuals) and included 25 TC samples (13 AD and 12 control individuals) and 8 vagal nerve samples (6 AD and 2 control individuals) in the study. From the ROSMAP cohort, they completed IHC studies on 27 prefrontal cortex samples from individuals with AD.

They carefully selected these samples to ensure matching for critical factors such as postmortem interval, age, and sex, as well as other relevant covariates, said the authors.

The study verified that CD83+ microglia are associated with IgG4 and HCMV in the TC and showed a significant association between CD83+ microglia and IgG4 immunoreactivity in the TC.

Investigators confirmed HCMV positivity in all nine CD83+ TC samples evaluated and in one CD83– TC sample, indicating a strong positive association between HCMV within the TC and CD83+ microglia within the SFG.

HCMV IgG seroprevalence is common, varies by age and comorbidity, and is present in 79% of 85-year-olds, the investigators noted. “Despite this, we note that HCMV presence in the TC was not ubiquitous and was significantly associated with CD83+ microglia and HCMV in the SFG,” they wrote.

This observation, they added, “may help reconcile how a common pathogen might contribute to a disease that most individuals do not develop.”

The experiments also uncovered increased anti-HCMV IgG4 in the CSF and evidence of HCMV and IgG4 in the vagus nerve.

“Overall, the histochemical staining patterns observed in TC, SFG, and vagus nerve of CD83+ subjects are consistent with active HCMV infection,” the investigators wrote. “Taken together, these results indicate a multiorgan presence of IgG4 and HCMV in subjects with CD83+ microglia within the SFG,” they added.

 

Accelerated AD Pathology

The team showed HCMV infection accelerates production of two pathologic features of AD — amyloid beta (Abeta) and tau — and causes neuronal death. “We observed high, positive correlations between the abundance of HCMV, and both Abeta42 and pTau-212,” they wrote.

As HCMV histochemistry is consistent with an active HCMV infection, the findings “may indicate an opportunity for the administration of antiviral therapy in subjects with AD and biomarker evidence of HCMV, IgG4, or CD83+ microglia,” they added.

In addition to planning a clinical trial of existing antivirals, the research team is developing a blood test that can help identify patients with an active HCMV infection who might benefit from such an intervention, said Readhead.

But he emphasized that the research is still in its infancy. “Our study is best understood as a series of interesting scientific findings that warrant further exploration, replication, and validation in additional study populations.”

Although it’s too early for the study to impact practice, “we’re motivated to understand whether these findings have implications for clinical care,” he added.

 

Tipping the Balance

A number of experts have weighed in on the research via the Science Media Center, an independent forum featuring the voices and views on science news from experts in the field.

Andrew Doig, PhD, professor, Division of Neuroscience, University of Manchester in England, said the new work supports the hypothesis that HCMV might be a trigger that tips the balance from a healthy brain to one with dementia. “If so, antiviral drugs against HCMV might be beneficial in reducing the risk of AD.”

Doig noted newly approved drugs for AD are expensive, provide only a small benefit, and have significant risks, such as causing brain hemorrhages. “Antiviral drugs are an attractive alternative that are well worth exploring.”

Richard Oakley, PhD, associate director of research and innovation, Alzheimer’s Society, cautioned the study only established a connection and didn’t directly show the virus leads to AD. “Also, the virus is not found in the brain of everyone with Alzheimer’s disease, the most common form of dementia.”

The significance of the new findings is “far from clear,” commented William McEwan, PhD, group leader at the UK Dementia Research Institute at Cambridge, England. “The study does not address how common this infection is in people without Alzheimer’s and therefore cannot by itself suggest that HCMV infection, or the associated immune response, is a driver of disease.”

The experts agreed follow-up research is needed to confirm these new findings and understand what they mean.

The study received support from the National Institute on Aging, National Institutes of Health, Global Lyme Alliance, National Institute of Neurological Disorders and Stroke, Arizona Alzheimer’s Consortium, The Benter Foundation, and NOMIS Stiftung. Readhead is a coinventor on a patent application for an IgG4-based peripheral biomarker for the detection of CD83+ microglia. Doig is a founder, director, and consultant for PharmaKure, which works on AD drugs and diagnostics, although not on viruses. He has cowritten a review on Viral Involvement in Alzheimer’s Disease. McEwan reported receiving research funding from Takeda Pharmaceuticals and is a founder and consultant to Trimtech Therapeutics.

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

Researchers are gaining new insight into the relationship between the human cytomegalovirus (HCMV), a common herpes virus found in the gut, and the immune response associated with CD83 antibody in some individuals with Alzheimer’s disease (AD).

Using tissue samples from deceased donors with AD, the study showed CD83-positive (CD83+) microglia in the superior frontal gyrus (SFG) are significantly associated with elevated immunoglobulin gamma 4 (IgG4) and HCMV in the transverse colon (TC), increased anti-HCMV IgG4 in the cerebrospinal fluid (CSF), and both HCMV and IgG4 in the SFG and vagus nerve.

“Our results indicate a complex, cross-tissue interaction between HCMV and the host adaptive immune response associated with CD83+ microglia in persons with AD,” noted the investigators, including Benjamin P. Readhead, MBBS, research associate professor, ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe.

The results suggest antiviral therapy in patients with biomarker evidence of HCMV, IgG4, or CD83+ microglia might ward off dementia.

“We’re preparing to conduct a clinical trial to evaluate whether careful use of existing antivirals might be clinically helpful in preventing or slowing progression of CD83+ associated Alzheimer’s disease,” Readhead said in an interview.

The study was published on December 19, 2024, in Alzheimer’s & Dementia.

 

Vagus Nerve a Potential Pathway?

CMV is a common virus. In the United States, nearly one in three children are already infected with CMV by age 5 years. Over half the adults have been infected with CMV by age 40 years, the Centers for Disease Control and Prevention reported.

It is typically passed through bodily fluids and spread only when the virus is active. It’s not considered a sexually transmitted disease.

Compared with other IgG subclasses, IgG4 is believed to be a less inflammatory, and therefore less damaging, immune response. But this response may be less effective at clearing infections and allow invasion of HCMV into the brain.

Experts speculate HCMV may travel via the vagus nerve from the colon to the brain where it triggers the onset of AD. 

The researchers previously found a CD83+ microglial subtype in the SFG of 47% of brain donors with AD vs 25% of unaffected control individuals. They reported this subtype is associated with increased IgG4 in the TC.

The current analysis extends investigations of the potential etiology and clinicopathologic relevance of CD83+ microglia in the context of AD.

Researchers conducted experiments using donated tissue samples from deceased patients with AD and control individuals. Sources for these samples included the Banner cohort, for whom classifications for the presence of CD83+ microglia were available, as were tissue samples from the SFG, TC, and vagus nerve, and the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), in which participants without known dementia are evaluated annually.

From the Banner cohort, researchers completed immunohistochemistry (IHC) studies on 34 SFG samples (21 AD and 13 control individuals) and included 25 TC samples (13 AD and 12 control individuals) and 8 vagal nerve samples (6 AD and 2 control individuals) in the study. From the ROSMAP cohort, they completed IHC studies on 27 prefrontal cortex samples from individuals with AD.

They carefully selected these samples to ensure matching for critical factors such as postmortem interval, age, and sex, as well as other relevant covariates, said the authors.

The study verified that CD83+ microglia are associated with IgG4 and HCMV in the TC and showed a significant association between CD83+ microglia and IgG4 immunoreactivity in the TC.

Investigators confirmed HCMV positivity in all nine CD83+ TC samples evaluated and in one CD83– TC sample, indicating a strong positive association between HCMV within the TC and CD83+ microglia within the SFG.

HCMV IgG seroprevalence is common, varies by age and comorbidity, and is present in 79% of 85-year-olds, the investigators noted. “Despite this, we note that HCMV presence in the TC was not ubiquitous and was significantly associated with CD83+ microglia and HCMV in the SFG,” they wrote.

This observation, they added, “may help reconcile how a common pathogen might contribute to a disease that most individuals do not develop.”

The experiments also uncovered increased anti-HCMV IgG4 in the CSF and evidence of HCMV and IgG4 in the vagus nerve.

“Overall, the histochemical staining patterns observed in TC, SFG, and vagus nerve of CD83+ subjects are consistent with active HCMV infection,” the investigators wrote. “Taken together, these results indicate a multiorgan presence of IgG4 and HCMV in subjects with CD83+ microglia within the SFG,” they added.

 

Accelerated AD Pathology

The team showed HCMV infection accelerates production of two pathologic features of AD — amyloid beta (Abeta) and tau — and causes neuronal death. “We observed high, positive correlations between the abundance of HCMV, and both Abeta42 and pTau-212,” they wrote.

As HCMV histochemistry is consistent with an active HCMV infection, the findings “may indicate an opportunity for the administration of antiviral therapy in subjects with AD and biomarker evidence of HCMV, IgG4, or CD83+ microglia,” they added.

In addition to planning a clinical trial of existing antivirals, the research team is developing a blood test that can help identify patients with an active HCMV infection who might benefit from such an intervention, said Readhead.

But he emphasized that the research is still in its infancy. “Our study is best understood as a series of interesting scientific findings that warrant further exploration, replication, and validation in additional study populations.”

Although it’s too early for the study to impact practice, “we’re motivated to understand whether these findings have implications for clinical care,” he added.

 

Tipping the Balance

A number of experts have weighed in on the research via the Science Media Center, an independent forum featuring the voices and views on science news from experts in the field.

Andrew Doig, PhD, professor, Division of Neuroscience, University of Manchester in England, said the new work supports the hypothesis that HCMV might be a trigger that tips the balance from a healthy brain to one with dementia. “If so, antiviral drugs against HCMV might be beneficial in reducing the risk of AD.”

Doig noted newly approved drugs for AD are expensive, provide only a small benefit, and have significant risks, such as causing brain hemorrhages. “Antiviral drugs are an attractive alternative that are well worth exploring.”

Richard Oakley, PhD, associate director of research and innovation, Alzheimer’s Society, cautioned the study only established a connection and didn’t directly show the virus leads to AD. “Also, the virus is not found in the brain of everyone with Alzheimer’s disease, the most common form of dementia.”

The significance of the new findings is “far from clear,” commented William McEwan, PhD, group leader at the UK Dementia Research Institute at Cambridge, England. “The study does not address how common this infection is in people without Alzheimer’s and therefore cannot by itself suggest that HCMV infection, or the associated immune response, is a driver of disease.”

The experts agreed follow-up research is needed to confirm these new findings and understand what they mean.

The study received support from the National Institute on Aging, National Institutes of Health, Global Lyme Alliance, National Institute of Neurological Disorders and Stroke, Arizona Alzheimer’s Consortium, The Benter Foundation, and NOMIS Stiftung. Readhead is a coinventor on a patent application for an IgG4-based peripheral biomarker for the detection of CD83+ microglia. Doig is a founder, director, and consultant for PharmaKure, which works on AD drugs and diagnostics, although not on viruses. He has cowritten a review on Viral Involvement in Alzheimer’s Disease. McEwan reported receiving research funding from Takeda Pharmaceuticals and is a founder and consultant to Trimtech Therapeutics.

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

Children aged 5-12 years with concussion have similar recovery trajectories, regardless of whether the injury is linked to sports or to other causes, such as falls, new data indicated. 

“With that result, it means we don’t need to change management protocols” depending on the cause of the concussion, study author Andrée-Anne Ledoux, PhD, a scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Ontario, Canada, said in an interview. “That’s kind of good news. We’re applying the right management protocols with them.”

The data were published on December 4 in JAMA Network Open.

 

Secondary Analysis

The results stem from a planned secondary analysis of the prospective Predicting and Preventing Postconcussive Problems in Pediatrics study. Conducted from August 2013 to June 2015 at nine pediatric emergency departments in Canada, it included children of different ages (5 to < 18 years), genders, demographic characteristics, and comorbidities. All participants had a concussion.

The secondary analysis focused on study participants who were aged 5-12 years and had presented within 48 hours of injury. The primary outcome was symptom change, which was defined as current ratings minus preinjury ratings, across time (1, 2, 4, 8, and 12 weeks), measured using the Post-Concussion Symptom Inventory.

No significant differences in postinjury recovery curves were found between participants with sport-related concussions (SRC) and those with non-SRC. The latter injuries resulted from causes such as falls and objects dropped on heads. SRC and non-SRC showed a nonlinear association with time, with symptoms decreasing over time.

Perhaps surprisingly, the researchers also reported a higher rate of persisting symptoms after concussion (PSAC) following limited contact sports than following contact sports such as hockey, soccer, rugby, lacrosse, and football. Limited contact sports include activities such as bicycling, horseback riding, tobogganing, gymnastics, and cheerleading.

This finding suggests that the management of SRC may not require distinct strategies based on sports classification, the researchers wrote. “Instead, it may be more appropriate for clinicians to consider the specific dynamics of the activity, such as velocity and risk of falls from heights. This nuanced perspective can aid in assessing the likelihood of persisting symptoms.” The researchers urged more investigation of this question. “A larger sample with more information on injury height and velocity would be required to confirm whether an association exists.”

In addition, the researchers cited guidelines that include a recommendation for a gradual return to low to moderate physical and cognitive activity starting 24-48 hours after a concussion at a level that does not result in recurrence or exacerbation of symptoms.

“Children do need to return to their lives. They need to return to school,” said Ledoux. “They can have accommodations while they return to school, but just returning to school has huge benefits because you’re reintegrating the child into their typical lifestyle and socialization as well.”

A potential limitation of the study was its reliance on participants who had been seen in emergency departments and thus may have been experiencing more intense symptoms than those seen elsewhere.

The researchers also excluded cases of concussion resulting from assaults and motor vehicle crashes. This decision may explain why they didn’t reproduce the previous observation that patients with SRC tended to recover faster than those with concussions from other causes.

Injuries resulting from assaults and motor vehicle crashes can involve damage beyond concussions, Ledoux said. Including these cases would not allow for an apples-to-apples comparison of SRC and non-SRC.

 

‘Don’t Cocoon Kids’

The authors of an accompanying editorial wrote that the researchers had done “a beautiful job highlighting this important nuance.” Noncontact sports with seemingly little risk “actually carry substantial risks when one imagines the high-impact forces that can occur with a fall from height, albeit rare,” Scott Zuckerman, MD, MPH, assistant professor of neurological surgery at Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues wrote.

The new analysis suggests a need to rethink a “somewhat archaic way of classifying sport risk, which may oversimplify how we categorize risk of brain and spine injuries.”

The commentary also noted how the researchers used the term PSAC to describe lingering symptoms instead of more widely used terms like “persistent postconcussive symptoms” or “postconcussive syndrome.”

“These traditional terms often connote a permanent syndrome or assumption that the concussion itself is solely responsible for 100% of symptoms, which can be harmful to a patient’s recovery,” the editorialists wrote. “Conversely, PSAC offers room for the clinician to discuss how other causes may be maintaining, magnifying, or mimicking concussion symptoms.”

Commenting on the findings, Richard Figler, MD, an orthopedic surgeon at the Cleveland Clinic, Cleveland, praised the researchers for addressing concussion in younger children, a field in which little research has been conducted. The research supports the current approaches to treatment. The approach has shifted toward easing children quickly and safely back into normal routines. “We don’t cocoon kids. We don’t send them to dark rooms,” Figler added.

He also commended the researchers’ decision to examine data about concussions linked to limited contact sports. In contact sports, participants may be more likely to anticipate and prepare for a hit. That’s not the case with injuries sustained in limited contact sports.

“Dodgeball is basically a sucker punch. That’s why these kids have so many concussions,” said Figler. “They typically don’t see the ball coming, or they can’t get out of the way, and they can’t tense themselves to take that blow.”

The Predicting and Preventing Postconcussive Problems in Pediatrics study was funded by the Canadian Institutes of Health Research and the Canadian Institutes of Health Research-Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team. Ledoux reported receiving grants from the Children’s Hospital of Eastern Ontario Foundation, Ontario Brain Institute, and University of Ottawa Brain and Mind Research Institute. She received nonfinancial support from Mobio Interactive outside the submitted work. Zuckerman reported receiving personal fees from the National Football League and Medtronic outside the submitted work. Figler had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Children aged 5-12 years with concussion have similar recovery trajectories, regardless of whether the injury is linked to sports or to other causes, such as falls, new data indicated. 

“With that result, it means we don’t need to change management protocols” depending on the cause of the concussion, study author Andrée-Anne Ledoux, PhD, a scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Ontario, Canada, said in an interview. “That’s kind of good news. We’re applying the right management protocols with them.”

The data were published on December 4 in JAMA Network Open.

 

Secondary Analysis

The results stem from a planned secondary analysis of the prospective Predicting and Preventing Postconcussive Problems in Pediatrics study. Conducted from August 2013 to June 2015 at nine pediatric emergency departments in Canada, it included children of different ages (5 to < 18 years), genders, demographic characteristics, and comorbidities. All participants had a concussion.

The secondary analysis focused on study participants who were aged 5-12 years and had presented within 48 hours of injury. The primary outcome was symptom change, which was defined as current ratings minus preinjury ratings, across time (1, 2, 4, 8, and 12 weeks), measured using the Post-Concussion Symptom Inventory.

No significant differences in postinjury recovery curves were found between participants with sport-related concussions (SRC) and those with non-SRC. The latter injuries resulted from causes such as falls and objects dropped on heads. SRC and non-SRC showed a nonlinear association with time, with symptoms decreasing over time.

Perhaps surprisingly, the researchers also reported a higher rate of persisting symptoms after concussion (PSAC) following limited contact sports than following contact sports such as hockey, soccer, rugby, lacrosse, and football. Limited contact sports include activities such as bicycling, horseback riding, tobogganing, gymnastics, and cheerleading.

This finding suggests that the management of SRC may not require distinct strategies based on sports classification, the researchers wrote. “Instead, it may be more appropriate for clinicians to consider the specific dynamics of the activity, such as velocity and risk of falls from heights. This nuanced perspective can aid in assessing the likelihood of persisting symptoms.” The researchers urged more investigation of this question. “A larger sample with more information on injury height and velocity would be required to confirm whether an association exists.”

In addition, the researchers cited guidelines that include a recommendation for a gradual return to low to moderate physical and cognitive activity starting 24-48 hours after a concussion at a level that does not result in recurrence or exacerbation of symptoms.

“Children do need to return to their lives. They need to return to school,” said Ledoux. “They can have accommodations while they return to school, but just returning to school has huge benefits because you’re reintegrating the child into their typical lifestyle and socialization as well.”

A potential limitation of the study was its reliance on participants who had been seen in emergency departments and thus may have been experiencing more intense symptoms than those seen elsewhere.

The researchers also excluded cases of concussion resulting from assaults and motor vehicle crashes. This decision may explain why they didn’t reproduce the previous observation that patients with SRC tended to recover faster than those with concussions from other causes.

Injuries resulting from assaults and motor vehicle crashes can involve damage beyond concussions, Ledoux said. Including these cases would not allow for an apples-to-apples comparison of SRC and non-SRC.

 

‘Don’t Cocoon Kids’

The authors of an accompanying editorial wrote that the researchers had done “a beautiful job highlighting this important nuance.” Noncontact sports with seemingly little risk “actually carry substantial risks when one imagines the high-impact forces that can occur with a fall from height, albeit rare,” Scott Zuckerman, MD, MPH, assistant professor of neurological surgery at Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues wrote.

The new analysis suggests a need to rethink a “somewhat archaic way of classifying sport risk, which may oversimplify how we categorize risk of brain and spine injuries.”

The commentary also noted how the researchers used the term PSAC to describe lingering symptoms instead of more widely used terms like “persistent postconcussive symptoms” or “postconcussive syndrome.”

“These traditional terms often connote a permanent syndrome or assumption that the concussion itself is solely responsible for 100% of symptoms, which can be harmful to a patient’s recovery,” the editorialists wrote. “Conversely, PSAC offers room for the clinician to discuss how other causes may be maintaining, magnifying, or mimicking concussion symptoms.”

Commenting on the findings, Richard Figler, MD, an orthopedic surgeon at the Cleveland Clinic, Cleveland, praised the researchers for addressing concussion in younger children, a field in which little research has been conducted. The research supports the current approaches to treatment. The approach has shifted toward easing children quickly and safely back into normal routines. “We don’t cocoon kids. We don’t send them to dark rooms,” Figler added.

He also commended the researchers’ decision to examine data about concussions linked to limited contact sports. In contact sports, participants may be more likely to anticipate and prepare for a hit. That’s not the case with injuries sustained in limited contact sports.

“Dodgeball is basically a sucker punch. That’s why these kids have so many concussions,” said Figler. “They typically don’t see the ball coming, or they can’t get out of the way, and they can’t tense themselves to take that blow.”

The Predicting and Preventing Postconcussive Problems in Pediatrics study was funded by the Canadian Institutes of Health Research and the Canadian Institutes of Health Research-Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team. Ledoux reported receiving grants from the Children’s Hospital of Eastern Ontario Foundation, Ontario Brain Institute, and University of Ottawa Brain and Mind Research Institute. She received nonfinancial support from Mobio Interactive outside the submitted work. Zuckerman reported receiving personal fees from the National Football League and Medtronic outside the submitted work. Figler had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Children aged 5-12 years with concussion have similar recovery trajectories, regardless of whether the injury is linked to sports or to other causes, such as falls, new data indicated. 

“With that result, it means we don’t need to change management protocols” depending on the cause of the concussion, study author Andrée-Anne Ledoux, PhD, a scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Ontario, Canada, said in an interview. “That’s kind of good news. We’re applying the right management protocols with them.”

The data were published on December 4 in JAMA Network Open.

 

Secondary Analysis

The results stem from a planned secondary analysis of the prospective Predicting and Preventing Postconcussive Problems in Pediatrics study. Conducted from August 2013 to June 2015 at nine pediatric emergency departments in Canada, it included children of different ages (5 to < 18 years), genders, demographic characteristics, and comorbidities. All participants had a concussion.

The secondary analysis focused on study participants who were aged 5-12 years and had presented within 48 hours of injury. The primary outcome was symptom change, which was defined as current ratings minus preinjury ratings, across time (1, 2, 4, 8, and 12 weeks), measured using the Post-Concussion Symptom Inventory.

No significant differences in postinjury recovery curves were found between participants with sport-related concussions (SRC) and those with non-SRC. The latter injuries resulted from causes such as falls and objects dropped on heads. SRC and non-SRC showed a nonlinear association with time, with symptoms decreasing over time.

Perhaps surprisingly, the researchers also reported a higher rate of persisting symptoms after concussion (PSAC) following limited contact sports than following contact sports such as hockey, soccer, rugby, lacrosse, and football. Limited contact sports include activities such as bicycling, horseback riding, tobogganing, gymnastics, and cheerleading.

This finding suggests that the management of SRC may not require distinct strategies based on sports classification, the researchers wrote. “Instead, it may be more appropriate for clinicians to consider the specific dynamics of the activity, such as velocity and risk of falls from heights. This nuanced perspective can aid in assessing the likelihood of persisting symptoms.” The researchers urged more investigation of this question. “A larger sample with more information on injury height and velocity would be required to confirm whether an association exists.”

In addition, the researchers cited guidelines that include a recommendation for a gradual return to low to moderate physical and cognitive activity starting 24-48 hours after a concussion at a level that does not result in recurrence or exacerbation of symptoms.

“Children do need to return to their lives. They need to return to school,” said Ledoux. “They can have accommodations while they return to school, but just returning to school has huge benefits because you’re reintegrating the child into their typical lifestyle and socialization as well.”

A potential limitation of the study was its reliance on participants who had been seen in emergency departments and thus may have been experiencing more intense symptoms than those seen elsewhere.

The researchers also excluded cases of concussion resulting from assaults and motor vehicle crashes. This decision may explain why they didn’t reproduce the previous observation that patients with SRC tended to recover faster than those with concussions from other causes.

Injuries resulting from assaults and motor vehicle crashes can involve damage beyond concussions, Ledoux said. Including these cases would not allow for an apples-to-apples comparison of SRC and non-SRC.

 

‘Don’t Cocoon Kids’

The authors of an accompanying editorial wrote that the researchers had done “a beautiful job highlighting this important nuance.” Noncontact sports with seemingly little risk “actually carry substantial risks when one imagines the high-impact forces that can occur with a fall from height, albeit rare,” Scott Zuckerman, MD, MPH, assistant professor of neurological surgery at Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues wrote.

The new analysis suggests a need to rethink a “somewhat archaic way of classifying sport risk, which may oversimplify how we categorize risk of brain and spine injuries.”

The commentary also noted how the researchers used the term PSAC to describe lingering symptoms instead of more widely used terms like “persistent postconcussive symptoms” or “postconcussive syndrome.”

“These traditional terms often connote a permanent syndrome or assumption that the concussion itself is solely responsible for 100% of symptoms, which can be harmful to a patient’s recovery,” the editorialists wrote. “Conversely, PSAC offers room for the clinician to discuss how other causes may be maintaining, magnifying, or mimicking concussion symptoms.”

Commenting on the findings, Richard Figler, MD, an orthopedic surgeon at the Cleveland Clinic, Cleveland, praised the researchers for addressing concussion in younger children, a field in which little research has been conducted. The research supports the current approaches to treatment. The approach has shifted toward easing children quickly and safely back into normal routines. “We don’t cocoon kids. We don’t send them to dark rooms,” Figler added.

He also commended the researchers’ decision to examine data about concussions linked to limited contact sports. In contact sports, participants may be more likely to anticipate and prepare for a hit. That’s not the case with injuries sustained in limited contact sports.

“Dodgeball is basically a sucker punch. That’s why these kids have so many concussions,” said Figler. “They typically don’t see the ball coming, or they can’t get out of the way, and they can’t tense themselves to take that blow.”

The Predicting and Preventing Postconcussive Problems in Pediatrics study was funded by the Canadian Institutes of Health Research and the Canadian Institutes of Health Research-Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team. Ledoux reported receiving grants from the Children’s Hospital of Eastern Ontario Foundation, Ontario Brain Institute, and University of Ottawa Brain and Mind Research Institute. She received nonfinancial support from Mobio Interactive outside the submitted work. Zuckerman reported receiving personal fees from the National Football League and Medtronic outside the submitted work. Figler had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Total intravenous anesthesia (TIVA) enables earlier intraoperative monitoring of facial nerve activity than sevoflurane anesthesia during ear surgery, with reduced patient-ventilator dyssynchrony and fewer requirements for postoperative antiemetics.

METHODOLOGY:

• Researchers evaluated the difference in the timeliness of intraoperative monitoring of facial nerve activity during ear surgery with TIVA vs sevoflurane anesthesia.
• They included 98 patients aged 18-74 years undergoing ear surgery between November 2021 and November 2022; patients were randomly assigned to receive either TIVA or sevoflurane during the procedure. Of these, 92 were included in the final analysis.
• Neuromuscular function was monitored quantitatively throughout anesthesia with train-of-four counts and train-of-four ratios.
• The time from the administration of rocuronium to the start of facial nerve monitoring was recorded.
• The primary outcome measure focused on the recovery index, defined as the time interval between a train-of-four ratio of 0.25 and 0.75; the key secondary outcome was the time to reach a train-of-four ratio of 0.25 from rocuronium administration.

TAKEAWAY:

•  
• The time to reach a train-of-four ratio of 0.25 was achieved earlier with TIVA than with sevoflurane (34 minutes vs 51 minutes; P < .001).
• Patient-ventilator dyssynchrony occurred less frequently in the TIVA group than in the sevoflurane group (15% vs 39%; P = .01).
• Postoperative requests for antiemetics were less frequent in the TIVA group than in the sevoflurane group (2% vs 17%; P = .03).

IN PRACTICE:

“We suggest that TIVA may be a better choice than sevoflurane anesthesia to meet an earlier request” for intraoperative facial nerve monitoring by surgeons, the study authors wrote.

SOURCE:

The study was led by Yu Jeong Bang, MD, of the Department of Anesthesiology and Pain Medicine at Sungkyunkwan University School of Medicine, in Seoul, Republic of Korea. It was published online on November 27, 2024, in The Canadian Journal of Anesthesia.

LIMITATIONS:

A careful interpretation of results may be necessary when clinicians use balanced anesthesia, such as sevoflurane with adjuvants like opioids or nonopioids. The feasibility of intraoperative facial nerve monitoring was decided by the surgeon during surgery, and the lowest stimulation intensity threshold for electromyography amplitude was not detected, as it was not the focus of this study. Although patients requiring intraoperative facial nerve monitoring during ear surgery were enrolled, some did not undergo the procedure based on the surgeon’s judgment.

DISCLOSURES:

This study did not receive any funding. The authors disclosed no relevant conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Total intravenous anesthesia (TIVA) enables earlier intraoperative monitoring of facial nerve activity than sevoflurane anesthesia during ear surgery, with reduced patient-ventilator dyssynchrony and fewer requirements for postoperative antiemetics.

METHODOLOGY:

• Researchers evaluated the difference in the timeliness of intraoperative monitoring of facial nerve activity during ear surgery with TIVA vs sevoflurane anesthesia.
• They included 98 patients aged 18-74 years undergoing ear surgery between November 2021 and November 2022; patients were randomly assigned to receive either TIVA or sevoflurane during the procedure. Of these, 92 were included in the final analysis.
• Neuromuscular function was monitored quantitatively throughout anesthesia with train-of-four counts and train-of-four ratios.
• The time from the administration of rocuronium to the start of facial nerve monitoring was recorded.
• The primary outcome measure focused on the recovery index, defined as the time interval between a train-of-four ratio of 0.25 and 0.75; the key secondary outcome was the time to reach a train-of-four ratio of 0.25 from rocuronium administration.

TAKEAWAY:

•  
• The time to reach a train-of-four ratio of 0.25 was achieved earlier with TIVA than with sevoflurane (34 minutes vs 51 minutes; P < .001).
• Patient-ventilator dyssynchrony occurred less frequently in the TIVA group than in the sevoflurane group (15% vs 39%; P = .01).
• Postoperative requests for antiemetics were less frequent in the TIVA group than in the sevoflurane group (2% vs 17%; P = .03).

IN PRACTICE:

“We suggest that TIVA may be a better choice than sevoflurane anesthesia to meet an earlier request” for intraoperative facial nerve monitoring by surgeons, the study authors wrote.

SOURCE:

The study was led by Yu Jeong Bang, MD, of the Department of Anesthesiology and Pain Medicine at Sungkyunkwan University School of Medicine, in Seoul, Republic of Korea. It was published online on November 27, 2024, in The Canadian Journal of Anesthesia.

LIMITATIONS:

A careful interpretation of results may be necessary when clinicians use balanced anesthesia, such as sevoflurane with adjuvants like opioids or nonopioids. The feasibility of intraoperative facial nerve monitoring was decided by the surgeon during surgery, and the lowest stimulation intensity threshold for electromyography amplitude was not detected, as it was not the focus of this study. Although patients requiring intraoperative facial nerve monitoring during ear surgery were enrolled, some did not undergo the procedure based on the surgeon’s judgment.

DISCLOSURES:

This study did not receive any funding. The authors disclosed no relevant conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Total intravenous anesthesia (TIVA) enables earlier intraoperative monitoring of facial nerve activity than sevoflurane anesthesia during ear surgery, with reduced patient-ventilator dyssynchrony and fewer requirements for postoperative antiemetics.

METHODOLOGY:

• Researchers evaluated the difference in the timeliness of intraoperative monitoring of facial nerve activity during ear surgery with TIVA vs sevoflurane anesthesia.
• They included 98 patients aged 18-74 years undergoing ear surgery between November 2021 and November 2022; patients were randomly assigned to receive either TIVA or sevoflurane during the procedure. Of these, 92 were included in the final analysis.
• Neuromuscular function was monitored quantitatively throughout anesthesia with train-of-four counts and train-of-four ratios.
• The time from the administration of rocuronium to the start of facial nerve monitoring was recorded.
• The primary outcome measure focused on the recovery index, defined as the time interval between a train-of-four ratio of 0.25 and 0.75; the key secondary outcome was the time to reach a train-of-four ratio of 0.25 from rocuronium administration.

TAKEAWAY:

•  
• The time to reach a train-of-four ratio of 0.25 was achieved earlier with TIVA than with sevoflurane (34 minutes vs 51 minutes; P < .001).
• Patient-ventilator dyssynchrony occurred less frequently in the TIVA group than in the sevoflurane group (15% vs 39%; P = .01).
• Postoperative requests for antiemetics were less frequent in the TIVA group than in the sevoflurane group (2% vs 17%; P = .03).

IN PRACTICE:

“We suggest that TIVA may be a better choice than sevoflurane anesthesia to meet an earlier request” for intraoperative facial nerve monitoring by surgeons, the study authors wrote.

SOURCE:

The study was led by Yu Jeong Bang, MD, of the Department of Anesthesiology and Pain Medicine at Sungkyunkwan University School of Medicine, in Seoul, Republic of Korea. It was published online on November 27, 2024, in The Canadian Journal of Anesthesia.

LIMITATIONS:

A careful interpretation of results may be necessary when clinicians use balanced anesthesia, such as sevoflurane with adjuvants like opioids or nonopioids. The feasibility of intraoperative facial nerve monitoring was decided by the surgeon during surgery, and the lowest stimulation intensity threshold for electromyography amplitude was not detected, as it was not the focus of this study. Although patients requiring intraoperative facial nerve monitoring during ear surgery were enrolled, some did not undergo the procedure based on the surgeon’s judgment.

DISCLOSURES:

This study did not receive any funding. The authors disclosed no relevant conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

In preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.