Neurology

Cervical manipulations have been associated with vascular complications. While the incidence of carotid dissections does not seem to have increased, the question remains open for vertebral artery injuries. We must remain vigilant!

Resorting to joint manipulation for neck pain is not unusual. Currently, cervical manipulation remains a popular first-line treatment for cervicodynia or headaches. Although evidence exists showing that specific joint mobilization can improve this type of symptomatology, there is a possibility that it may risk damaging the cervical arteries and causing ischemic stroke through arterial dissection.

Epidemiologically, internal carotid artery dissection is a relatively rare event with an estimated annual incidence of 1.72 per 100,000 individuals (those most likely to be diagnosed being obviously those leading to hospitalization for stroke) but represents one of the most common causes of stroke in young and middle-aged adults. Faced with case reports that may raise concerns and hypotheses about an associated risk, two studies have sought to delve into the issue.
 

No Increased Carotid Risk Identified

The first study, of a case-cross design, identified all incident cases of ischemic stroke in the territory of the internal carotid artery admitted to the hospital over a 9-year period using administrative healthcare data, the cases being used as their own control by sampling control periods before the date of the index stroke. Thus, 15,523 cases were compared with 62,092 control periods using exposure windows of 1, 3, 7, and 14 days before the stroke. The study also compared post-medical consultation and post-chiropractic consultation outcomes, knowing that as a first-line for complaints of neck pain or headache, patients often turn to one of these two types of primary care clinicians.

However, data analysis shows, among subjects aged under 45 years, positive associations for both different consultations in cases of subsequent carotid stroke (but no association for those aged over 45 years). These associations tended to increase when analyses were limited to visits for diagnoses of neck pain and headaches. Nevertheless, there was no significant difference between risk estimates after chiropractic or general medical consultation.

A notable limitation of this work is that it did not focus on strokes due to vertebral artery dissections that run through the transverse foramina of the cervical vertebrae.
 

A Screening Test Lacking Precision

More recently, the International Federation of Orthopedic Manual Physical Therapists has looked into the subject to refine the assessment of the risk for vascular complications in patients seeking physiotherapy/osteopathy care for neck pain and/or headaches. Through a cross-sectional study involving 150 patients, it tested a vascular complication risk index (from high to low grade, based on history taking and clinical examination), developed to estimate the risk for the presence of vascular rather than musculoskeletal pathology, to determine whether or not there is a contraindication to cervical manipulation.

However, the developed index had only low sensitivity (0.50; 95% CI, 0.39-0.61) and moderate specificity (0.63; 95% CI, 0.51-0.75), knowing that the reference test was a consensus medical decision made by a vascular neurologist, an interventional neurologist, and a neuroradiologist (based on clinical data and cervical MRI). Similarly, positive and negative likelihood ratios were low at 1.36 (95% CI, 0.93-1.99) and 0.79 (95% CI, 0.60-1.05), respectively.

In conclusion, the data from the case-cross study did not seem to demonstrate an excess risk for stroke in the territory of the internal carotid artery after cervical joint manipulations. Associations between cervical manipulation sessions or medical consultations and carotid strokes appear similar and could have been due to the fact that patients with early symptoms related to arterial dissection seek care before developing their stroke.

However, it is regrettable that the study did not focus on vertebral artery dissections, which are anatomically more exposed to cervical chiropractic sessions. Nevertheless, because indices defined from joint tests and medical history are insufficient to identify patients “at risk or in the process of arterial dissection,” and because stroke can result in severe disability, practitioners managing patients with neck pain cannot take this type of complication lightly.

This story was translated from JIM 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.

Cervical manipulations have been associated with vascular complications. While the incidence of carotid dissections does not seem to have increased, the question remains open for vertebral artery injuries. We must remain vigilant!

Resorting to joint manipulation for neck pain is not unusual. Currently, cervical manipulation remains a popular first-line treatment for cervicodynia or headaches. Although evidence exists showing that specific joint mobilization can improve this type of symptomatology, there is a possibility that it may risk damaging the cervical arteries and causing ischemic stroke through arterial dissection.

Epidemiologically, internal carotid artery dissection is a relatively rare event with an estimated annual incidence of 1.72 per 100,000 individuals (those most likely to be diagnosed being obviously those leading to hospitalization for stroke) but represents one of the most common causes of stroke in young and middle-aged adults. Faced with case reports that may raise concerns and hypotheses about an associated risk, two studies have sought to delve into the issue.
 

No Increased Carotid Risk Identified

The first study, of a case-cross design, identified all incident cases of ischemic stroke in the territory of the internal carotid artery admitted to the hospital over a 9-year period using administrative healthcare data, the cases being used as their own control by sampling control periods before the date of the index stroke. Thus, 15,523 cases were compared with 62,092 control periods using exposure windows of 1, 3, 7, and 14 days before the stroke. The study also compared post-medical consultation and post-chiropractic consultation outcomes, knowing that as a first-line for complaints of neck pain or headache, patients often turn to one of these two types of primary care clinicians.

However, data analysis shows, among subjects aged under 45 years, positive associations for both different consultations in cases of subsequent carotid stroke (but no association for those aged over 45 years). These associations tended to increase when analyses were limited to visits for diagnoses of neck pain and headaches. Nevertheless, there was no significant difference between risk estimates after chiropractic or general medical consultation.

A notable limitation of this work is that it did not focus on strokes due to vertebral artery dissections that run through the transverse foramina of the cervical vertebrae.
 

A Screening Test Lacking Precision

More recently, the International Federation of Orthopedic Manual Physical Therapists has looked into the subject to refine the assessment of the risk for vascular complications in patients seeking physiotherapy/osteopathy care for neck pain and/or headaches. Through a cross-sectional study involving 150 patients, it tested a vascular complication risk index (from high to low grade, based on history taking and clinical examination), developed to estimate the risk for the presence of vascular rather than musculoskeletal pathology, to determine whether or not there is a contraindication to cervical manipulation.

However, the developed index had only low sensitivity (0.50; 95% CI, 0.39-0.61) and moderate specificity (0.63; 95% CI, 0.51-0.75), knowing that the reference test was a consensus medical decision made by a vascular neurologist, an interventional neurologist, and a neuroradiologist (based on clinical data and cervical MRI). Similarly, positive and negative likelihood ratios were low at 1.36 (95% CI, 0.93-1.99) and 0.79 (95% CI, 0.60-1.05), respectively.

In conclusion, the data from the case-cross study did not seem to demonstrate an excess risk for stroke in the territory of the internal carotid artery after cervical joint manipulations. Associations between cervical manipulation sessions or medical consultations and carotid strokes appear similar and could have been due to the fact that patients with early symptoms related to arterial dissection seek care before developing their stroke.

However, it is regrettable that the study did not focus on vertebral artery dissections, which are anatomically more exposed to cervical chiropractic sessions. Nevertheless, because indices defined from joint tests and medical history are insufficient to identify patients “at risk or in the process of arterial dissection,” and because stroke can result in severe disability, practitioners managing patients with neck pain cannot take this type of complication lightly.

This story was translated from JIM 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.

Cervical manipulations have been associated with vascular complications. While the incidence of carotid dissections does not seem to have increased, the question remains open for vertebral artery injuries. We must remain vigilant!

Resorting to joint manipulation for neck pain is not unusual. Currently, cervical manipulation remains a popular first-line treatment for cervicodynia or headaches. Although evidence exists showing that specific joint mobilization can improve this type of symptomatology, there is a possibility that it may risk damaging the cervical arteries and causing ischemic stroke through arterial dissection.

Epidemiologically, internal carotid artery dissection is a relatively rare event with an estimated annual incidence of 1.72 per 100,000 individuals (those most likely to be diagnosed being obviously those leading to hospitalization for stroke) but represents one of the most common causes of stroke in young and middle-aged adults. Faced with case reports that may raise concerns and hypotheses about an associated risk, two studies have sought to delve into the issue.
 

No Increased Carotid Risk Identified

The first study, of a case-cross design, identified all incident cases of ischemic stroke in the territory of the internal carotid artery admitted to the hospital over a 9-year period using administrative healthcare data, the cases being used as their own control by sampling control periods before the date of the index stroke. Thus, 15,523 cases were compared with 62,092 control periods using exposure windows of 1, 3, 7, and 14 days before the stroke. The study also compared post-medical consultation and post-chiropractic consultation outcomes, knowing that as a first-line for complaints of neck pain or headache, patients often turn to one of these two types of primary care clinicians.

However, data analysis shows, among subjects aged under 45 years, positive associations for both different consultations in cases of subsequent carotid stroke (but no association for those aged over 45 years). These associations tended to increase when analyses were limited to visits for diagnoses of neck pain and headaches. Nevertheless, there was no significant difference between risk estimates after chiropractic or general medical consultation.

A notable limitation of this work is that it did not focus on strokes due to vertebral artery dissections that run through the transverse foramina of the cervical vertebrae.
 

A Screening Test Lacking Precision

More recently, the International Federation of Orthopedic Manual Physical Therapists has looked into the subject to refine the assessment of the risk for vascular complications in patients seeking physiotherapy/osteopathy care for neck pain and/or headaches. Through a cross-sectional study involving 150 patients, it tested a vascular complication risk index (from high to low grade, based on history taking and clinical examination), developed to estimate the risk for the presence of vascular rather than musculoskeletal pathology, to determine whether or not there is a contraindication to cervical manipulation.

However, the developed index had only low sensitivity (0.50; 95% CI, 0.39-0.61) and moderate specificity (0.63; 95% CI, 0.51-0.75), knowing that the reference test was a consensus medical decision made by a vascular neurologist, an interventional neurologist, and a neuroradiologist (based on clinical data and cervical MRI). Similarly, positive and negative likelihood ratios were low at 1.36 (95% CI, 0.93-1.99) and 0.79 (95% CI, 0.60-1.05), respectively.

In conclusion, the data from the case-cross study did not seem to demonstrate an excess risk for stroke in the territory of the internal carotid artery after cervical joint manipulations. Associations between cervical manipulation sessions or medical consultations and carotid strokes appear similar and could have been due to the fact that patients with early symptoms related to arterial dissection seek care before developing their stroke.

However, it is regrettable that the study did not focus on vertebral artery dissections, which are anatomically more exposed to cervical chiropractic sessions. Nevertheless, because indices defined from joint tests and medical history are insufficient to identify patients “at risk or in the process of arterial dissection,” and because stroke can result in severe disability, practitioners managing patients with neck pain cannot take this type of complication lightly.

This story was translated from JIM 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:

New research shows increased screen time in children aged 12-36 months is associated with reduced verbal interactions between toddlers and their parents, which in turn could affect language development. 

METHODOLOGY:

• The study included data from 220 families in Australia.
• Researchers used advanced speech recognition technology to capture children’s screen time and language environment at home during a 16-hour window every 6 months.
• They adjusted for variables such as the sex of the child, the education level of the mother, and psychological distress in the primary caregiver.

TAKEAWAY: 

• Increases in screen time were associated with decreases in words spoken near children by adults, vocalizations by children, and back-and-forth interactions between adults and children. This correlation was especially notable at age 36 months.
• At age 36 months, each additional minute of screen time was linked to children hearing 6.6 fewer adult words, making 4.9 fewer vocalizations, and participating in 1.1 fewer conversational interactions.
• Based on the average daily screen time at that age seen in the study — 172 minutes (2.87 hours) — “children could be missing out on 1139 adult words, 843 vocalizations, and 194 conversational turns per day,” the researchers estimated.

IN PRACTICE:

“Identifying different ways that screen time could facilitate parent-child interactions, such as through interactive co-viewing, may be important strategies to support families given the current ubiquitous nature of screen time in families’ lives,” the authors of the study wrote.

What children watch and listen to may be an important consideration, according to a developmental scientist who was not involved with the study.

“It could be that less communicative contact with the caregiver is not as detrimental if the screen time is of high quality and developmentally appropriate, educational content,” Marina Bazhydai, PhD, with Lancaster University in Lancaster, United Kingdom, said in her comments on the research. 

SOURCE:

Mary E. Brushe, PhD, with Telethon Kids Institute and the University of Western Australia in Adelaide, was the corresponding author of the study. The research was published online in JAMA Pediatrics.

LIMITATIONS:

The study’s reliance on speech recognition technology did not capture all nuances of screen exposure.

DISCLOSURES:

This study was supported by grants from the Australian National Health and Medical Research Council.

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:

New research shows increased screen time in children aged 12-36 months is associated with reduced verbal interactions between toddlers and their parents, which in turn could affect language development. 

METHODOLOGY:

• The study included data from 220 families in Australia.
• Researchers used advanced speech recognition technology to capture children’s screen time and language environment at home during a 16-hour window every 6 months.
• They adjusted for variables such as the sex of the child, the education level of the mother, and psychological distress in the primary caregiver.

TAKEAWAY: 

• Increases in screen time were associated with decreases in words spoken near children by adults, vocalizations by children, and back-and-forth interactions between adults and children. This correlation was especially notable at age 36 months.
• At age 36 months, each additional minute of screen time was linked to children hearing 6.6 fewer adult words, making 4.9 fewer vocalizations, and participating in 1.1 fewer conversational interactions.
• Based on the average daily screen time at that age seen in the study — 172 minutes (2.87 hours) — “children could be missing out on 1139 adult words, 843 vocalizations, and 194 conversational turns per day,” the researchers estimated.

IN PRACTICE:

“Identifying different ways that screen time could facilitate parent-child interactions, such as through interactive co-viewing, may be important strategies to support families given the current ubiquitous nature of screen time in families’ lives,” the authors of the study wrote.

What children watch and listen to may be an important consideration, according to a developmental scientist who was not involved with the study.

“It could be that less communicative contact with the caregiver is not as detrimental if the screen time is of high quality and developmentally appropriate, educational content,” Marina Bazhydai, PhD, with Lancaster University in Lancaster, United Kingdom, said in her comments on the research. 

SOURCE:

Mary E. Brushe, PhD, with Telethon Kids Institute and the University of Western Australia in Adelaide, was the corresponding author of the study. The research was published online in JAMA Pediatrics.

LIMITATIONS:

The study’s reliance on speech recognition technology did not capture all nuances of screen exposure.

DISCLOSURES:

This study was supported by grants from the Australian National Health and Medical Research Council.

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:

New research shows increased screen time in children aged 12-36 months is associated with reduced verbal interactions between toddlers and their parents, which in turn could affect language development. 

METHODOLOGY:

• The study included data from 220 families in Australia.
• Researchers used advanced speech recognition technology to capture children’s screen time and language environment at home during a 16-hour window every 6 months.
• They adjusted for variables such as the sex of the child, the education level of the mother, and psychological distress in the primary caregiver.

TAKEAWAY: 

• Increases in screen time were associated with decreases in words spoken near children by adults, vocalizations by children, and back-and-forth interactions between adults and children. This correlation was especially notable at age 36 months.
• At age 36 months, each additional minute of screen time was linked to children hearing 6.6 fewer adult words, making 4.9 fewer vocalizations, and participating in 1.1 fewer conversational interactions.
• Based on the average daily screen time at that age seen in the study — 172 minutes (2.87 hours) — “children could be missing out on 1139 adult words, 843 vocalizations, and 194 conversational turns per day,” the researchers estimated.

IN PRACTICE:

“Identifying different ways that screen time could facilitate parent-child interactions, such as through interactive co-viewing, may be important strategies to support families given the current ubiquitous nature of screen time in families’ lives,” the authors of the study wrote.

What children watch and listen to may be an important consideration, according to a developmental scientist who was not involved with the study.

“It could be that less communicative contact with the caregiver is not as detrimental if the screen time is of high quality and developmentally appropriate, educational content,” Marina Bazhydai, PhD, with Lancaster University in Lancaster, United Kingdom, said in her comments on the research. 

SOURCE:

Mary E. Brushe, PhD, with Telethon Kids Institute and the University of Western Australia in Adelaide, was the corresponding author of the study. The research was published online in JAMA Pediatrics.

LIMITATIONS:

The study’s reliance on speech recognition technology did not capture all nuances of screen exposure.

DISCLOSURES:

This study was supported by grants from the Australian National Health and Medical Research Council.

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.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Epilepsy was linked to a significantly increased the risk for hospitalization and death from COVID-19 early in the pandemic, while healthcare utilization rates in this patient population declined, data from two linked studies showed. 

Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%. 

“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.

The findings were published online March 5 in Epilepsia. 
 

Skill Shifting 

Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.

During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.

To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.

Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy. 

The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.

Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37). 

After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001). 

The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.

Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants. 
 

Consultations Canceled 

In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic. 

In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls. 

However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)

The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted. 

“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.

Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.

A version of this article appeared on Medscape.com .

Epilepsy was linked to a significantly increased the risk for hospitalization and death from COVID-19 early in the pandemic, while healthcare utilization rates in this patient population declined, data from two linked studies showed. 

Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%. 

“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.

The findings were published online March 5 in Epilepsia. 
 

Skill Shifting 

Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.

During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.

To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.

Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy. 

The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.

Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37). 

After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001). 

The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.

Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants. 
 

Consultations Canceled 

In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic. 

In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls. 

However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)

The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted. 

“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.

Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.

A version of this article appeared on Medscape.com .

Epilepsy was linked to a significantly increased the risk for hospitalization and death from COVID-19 early in the pandemic, while healthcare utilization rates in this patient population declined, data from two linked studies showed. 

Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%. 

“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.

The findings were published online March 5 in Epilepsia. 
 

Skill Shifting 

Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.

During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.

To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.

Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy. 

The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.

Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37). 

After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001). 

The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.

Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants. 
 

Consultations Canceled 

In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic. 

In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls. 

However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)

The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted. 

“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.

Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.

A version of this article appeared on Medscape.com .

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.

They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.

Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.

“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.

However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
 

Varying Definitions

The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”

Dr. Hallett offers his own definition of FND, which includes the following characteristics:

• A neurological disorder, characterized by almost any type of neurological symptom
• Not voluntarily produced
• Caused by a brain network dysfunction that does not exclude the possibility of normal function
• Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
• Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.

The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.

Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.

Women comprise between 60% and 75% of the population with FNDs.
 

Diagnosis

FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.

She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.

For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.

Massachusetts General Hospital

Functional seizures

A definitive diagnosis can depend on the type of disorder.

“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.

There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.

Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.

Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
 

Functional movement disorders

Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.

For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.

One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.

When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.

“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
 

Treatment

In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.

“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.

Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.

“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.

This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.

They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.

Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.

“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.

However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
 

Varying Definitions

The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”

Dr. Hallett offers his own definition of FND, which includes the following characteristics:

• A neurological disorder, characterized by almost any type of neurological symptom
• Not voluntarily produced
• Caused by a brain network dysfunction that does not exclude the possibility of normal function
• Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
• Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.

The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.

Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.

Women comprise between 60% and 75% of the population with FNDs.
 

Diagnosis

FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.

She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.

For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.

Massachusetts General Hospital

Functional seizures

A definitive diagnosis can depend on the type of disorder.

“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.

There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.

Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.

Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
 

Functional movement disorders

Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.

For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.

One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.

When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.

“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
 

Treatment

In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.

“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.

Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.

“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.

This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.

They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.

Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.

“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.

However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
 

Varying Definitions

The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”

Dr. Hallett offers his own definition of FND, which includes the following characteristics:

• A neurological disorder, characterized by almost any type of neurological symptom
• Not voluntarily produced
• Caused by a brain network dysfunction that does not exclude the possibility of normal function
• Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
• Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.

The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.

Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.

Women comprise between 60% and 75% of the population with FNDs.
 

Diagnosis

FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.

She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.

For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.

Massachusetts General Hospital

Functional seizures

A definitive diagnosis can depend on the type of disorder.

“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.

There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.

Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.

Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
 

Functional movement disorders

Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.

For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.

One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.

When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.

“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
 

Treatment

In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.

“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.

Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.

“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.

This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.

A new study from the United Kingdom provides greater clarity on how SARS-CoV-2 infection can affect cognition and memory, including novel data on how long brain fog may last after the illness resolves and which cognitive functions are most vulnerable. 

In a large community sample, researchers found that on average, people who had recovered from COVID-19 showed small cognitive deficits equivalent to a 3-point loss in IQ for up to 1 year or more after recovering from the acute illness compared with peers who never had COVID-19.

However, people who had more severe cases, requiring treatment in a hospital intensive care unit, had cognitive deficits equivalent to a 9-point drop in IQ.

“People with ongoing persistent symptoms, indicative of long COVID, had larger cognitive deficits than people whose symptoms had resolved,” first author Adam Hampshire, PhD, with Imperial College London, London, England, told this news organization. 

The largest deficits among cognitive tasks were in memory, reasoning, and executive function, he added.

“That is, people who had had COVID-19 were both slower and less accurate when performing tasks that measure those abilities,” Dr. Hampshire said. “The group with the largest cognitive deficits were patients who had been in intensive care for COVID-19.”

The study was published online in The New England Journal of Medicine. 
 

Lingering Brain Fog

Cognitive symptoms after SARS-CoV-2 infection are well recognized, but whether objectively measurable cognitive deficits exist and how long they persist remains unclear. 

To investigate, researchers invited 800,000 adults from the REACT study of SARS-CoV-2 transmission in England to complete an online assessment for cognitive function with eight domains.

Altogether, 141,583 participants started the cognitive battery by completing at least one task, and 112,964 completed all eight tasks.

The researchers estimated global cognitive scores among participants who had been previously infected with SARS-CoV-2 with symptoms that persisted for at least 12 weeks, whether or not resolved, and among uninfected participants. 

Compared with uninfected adults, those who had COVID-19 that resolved had a small cognitive deficit, corresponding to a 3-point loss in IQ, the researchers found. 

Adults with unresolved persistent COVID-19 symptoms had the equivalent of a 6-point loss in IQ, and those who had been admitted to the intensive care unit had the equivalent of a 9-point loss in IQ, in line with previous findings of cognitive deficits in patients hospitalized in a critical care unit, the researchers report. 

Larger cognitive deficits were evident in adults infected early in the pandemic by the original SARS-CoV-2 virus or the B.1.1.7 variant, whereas peers infected later in the pandemic (eg., in the Omicron period), showed smaller cognitive deficits. This finding is in line with other studies suggesting that the association between COVID-19–associated cognitive deficits attenuated as the pandemic progressed, the researchers noted. 

They also found that people who had COVID-19 after receiving two or more vaccinations showed better cognitive performance compared with those who had not been vaccinated. 

The memory, reasoning, and executive function tasks were among the most sensitive to COVID-19–related cognitive differences and performance on these tasks differed according to illness duration and hospitalization. 

Dr. Hampshire said that more research is needed to determine whether the cognitive deficits resolve with time. 

“The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance,” he said.

 

Larger Cognitive Deficits Likely?

These results are “a concern and the broader implications require evaluation,” wrote Ziyad Al-Aly, MD, with Washington University School of Medicine in St. Louis, Missouri, and Clifford Rosen, MD, with Tufts University School of Medicine in Boston, Massachusetts, in an accompanying editorial. 

In their view, several outstanding questions remain, including what the potential functional implications of a 3-point loss in IQ may be and whether COVID-19–related cognitive deficits predispose to a higher risk for dementia later in life. 

“A deeper understanding of the biology of cognitive dysfunction after SARS-CoV-2 infection and how best to prevent and treat it are critical for addressing the needs of affected persons and preserving the cognitive health of populations,” Drs. Al-Aly and Rosen concluded. 

Commenting on the study for this news organization, Jacqueline Becker, PhD, clinical neuropsychologist and assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York City, noted that “one important caveat” is that the study used an online assessment tool for cognitive function and therefore the findings should be taken with “a grain of salt.”

“That said, this is a large sample, and the findings are generally consistent with what we’ve seen in terms of cognitive deficits post-COVID,” Dr. Becker said. 

It’s likely that this study “underestimates” the degree of cognitive deficits that would be seen on validated neuropsychological tests, she added.

In a recent study, Dr. Becker and her colleagues investigated rates of cognitive impairment in 740 COVID-19 patients who recovered and were treated in outpatient, emergency department, or inpatient hospital settings. 

Using validated neuropsychological measures, they found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were predominant among hospitalized patients. 

Dr. Becker noted that in her experience, cognition typically will improve in some patients 12-18 months post COVID. 

Support for the study was provided by the National Institute for Health and Care Research and UK Research and Innovation and by the Department of Health and Social Care in England and the Huo Family Foundation. Disclosures for authors and editorial writers are available at NEJM.org. Dr. Becker has no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study from the United Kingdom provides greater clarity on how SARS-CoV-2 infection can affect cognition and memory, including novel data on how long brain fog may last after the illness resolves and which cognitive functions are most vulnerable. 

In a large community sample, researchers found that on average, people who had recovered from COVID-19 showed small cognitive deficits equivalent to a 3-point loss in IQ for up to 1 year or more after recovering from the acute illness compared with peers who never had COVID-19.

However, people who had more severe cases, requiring treatment in a hospital intensive care unit, had cognitive deficits equivalent to a 9-point drop in IQ.

“People with ongoing persistent symptoms, indicative of long COVID, had larger cognitive deficits than people whose symptoms had resolved,” first author Adam Hampshire, PhD, with Imperial College London, London, England, told this news organization. 

The largest deficits among cognitive tasks were in memory, reasoning, and executive function, he added.

“That is, people who had had COVID-19 were both slower and less accurate when performing tasks that measure those abilities,” Dr. Hampshire said. “The group with the largest cognitive deficits were patients who had been in intensive care for COVID-19.”

The study was published online in The New England Journal of Medicine. 
 

Lingering Brain Fog

Cognitive symptoms after SARS-CoV-2 infection are well recognized, but whether objectively measurable cognitive deficits exist and how long they persist remains unclear. 

To investigate, researchers invited 800,000 adults from the REACT study of SARS-CoV-2 transmission in England to complete an online assessment for cognitive function with eight domains.

Altogether, 141,583 participants started the cognitive battery by completing at least one task, and 112,964 completed all eight tasks.

The researchers estimated global cognitive scores among participants who had been previously infected with SARS-CoV-2 with symptoms that persisted for at least 12 weeks, whether or not resolved, and among uninfected participants. 

Compared with uninfected adults, those who had COVID-19 that resolved had a small cognitive deficit, corresponding to a 3-point loss in IQ, the researchers found. 

Adults with unresolved persistent COVID-19 symptoms had the equivalent of a 6-point loss in IQ, and those who had been admitted to the intensive care unit had the equivalent of a 9-point loss in IQ, in line with previous findings of cognitive deficits in patients hospitalized in a critical care unit, the researchers report. 

Larger cognitive deficits were evident in adults infected early in the pandemic by the original SARS-CoV-2 virus or the B.1.1.7 variant, whereas peers infected later in the pandemic (eg., in the Omicron period), showed smaller cognitive deficits. This finding is in line with other studies suggesting that the association between COVID-19–associated cognitive deficits attenuated as the pandemic progressed, the researchers noted. 

They also found that people who had COVID-19 after receiving two or more vaccinations showed better cognitive performance compared with those who had not been vaccinated. 

The memory, reasoning, and executive function tasks were among the most sensitive to COVID-19–related cognitive differences and performance on these tasks differed according to illness duration and hospitalization. 

Dr. Hampshire said that more research is needed to determine whether the cognitive deficits resolve with time. 

“The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance,” he said.

 

Larger Cognitive Deficits Likely?

These results are “a concern and the broader implications require evaluation,” wrote Ziyad Al-Aly, MD, with Washington University School of Medicine in St. Louis, Missouri, and Clifford Rosen, MD, with Tufts University School of Medicine in Boston, Massachusetts, in an accompanying editorial. 

In their view, several outstanding questions remain, including what the potential functional implications of a 3-point loss in IQ may be and whether COVID-19–related cognitive deficits predispose to a higher risk for dementia later in life. 

“A deeper understanding of the biology of cognitive dysfunction after SARS-CoV-2 infection and how best to prevent and treat it are critical for addressing the needs of affected persons and preserving the cognitive health of populations,” Drs. Al-Aly and Rosen concluded. 

Commenting on the study for this news organization, Jacqueline Becker, PhD, clinical neuropsychologist and assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York City, noted that “one important caveat” is that the study used an online assessment tool for cognitive function and therefore the findings should be taken with “a grain of salt.”

“That said, this is a large sample, and the findings are generally consistent with what we’ve seen in terms of cognitive deficits post-COVID,” Dr. Becker said. 

It’s likely that this study “underestimates” the degree of cognitive deficits that would be seen on validated neuropsychological tests, she added.

In a recent study, Dr. Becker and her colleagues investigated rates of cognitive impairment in 740 COVID-19 patients who recovered and were treated in outpatient, emergency department, or inpatient hospital settings. 

Using validated neuropsychological measures, they found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were predominant among hospitalized patients. 

Dr. Becker noted that in her experience, cognition typically will improve in some patients 12-18 months post COVID. 

Support for the study was provided by the National Institute for Health and Care Research and UK Research and Innovation and by the Department of Health and Social Care in England and the Huo Family Foundation. Disclosures for authors and editorial writers are available at NEJM.org. Dr. Becker has no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study from the United Kingdom provides greater clarity on how SARS-CoV-2 infection can affect cognition and memory, including novel data on how long brain fog may last after the illness resolves and which cognitive functions are most vulnerable. 

In a large community sample, researchers found that on average, people who had recovered from COVID-19 showed small cognitive deficits equivalent to a 3-point loss in IQ for up to 1 year or more after recovering from the acute illness compared with peers who never had COVID-19.

However, people who had more severe cases, requiring treatment in a hospital intensive care unit, had cognitive deficits equivalent to a 9-point drop in IQ.

“People with ongoing persistent symptoms, indicative of long COVID, had larger cognitive deficits than people whose symptoms had resolved,” first author Adam Hampshire, PhD, with Imperial College London, London, England, told this news organization. 

The largest deficits among cognitive tasks were in memory, reasoning, and executive function, he added.

“That is, people who had had COVID-19 were both slower and less accurate when performing tasks that measure those abilities,” Dr. Hampshire said. “The group with the largest cognitive deficits were patients who had been in intensive care for COVID-19.”

The study was published online in The New England Journal of Medicine. 
 

Lingering Brain Fog

Cognitive symptoms after SARS-CoV-2 infection are well recognized, but whether objectively measurable cognitive deficits exist and how long they persist remains unclear. 

To investigate, researchers invited 800,000 adults from the REACT study of SARS-CoV-2 transmission in England to complete an online assessment for cognitive function with eight domains.

Altogether, 141,583 participants started the cognitive battery by completing at least one task, and 112,964 completed all eight tasks.

The researchers estimated global cognitive scores among participants who had been previously infected with SARS-CoV-2 with symptoms that persisted for at least 12 weeks, whether or not resolved, and among uninfected participants. 

Compared with uninfected adults, those who had COVID-19 that resolved had a small cognitive deficit, corresponding to a 3-point loss in IQ, the researchers found. 

Adults with unresolved persistent COVID-19 symptoms had the equivalent of a 6-point loss in IQ, and those who had been admitted to the intensive care unit had the equivalent of a 9-point loss in IQ, in line with previous findings of cognitive deficits in patients hospitalized in a critical care unit, the researchers report. 

Larger cognitive deficits were evident in adults infected early in the pandemic by the original SARS-CoV-2 virus or the B.1.1.7 variant, whereas peers infected later in the pandemic (eg., in the Omicron period), showed smaller cognitive deficits. This finding is in line with other studies suggesting that the association between COVID-19–associated cognitive deficits attenuated as the pandemic progressed, the researchers noted. 

They also found that people who had COVID-19 after receiving two or more vaccinations showed better cognitive performance compared with those who had not been vaccinated. 

The memory, reasoning, and executive function tasks were among the most sensitive to COVID-19–related cognitive differences and performance on these tasks differed according to illness duration and hospitalization. 

Dr. Hampshire said that more research is needed to determine whether the cognitive deficits resolve with time. 

“The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance,” he said.

 

Larger Cognitive Deficits Likely?

These results are “a concern and the broader implications require evaluation,” wrote Ziyad Al-Aly, MD, with Washington University School of Medicine in St. Louis, Missouri, and Clifford Rosen, MD, with Tufts University School of Medicine in Boston, Massachusetts, in an accompanying editorial. 

In their view, several outstanding questions remain, including what the potential functional implications of a 3-point loss in IQ may be and whether COVID-19–related cognitive deficits predispose to a higher risk for dementia later in life. 

“A deeper understanding of the biology of cognitive dysfunction after SARS-CoV-2 infection and how best to prevent and treat it are critical for addressing the needs of affected persons and preserving the cognitive health of populations,” Drs. Al-Aly and Rosen concluded. 

Commenting on the study for this news organization, Jacqueline Becker, PhD, clinical neuropsychologist and assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York City, noted that “one important caveat” is that the study used an online assessment tool for cognitive function and therefore the findings should be taken with “a grain of salt.”

“That said, this is a large sample, and the findings are generally consistent with what we’ve seen in terms of cognitive deficits post-COVID,” Dr. Becker said. 

It’s likely that this study “underestimates” the degree of cognitive deficits that would be seen on validated neuropsychological tests, she added.

In a recent study, Dr. Becker and her colleagues investigated rates of cognitive impairment in 740 COVID-19 patients who recovered and were treated in outpatient, emergency department, or inpatient hospital settings. 

Using validated neuropsychological measures, they found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were predominant among hospitalized patients. 

Dr. Becker noted that in her experience, cognition typically will improve in some patients 12-18 months post COVID. 

Support for the study was provided by the National Institute for Health and Care Research and UK Research and Innovation and by the Department of Health and Social Care in England and the Huo Family Foundation. Disclosures for authors and editorial writers are available at NEJM.org. Dr. Becker has no relevant disclosures.

A version of this article appeared on Medscape.com.

Medtronic Neurosurgery has recalled Duet External Drainage and Monitoring System (EDMS) catheter tubing because the catheter may disconnect from the patient line stopcock connectors.

If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.

The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue. 

The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.

The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.

Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products. 

Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free. 

If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique. 

It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.

Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.

A version of this article appeared on Medscape.com.

Medtronic Neurosurgery has recalled Duet External Drainage and Monitoring System (EDMS) catheter tubing because the catheter may disconnect from the patient line stopcock connectors.

If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.

The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue. 

The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.

The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.

Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products. 

Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free. 

If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique. 

It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.

Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.

A version of this article appeared on Medscape.com.

Medtronic Neurosurgery has recalled Duet External Drainage and Monitoring System (EDMS) catheter tubing because the catheter may disconnect from the patient line stopcock connectors.

If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.

The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue. 

The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.

The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.

Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products. 

Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free. 

If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique. 

It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.

Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.

A version of this article appeared on Medscape.com.

Alzheimer’s research is plagued with misconduct and fraud, undermining the progress toward understanding and treating the disease, say investigators who endeavor to expose errors and misleading practices.

The book is yet to be closed, for instance, on whether a 2006 paper by Sylvain Lesne positing amyloid as a major cause of Alzheimer’s was based on fraudulent data. Suspicions about the paper were first raised in late 2021 by Matthew Schrag, MD, PhD, an assistant professor of neurology at Vanderbilt University Medical Center, Nashville, Tennessee.

Dr. Schrag also queried the work of a City University of New York (CUNY) researcher who proposed PT-125 (now simufilam) as a potential anti-amyloid for Alzheimer’s disease. Even though CUNY recently found “egregious” and potentially deliberate misconduct by that researcher, Cassava Sciences is continuing phase 3 trials of simufilam.

Now questions are being raised about work from the lab of Berislav V. Zlokovic, PhD, a prominent neuroscientist at the University of Southern California (USC), Los Angeles, California, and also about studies conducted under the aegis of Domenico Pratico, MD, the director of the Alzheimer’s Center at Temple University in Philadelphia, Pennsylvania.

Alzheimer’s has been a notoriously hard puzzle to solve. Despite decades of research, there are still no effective therapies and disparate theories about potential causes.

Dr. Schrag said he wouldn’t “attribute all the ills in this field” to misconduct, but it “is absolutely a part of the equation.” Some of the papers flagged for integrity issues “have been hugely influential,” he said in an interview. “Some of the labs that we’re talking about have really shaped how we’ve thought about this disease,” he said. “It’s hard to un-ring the bell.”

The fallout from fraud has a wide impact. Taxpayer dollars are wasted in the creation of the fraud and in attempts to replicate the failed experiment. Grad students — the workhorses of labs — waste time trying to repeat studies or may be bullied or intimidated into misconduct, said Elisabeth Bik, PhD, a former Stanford microbiologist who is now a full-time fraud investigator.

And there’s potential harm to patients. “There’s a lot of false hope being given to these people and their families,” Dr. Bik said in an interview.
 

Alzheimer’s Tempts With Big Rewards

There are big rewards for those who publish important papers on Alzheimer’s: More grants, publication in higher-impact journals, larger labs, and potentially, personal enrichment from commercialization of therapies.

“I can see that people are driven to cut corners or even to make up results, or even anything in between, to reach that goal,” said Dr. Bik.

It’s unclear whether misconduct and fraud are on the rise or just being detected more frequently.

“It’s very hard to say,” said Mike Rossner, PhD, president of Image Data Integrity. Institutions hire Dr. Rossner to help ferret out research integrity issues. He told this news organization that it’s likely detection is on the rise, given the increasing number of sleuths like Dr. Bik.

In 2002, Dr. Rossner began to screen all images submitted to the Journal of Clinical Biology in response to the new phenomenon of digital images and the advent of PhotoShop. “Very early on, we started to see problems in digital images that we would not have seen on a glossy printout,” Dr. Rossner said of his time as managing editor of the journal.

From 2002 to 2014, at least 25% of papers had an image that violated guidelines that prohibited the removal of spots or other blemishes (called “beautification”) with PhotoShop, which did not necessarily indicate fraud. They withdrew acceptance for 1% of papers because of image manipulations that affected data interpretation.

Dr. Bik noted that even if there is not a greater percentage of fraudulent papers in Alzheimer’s, “it would still be in absolute numbers a lot of papers that could be fraudulent,” given that Alzheimer’s research is well-funded with federal agencies alone providing $3.7 billion a year.

Images Key to Spotting Issues

Investigative sleuths often use the online forum PubPeer to initially raise questions about papers. The format gives the original authors a chance to comment on or defend their work. While some critiques are about data, most hone in on alleged duplications or manipulations of images, primarily by Western Blots.

The images are key, because “the images are the data,” said Dr. Rossner. “The words are the author’s interpretation of what they see in the images,” he said.

It’s also easier to spot a problem in an image. The raw data or an investigator’s notebooks aren’t needed, and there are artificial intelligence-driven software programs such as Proofig and Image Twin that help investigators spot duplicated images or cases in which an image might have been flipped or otherwise manipulated to make results look better.

Science recently announced that it would be using Proofig to screen images in all papers submitted to its six journals.

Using a screening tool is better than nothing, said Dr. Rossner who still relies on visual inspection, employing contrast or other features in PhotoShop to spot inconsistencies or duplications. But “none of those companies have disclosed how effective they are relative to visual screening, and that to me is very problematic,” he said.

“The tools are not going to catch everything,” said Dr. Bik.

Dr. Schrag agreed. “One of the things that we’re worried about is that a lot of the journals will simply adopt these tools as a screener and assume that that’s going to de-risk their publication portfolio,” he said, noting the high rate of misses.

Artificial Intelligence a Growing Concern

Artificial intelligence (AI) may also accelerate the amount of fraud and add to the difficulty of ferreting it out, said the investigators.

“I’m very worried about AI,” said Dr. Bik. Although AI-generated images and content may be rudimentary today, “next year it’s going to be much better,” she said. Going forward, it may be hard to distinguish between a real dataset and one that has been generated by AI, she said.

“The more closely AI can mimic authentic content, the more difficult it will be for publications to detect intentionally fraudulent submissions,” wrote Dror Kolodkin-Gal, PhD, the founder of Proofig, in an article for the Council of Science Editors.

Dr. Kolodkin-Gal said that AI may be especially prone to misuse by paper mills. Those operations submit fake or shoddy manuscripts to a journal on behalf of researchers seeking publication who pay the mills a fee. The Committee on Publication Ethics reported in 2022 that 2%-46% of papers submitted to journals may be from paper mills.

While it’s unclear whether AI is having any impact now, Dr. Rossner said, “I think I can be pretty confident in saying it is going to be a growing problem” as the tools become more sophisticated.

He sees parallels with the rise of PhotoShop and cites data from the National Institute of Health’s Office of Research Integrity (ORI) showing that in 1990, when PhotoShop was still new, 2% of cases referred to ORI involved image manipulation. By 2007, 70% of cases had image manipulation issues.

Journals, Institutions Need to Step Up More

Fraud may continue apace in part because investigations drag on for years, and in many cases, with a lack of consequences for the perpetrators, said the investigators. And, they say, journals and institutions haven’t devoted enough resources to prevent or investigate misconduct.

“A lot of editors did not even want to investigate because they just didn’t want to believe that there could be fraud in science,” said Dr. Bik of her experiences. “I hope that by now most journals at least should have realized that some proportion of the manuscripts that get sent to their journals is going to be fraud,” she said.

“The bulk of the journals seem like they don’t want to be bothered by this,” agreed Dr. Schrag, adding that “some have gone to great lengths to try to discourage people from bringing forward complaints.”

A big issue is that journals “don’t answer to any higher authority,” said Dr. Schrag. He believes that journals that repeatedly refuse to address integrity issues should be barred from publishing research produced with funds from the National Institutes of Health.

All the investigators said institutions and journals should hire forensic investigators. Relying on unpaid peer reviewers or editors to root out fraud is unrealistic, they said.

“You want to have specialized people with experience and be paid to do that as a full-time job,” said Dr. Bik, who is funded by speaking engagements and receives about $2300 a month through donations to her Patreon account.

Once a potential integrity issue is flagged, there is “an incredible conflict of interest in how these investigations are run,” said Dr. Schrag. “Institutions are asked to investigate their own faculty; they’re asked to investigate themselves.” That “creates the disincentive to move expeditiously,” said Dr. Schrag.

With the space of time, people who have committed fraud can throw out notebooks, delete data from servers, or even PhotoShop original photos so they match the manipulated ones that were submitted, Dr. Bik said.

Institutions could show they are serious about fraud by offering a “central, systematic universal screening of all image data going out of their institutions before submission to a journal,” said Dr. Rossner. But he knows only of a handful that do so. “I think research integrity offices have historically been very reactive, and they need to pivot and become proactive,” said Dr. Rossner.

Dr. Schrag wants to see stronger values within the research enterprise. “You have to build a culture where it’s absolutely anathema at a core level to violate these standards of research integrity,” he said. “We have this notion that we can push the process along faster and get to a grant and get to a paper and get to some short-term goal,” he said. “But the long-term goal in most of these cases is to cure a disease or to understand some biological mysteries. There’s no shortcut to getting there,” said Dr. Schrag.

There have been some high-profile consequences for research integrity failures, such as the 2023 resignation of Stanford University President Marc Tessier-Lavigne in the wake of findings that members of his lab — but not Tessier-Lavigne — engaged in data manipulation.

The process is often opaque, with investigations done in secrecy. “Consequences are not usually revealed, either,” said Dr. Rossner.

Dr. Schrag acknowledges it’s a tough balancing act for institutions to root out bad actors while also ensuring there’s no harm to those who may simply have operated in error.

“But it doesn’t serve anyone’s interest including the people who are accused, in dragging these things out for 5, 6, 8, or 10 years,” he said.

Lesne and Cassava: The Long and Winding Road

The investigations into the Lesne papers and the work underpinning Cassava Sciences’ therapy point to the difficulty of policing integrity and the potential fallout.

Lesne’s signature paper published in Nature in 2006 has been cited some 2300 times and is the fourth most-accessed article of 81,612 articles of a similar age in all journals tracked by Altimetrics.

Dr. Schrag, Dr. Bik, and others wrote to multiple journals asking them to investigate some 25 papers related to simufilam, including a 2012 Journal of Clinical Investigation article by Hoau-Yan Wang, PhD, the CUNY scientist whose work on simufilam has been questioned.

JCI Editor Elizabeth McNally pushed back stating in an editorial in 2022 that they, as whistleblowers, had potential conflicts and that they could be assisting short sellers who were seeking to profit by depressing Cassava’s stock price. Indeed, Dr. Schrag was initially hired by a law firm that was representing short sellers. Ms. McNally said that JCI would start requiring disclosures by whistleblowers.

Dr. Bik urged CUNY to investigate Dr. Wang in 2021 but was rebuffed. Then, in November 2023, a copy of CUNY’s final report on the Wang inquiry was leaked to Science. The university reported that Dr. Wang did not provide any original data or notebooks and that it found “long-standing and egregious misconduct in data management and record keeping by Dr. Wang,” wrote Dr. Bik in a blog post summarizing the investigation.

As of late 2023, 42 papers by Dr. Wang have earned PubPeer posts, seven have been retracted, and five have been marked with an Expression of Concern, wrote Dr. Bik.

Some have called for Cassava to stop its phase 3 studies of simufilam, but the company is proceeding, announcing in November 2023 that they have completed enrollment.

Misconduct Queries Underway at USC and Temple

Meanwhile, Dr. Schrag and Dr. Bik continue sleuthing. They are among a small group of whistleblowers who have filed a complaint with NIH about irregularities in the Zlokovic lab at USC. They allege that images were manipulated in dozens of papers, including some that inform the development of a stroke drug in phase 2 trials.

The inquiry goes well beyond stroke, said Dr. Schrag. Dr. Zlokovic “is one of the most influential scientists on Alzheimer’s scientists in the country,” Dr. Schrag said. The USC scientist is a leader on blood-brain barrier research.

USC is investigating “at some level,” he said. In a statement to this news organization, USC said that it “takes any allegations about research integrity very seriously.” The statement added, “Consistent with federal regulations and USC policies, this review must be kept confidential. As a result, we are unable to provide any further information.”

Mu Yang, PhD, assistant professor of neurobiology at Columbia University Medical Center in New York City, is also working on the Zlokovic investigation.

She calls herself an “accidental sleuth” who fell into the hobby after a graduate student asked her to help replicate a study by Temple University, Philadelphia, Pennsylvania, researcher Dominco Pratico, MD, of Alzheimer’s-like phenotype mice in the Morris Water Maze test. Dr. Yang, who runs the “behavior core” at Columbia — teaching and advising on how to run assays and collect and report data — could see right away that the Pratico data were “too perfect.”

She enlisted maze inventor Richard Morris to join her in a letter of concern to the journals that published Dr. Pratico’s work, all under the aegis of Springer Nature.

The publisher’s integrity team has since retracted four Pratico papers. Three were because of image abnormalities pointed out by Dr. Bik, who worked with Dr. Yang. One was because of “self-plagiarism.”

“The official retraction notes didn’t mention anything about data abnormality being a concern,” said Dr. Yang who says that questionable data is harder to prove than an image duplication or manipulation. And the papers remain available, although dozens of Practico papers have been flagged on PubPeer.

To Dr. Yang, images are the canary in the coalmine. “People don’t just fake western blots but then give real behavior data or give you fake behavior data but give you the most authentic Western Blots,” she said.

Dr. Pratico has now sued a graduate student who was a coauthor on the papers, according to the Philadelphia Inquirer.

The NIH’s ORI has requested that Temple University conduct an investigation, Dr. Yang said.

In a statement to this news organization, Temple said it “does not comment on internal investigations or personnel issues,” but that “allegations of research misconduct are reviewed and investigated centrally through Temple’s Office of the Vice President for Research in accordance with university policy and applicable federal regulations.”

A version of this article appeared on Medscape.com.

Alzheimer’s research is plagued with misconduct and fraud, undermining the progress toward understanding and treating the disease, say investigators who endeavor to expose errors and misleading practices.

The book is yet to be closed, for instance, on whether a 2006 paper by Sylvain Lesne positing amyloid as a major cause of Alzheimer’s was based on fraudulent data. Suspicions about the paper were first raised in late 2021 by Matthew Schrag, MD, PhD, an assistant professor of neurology at Vanderbilt University Medical Center, Nashville, Tennessee.

Dr. Schrag also queried the work of a City University of New York (CUNY) researcher who proposed PT-125 (now simufilam) as a potential anti-amyloid for Alzheimer’s disease. Even though CUNY recently found “egregious” and potentially deliberate misconduct by that researcher, Cassava Sciences is continuing phase 3 trials of simufilam.

Now questions are being raised about work from the lab of Berislav V. Zlokovic, PhD, a prominent neuroscientist at the University of Southern California (USC), Los Angeles, California, and also about studies conducted under the aegis of Domenico Pratico, MD, the director of the Alzheimer’s Center at Temple University in Philadelphia, Pennsylvania.

Alzheimer’s has been a notoriously hard puzzle to solve. Despite decades of research, there are still no effective therapies and disparate theories about potential causes.

Dr. Schrag said he wouldn’t “attribute all the ills in this field” to misconduct, but it “is absolutely a part of the equation.” Some of the papers flagged for integrity issues “have been hugely influential,” he said in an interview. “Some of the labs that we’re talking about have really shaped how we’ve thought about this disease,” he said. “It’s hard to un-ring the bell.”

The fallout from fraud has a wide impact. Taxpayer dollars are wasted in the creation of the fraud and in attempts to replicate the failed experiment. Grad students — the workhorses of labs — waste time trying to repeat studies or may be bullied or intimidated into misconduct, said Elisabeth Bik, PhD, a former Stanford microbiologist who is now a full-time fraud investigator.

And there’s potential harm to patients. “There’s a lot of false hope being given to these people and their families,” Dr. Bik said in an interview.
 

Alzheimer’s Tempts With Big Rewards

There are big rewards for those who publish important papers on Alzheimer’s: More grants, publication in higher-impact journals, larger labs, and potentially, personal enrichment from commercialization of therapies.

“I can see that people are driven to cut corners or even to make up results, or even anything in between, to reach that goal,” said Dr. Bik.

It’s unclear whether misconduct and fraud are on the rise or just being detected more frequently.

“It’s very hard to say,” said Mike Rossner, PhD, president of Image Data Integrity. Institutions hire Dr. Rossner to help ferret out research integrity issues. He told this news organization that it’s likely detection is on the rise, given the increasing number of sleuths like Dr. Bik.

In 2002, Dr. Rossner began to screen all images submitted to the Journal of Clinical Biology in response to the new phenomenon of digital images and the advent of PhotoShop. “Very early on, we started to see problems in digital images that we would not have seen on a glossy printout,” Dr. Rossner said of his time as managing editor of the journal.

From 2002 to 2014, at least 25% of papers had an image that violated guidelines that prohibited the removal of spots or other blemishes (called “beautification”) with PhotoShop, which did not necessarily indicate fraud. They withdrew acceptance for 1% of papers because of image manipulations that affected data interpretation.

Dr. Bik noted that even if there is not a greater percentage of fraudulent papers in Alzheimer’s, “it would still be in absolute numbers a lot of papers that could be fraudulent,” given that Alzheimer’s research is well-funded with federal agencies alone providing $3.7 billion a year.

Images Key to Spotting Issues

Investigative sleuths often use the online forum PubPeer to initially raise questions about papers. The format gives the original authors a chance to comment on or defend their work. While some critiques are about data, most hone in on alleged duplications or manipulations of images, primarily by Western Blots.

The images are key, because “the images are the data,” said Dr. Rossner. “The words are the author’s interpretation of what they see in the images,” he said.

It’s also easier to spot a problem in an image. The raw data or an investigator’s notebooks aren’t needed, and there are artificial intelligence-driven software programs such as Proofig and Image Twin that help investigators spot duplicated images or cases in which an image might have been flipped or otherwise manipulated to make results look better.

Science recently announced that it would be using Proofig to screen images in all papers submitted to its six journals.

Using a screening tool is better than nothing, said Dr. Rossner who still relies on visual inspection, employing contrast or other features in PhotoShop to spot inconsistencies or duplications. But “none of those companies have disclosed how effective they are relative to visual screening, and that to me is very problematic,” he said.

“The tools are not going to catch everything,” said Dr. Bik.

Dr. Schrag agreed. “One of the things that we’re worried about is that a lot of the journals will simply adopt these tools as a screener and assume that that’s going to de-risk their publication portfolio,” he said, noting the high rate of misses.

Artificial Intelligence a Growing Concern

Artificial intelligence (AI) may also accelerate the amount of fraud and add to the difficulty of ferreting it out, said the investigators.

“I’m very worried about AI,” said Dr. Bik. Although AI-generated images and content may be rudimentary today, “next year it’s going to be much better,” she said. Going forward, it may be hard to distinguish between a real dataset and one that has been generated by AI, she said.

“The more closely AI can mimic authentic content, the more difficult it will be for publications to detect intentionally fraudulent submissions,” wrote Dror Kolodkin-Gal, PhD, the founder of Proofig, in an article for the Council of Science Editors.

Dr. Kolodkin-Gal said that AI may be especially prone to misuse by paper mills. Those operations submit fake or shoddy manuscripts to a journal on behalf of researchers seeking publication who pay the mills a fee. The Committee on Publication Ethics reported in 2022 that 2%-46% of papers submitted to journals may be from paper mills.

While it’s unclear whether AI is having any impact now, Dr. Rossner said, “I think I can be pretty confident in saying it is going to be a growing problem” as the tools become more sophisticated.

He sees parallels with the rise of PhotoShop and cites data from the National Institute of Health’s Office of Research Integrity (ORI) showing that in 1990, when PhotoShop was still new, 2% of cases referred to ORI involved image manipulation. By 2007, 70% of cases had image manipulation issues.

Journals, Institutions Need to Step Up More

Fraud may continue apace in part because investigations drag on for years, and in many cases, with a lack of consequences for the perpetrators, said the investigators. And, they say, journals and institutions haven’t devoted enough resources to prevent or investigate misconduct.

“A lot of editors did not even want to investigate because they just didn’t want to believe that there could be fraud in science,” said Dr. Bik of her experiences. “I hope that by now most journals at least should have realized that some proportion of the manuscripts that get sent to their journals is going to be fraud,” she said.

“The bulk of the journals seem like they don’t want to be bothered by this,” agreed Dr. Schrag, adding that “some have gone to great lengths to try to discourage people from bringing forward complaints.”

A big issue is that journals “don’t answer to any higher authority,” said Dr. Schrag. He believes that journals that repeatedly refuse to address integrity issues should be barred from publishing research produced with funds from the National Institutes of Health.

All the investigators said institutions and journals should hire forensic investigators. Relying on unpaid peer reviewers or editors to root out fraud is unrealistic, they said.

“You want to have specialized people with experience and be paid to do that as a full-time job,” said Dr. Bik, who is funded by speaking engagements and receives about $2300 a month through donations to her Patreon account.

Once a potential integrity issue is flagged, there is “an incredible conflict of interest in how these investigations are run,” said Dr. Schrag. “Institutions are asked to investigate their own faculty; they’re asked to investigate themselves.” That “creates the disincentive to move expeditiously,” said Dr. Schrag.

With the space of time, people who have committed fraud can throw out notebooks, delete data from servers, or even PhotoShop original photos so they match the manipulated ones that were submitted, Dr. Bik said.

Institutions could show they are serious about fraud by offering a “central, systematic universal screening of all image data going out of their institutions before submission to a journal,” said Dr. Rossner. But he knows only of a handful that do so. “I think research integrity offices have historically been very reactive, and they need to pivot and become proactive,” said Dr. Rossner.

Dr. Schrag wants to see stronger values within the research enterprise. “You have to build a culture where it’s absolutely anathema at a core level to violate these standards of research integrity,” he said. “We have this notion that we can push the process along faster and get to a grant and get to a paper and get to some short-term goal,” he said. “But the long-term goal in most of these cases is to cure a disease or to understand some biological mysteries. There’s no shortcut to getting there,” said Dr. Schrag.

There have been some high-profile consequences for research integrity failures, such as the 2023 resignation of Stanford University President Marc Tessier-Lavigne in the wake of findings that members of his lab — but not Tessier-Lavigne — engaged in data manipulation.

The process is often opaque, with investigations done in secrecy. “Consequences are not usually revealed, either,” said Dr. Rossner.

Dr. Schrag acknowledges it’s a tough balancing act for institutions to root out bad actors while also ensuring there’s no harm to those who may simply have operated in error.

“But it doesn’t serve anyone’s interest including the people who are accused, in dragging these things out for 5, 6, 8, or 10 years,” he said.

Lesne and Cassava: The Long and Winding Road

The investigations into the Lesne papers and the work underpinning Cassava Sciences’ therapy point to the difficulty of policing integrity and the potential fallout.

Lesne’s signature paper published in Nature in 2006 has been cited some 2300 times and is the fourth most-accessed article of 81,612 articles of a similar age in all journals tracked by Altimetrics.

Dr. Schrag, Dr. Bik, and others wrote to multiple journals asking them to investigate some 25 papers related to simufilam, including a 2012 Journal of Clinical Investigation article by Hoau-Yan Wang, PhD, the CUNY scientist whose work on simufilam has been questioned.

JCI Editor Elizabeth McNally pushed back stating in an editorial in 2022 that they, as whistleblowers, had potential conflicts and that they could be assisting short sellers who were seeking to profit by depressing Cassava’s stock price. Indeed, Dr. Schrag was initially hired by a law firm that was representing short sellers. Ms. McNally said that JCI would start requiring disclosures by whistleblowers.

Dr. Bik urged CUNY to investigate Dr. Wang in 2021 but was rebuffed. Then, in November 2023, a copy of CUNY’s final report on the Wang inquiry was leaked to Science. The university reported that Dr. Wang did not provide any original data or notebooks and that it found “long-standing and egregious misconduct in data management and record keeping by Dr. Wang,” wrote Dr. Bik in a blog post summarizing the investigation.

As of late 2023, 42 papers by Dr. Wang have earned PubPeer posts, seven have been retracted, and five have been marked with an Expression of Concern, wrote Dr. Bik.

Some have called for Cassava to stop its phase 3 studies of simufilam, but the company is proceeding, announcing in November 2023 that they have completed enrollment.

Misconduct Queries Underway at USC and Temple

Meanwhile, Dr. Schrag and Dr. Bik continue sleuthing. They are among a small group of whistleblowers who have filed a complaint with NIH about irregularities in the Zlokovic lab at USC. They allege that images were manipulated in dozens of papers, including some that inform the development of a stroke drug in phase 2 trials.

The inquiry goes well beyond stroke, said Dr. Schrag. Dr. Zlokovic “is one of the most influential scientists on Alzheimer’s scientists in the country,” Dr. Schrag said. The USC scientist is a leader on blood-brain barrier research.

USC is investigating “at some level,” he said. In a statement to this news organization, USC said that it “takes any allegations about research integrity very seriously.” The statement added, “Consistent with federal regulations and USC policies, this review must be kept confidential. As a result, we are unable to provide any further information.”

Mu Yang, PhD, assistant professor of neurobiology at Columbia University Medical Center in New York City, is also working on the Zlokovic investigation.

She calls herself an “accidental sleuth” who fell into the hobby after a graduate student asked her to help replicate a study by Temple University, Philadelphia, Pennsylvania, researcher Dominco Pratico, MD, of Alzheimer’s-like phenotype mice in the Morris Water Maze test. Dr. Yang, who runs the “behavior core” at Columbia — teaching and advising on how to run assays and collect and report data — could see right away that the Pratico data were “too perfect.”

She enlisted maze inventor Richard Morris to join her in a letter of concern to the journals that published Dr. Pratico’s work, all under the aegis of Springer Nature.

The publisher’s integrity team has since retracted four Pratico papers. Three were because of image abnormalities pointed out by Dr. Bik, who worked with Dr. Yang. One was because of “self-plagiarism.”

“The official retraction notes didn’t mention anything about data abnormality being a concern,” said Dr. Yang who says that questionable data is harder to prove than an image duplication or manipulation. And the papers remain available, although dozens of Practico papers have been flagged on PubPeer.

To Dr. Yang, images are the canary in the coalmine. “People don’t just fake western blots but then give real behavior data or give you fake behavior data but give you the most authentic Western Blots,” she said.

Dr. Pratico has now sued a graduate student who was a coauthor on the papers, according to the Philadelphia Inquirer.

The NIH’s ORI has requested that Temple University conduct an investigation, Dr. Yang said.

In a statement to this news organization, Temple said it “does not comment on internal investigations or personnel issues,” but that “allegations of research misconduct are reviewed and investigated centrally through Temple’s Office of the Vice President for Research in accordance with university policy and applicable federal regulations.”

A version of this article appeared on Medscape.com.

Alzheimer’s research is plagued with misconduct and fraud, undermining the progress toward understanding and treating the disease, say investigators who endeavor to expose errors and misleading practices.

The book is yet to be closed, for instance, on whether a 2006 paper by Sylvain Lesne positing amyloid as a major cause of Alzheimer’s was based on fraudulent data. Suspicions about the paper were first raised in late 2021 by Matthew Schrag, MD, PhD, an assistant professor of neurology at Vanderbilt University Medical Center, Nashville, Tennessee.

Dr. Schrag also queried the work of a City University of New York (CUNY) researcher who proposed PT-125 (now simufilam) as a potential anti-amyloid for Alzheimer’s disease. Even though CUNY recently found “egregious” and potentially deliberate misconduct by that researcher, Cassava Sciences is continuing phase 3 trials of simufilam.

Now questions are being raised about work from the lab of Berislav V. Zlokovic, PhD, a prominent neuroscientist at the University of Southern California (USC), Los Angeles, California, and also about studies conducted under the aegis of Domenico Pratico, MD, the director of the Alzheimer’s Center at Temple University in Philadelphia, Pennsylvania.

Alzheimer’s has been a notoriously hard puzzle to solve. Despite decades of research, there are still no effective therapies and disparate theories about potential causes.

Dr. Schrag said he wouldn’t “attribute all the ills in this field” to misconduct, but it “is absolutely a part of the equation.” Some of the papers flagged for integrity issues “have been hugely influential,” he said in an interview. “Some of the labs that we’re talking about have really shaped how we’ve thought about this disease,” he said. “It’s hard to un-ring the bell.”

The fallout from fraud has a wide impact. Taxpayer dollars are wasted in the creation of the fraud and in attempts to replicate the failed experiment. Grad students — the workhorses of labs — waste time trying to repeat studies or may be bullied or intimidated into misconduct, said Elisabeth Bik, PhD, a former Stanford microbiologist who is now a full-time fraud investigator.

And there’s potential harm to patients. “There’s a lot of false hope being given to these people and their families,” Dr. Bik said in an interview.
 

Alzheimer’s Tempts With Big Rewards

There are big rewards for those who publish important papers on Alzheimer’s: More grants, publication in higher-impact journals, larger labs, and potentially, personal enrichment from commercialization of therapies.

“I can see that people are driven to cut corners or even to make up results, or even anything in between, to reach that goal,” said Dr. Bik.

It’s unclear whether misconduct and fraud are on the rise or just being detected more frequently.

“It’s very hard to say,” said Mike Rossner, PhD, president of Image Data Integrity. Institutions hire Dr. Rossner to help ferret out research integrity issues. He told this news organization that it’s likely detection is on the rise, given the increasing number of sleuths like Dr. Bik.

In 2002, Dr. Rossner began to screen all images submitted to the Journal of Clinical Biology in response to the new phenomenon of digital images and the advent of PhotoShop. “Very early on, we started to see problems in digital images that we would not have seen on a glossy printout,” Dr. Rossner said of his time as managing editor of the journal.

From 2002 to 2014, at least 25% of papers had an image that violated guidelines that prohibited the removal of spots or other blemishes (called “beautification”) with PhotoShop, which did not necessarily indicate fraud. They withdrew acceptance for 1% of papers because of image manipulations that affected data interpretation.

Dr. Bik noted that even if there is not a greater percentage of fraudulent papers in Alzheimer’s, “it would still be in absolute numbers a lot of papers that could be fraudulent,” given that Alzheimer’s research is well-funded with federal agencies alone providing $3.7 billion a year.

Images Key to Spotting Issues

Investigative sleuths often use the online forum PubPeer to initially raise questions about papers. The format gives the original authors a chance to comment on or defend their work. While some critiques are about data, most hone in on alleged duplications or manipulations of images, primarily by Western Blots.

The images are key, because “the images are the data,” said Dr. Rossner. “The words are the author’s interpretation of what they see in the images,” he said.

It’s also easier to spot a problem in an image. The raw data or an investigator’s notebooks aren’t needed, and there are artificial intelligence-driven software programs such as Proofig and Image Twin that help investigators spot duplicated images or cases in which an image might have been flipped or otherwise manipulated to make results look better.

Science recently announced that it would be using Proofig to screen images in all papers submitted to its six journals.

Using a screening tool is better than nothing, said Dr. Rossner who still relies on visual inspection, employing contrast or other features in PhotoShop to spot inconsistencies or duplications. But “none of those companies have disclosed how effective they are relative to visual screening, and that to me is very problematic,” he said.

“The tools are not going to catch everything,” said Dr. Bik.

Dr. Schrag agreed. “One of the things that we’re worried about is that a lot of the journals will simply adopt these tools as a screener and assume that that’s going to de-risk their publication portfolio,” he said, noting the high rate of misses.

Artificial Intelligence a Growing Concern

Artificial intelligence (AI) may also accelerate the amount of fraud and add to the difficulty of ferreting it out, said the investigators.

“I’m very worried about AI,” said Dr. Bik. Although AI-generated images and content may be rudimentary today, “next year it’s going to be much better,” she said. Going forward, it may be hard to distinguish between a real dataset and one that has been generated by AI, she said.

“The more closely AI can mimic authentic content, the more difficult it will be for publications to detect intentionally fraudulent submissions,” wrote Dror Kolodkin-Gal, PhD, the founder of Proofig, in an article for the Council of Science Editors.

Dr. Kolodkin-Gal said that AI may be especially prone to misuse by paper mills. Those operations submit fake or shoddy manuscripts to a journal on behalf of researchers seeking publication who pay the mills a fee. The Committee on Publication Ethics reported in 2022 that 2%-46% of papers submitted to journals may be from paper mills.

While it’s unclear whether AI is having any impact now, Dr. Rossner said, “I think I can be pretty confident in saying it is going to be a growing problem” as the tools become more sophisticated.

He sees parallels with the rise of PhotoShop and cites data from the National Institute of Health’s Office of Research Integrity (ORI) showing that in 1990, when PhotoShop was still new, 2% of cases referred to ORI involved image manipulation. By 2007, 70% of cases had image manipulation issues.

Journals, Institutions Need to Step Up More

Fraud may continue apace in part because investigations drag on for years, and in many cases, with a lack of consequences for the perpetrators, said the investigators. And, they say, journals and institutions haven’t devoted enough resources to prevent or investigate misconduct.

“A lot of editors did not even want to investigate because they just didn’t want to believe that there could be fraud in science,” said Dr. Bik of her experiences. “I hope that by now most journals at least should have realized that some proportion of the manuscripts that get sent to their journals is going to be fraud,” she said.

“The bulk of the journals seem like they don’t want to be bothered by this,” agreed Dr. Schrag, adding that “some have gone to great lengths to try to discourage people from bringing forward complaints.”

A big issue is that journals “don’t answer to any higher authority,” said Dr. Schrag. He believes that journals that repeatedly refuse to address integrity issues should be barred from publishing research produced with funds from the National Institutes of Health.

All the investigators said institutions and journals should hire forensic investigators. Relying on unpaid peer reviewers or editors to root out fraud is unrealistic, they said.

“You want to have specialized people with experience and be paid to do that as a full-time job,” said Dr. Bik, who is funded by speaking engagements and receives about $2300 a month through donations to her Patreon account.

Once a potential integrity issue is flagged, there is “an incredible conflict of interest in how these investigations are run,” said Dr. Schrag. “Institutions are asked to investigate their own faculty; they’re asked to investigate themselves.” That “creates the disincentive to move expeditiously,” said Dr. Schrag.

With the space of time, people who have committed fraud can throw out notebooks, delete data from servers, or even PhotoShop original photos so they match the manipulated ones that were submitted, Dr. Bik said.

Institutions could show they are serious about fraud by offering a “central, systematic universal screening of all image data going out of their institutions before submission to a journal,” said Dr. Rossner. But he knows only of a handful that do so. “I think research integrity offices have historically been very reactive, and they need to pivot and become proactive,” said Dr. Rossner.

Dr. Schrag wants to see stronger values within the research enterprise. “You have to build a culture where it’s absolutely anathema at a core level to violate these standards of research integrity,” he said. “We have this notion that we can push the process along faster and get to a grant and get to a paper and get to some short-term goal,” he said. “But the long-term goal in most of these cases is to cure a disease or to understand some biological mysteries. There’s no shortcut to getting there,” said Dr. Schrag.

There have been some high-profile consequences for research integrity failures, such as the 2023 resignation of Stanford University President Marc Tessier-Lavigne in the wake of findings that members of his lab — but not Tessier-Lavigne — engaged in data manipulation.

The process is often opaque, with investigations done in secrecy. “Consequences are not usually revealed, either,” said Dr. Rossner.

Dr. Schrag acknowledges it’s a tough balancing act for institutions to root out bad actors while also ensuring there’s no harm to those who may simply have operated in error.

“But it doesn’t serve anyone’s interest including the people who are accused, in dragging these things out for 5, 6, 8, or 10 years,” he said.

Lesne and Cassava: The Long and Winding Road

The investigations into the Lesne papers and the work underpinning Cassava Sciences’ therapy point to the difficulty of policing integrity and the potential fallout.

Lesne’s signature paper published in Nature in 2006 has been cited some 2300 times and is the fourth most-accessed article of 81,612 articles of a similar age in all journals tracked by Altimetrics.

Dr. Schrag, Dr. Bik, and others wrote to multiple journals asking them to investigate some 25 papers related to simufilam, including a 2012 Journal of Clinical Investigation article by Hoau-Yan Wang, PhD, the CUNY scientist whose work on simufilam has been questioned.

JCI Editor Elizabeth McNally pushed back stating in an editorial in 2022 that they, as whistleblowers, had potential conflicts and that they could be assisting short sellers who were seeking to profit by depressing Cassava’s stock price. Indeed, Dr. Schrag was initially hired by a law firm that was representing short sellers. Ms. McNally said that JCI would start requiring disclosures by whistleblowers.

Dr. Bik urged CUNY to investigate Dr. Wang in 2021 but was rebuffed. Then, in November 2023, a copy of CUNY’s final report on the Wang inquiry was leaked to Science. The university reported that Dr. Wang did not provide any original data or notebooks and that it found “long-standing and egregious misconduct in data management and record keeping by Dr. Wang,” wrote Dr. Bik in a blog post summarizing the investigation.

As of late 2023, 42 papers by Dr. Wang have earned PubPeer posts, seven have been retracted, and five have been marked with an Expression of Concern, wrote Dr. Bik.

Some have called for Cassava to stop its phase 3 studies of simufilam, but the company is proceeding, announcing in November 2023 that they have completed enrollment.

Misconduct Queries Underway at USC and Temple

Meanwhile, Dr. Schrag and Dr. Bik continue sleuthing. They are among a small group of whistleblowers who have filed a complaint with NIH about irregularities in the Zlokovic lab at USC. They allege that images were manipulated in dozens of papers, including some that inform the development of a stroke drug in phase 2 trials.

The inquiry goes well beyond stroke, said Dr. Schrag. Dr. Zlokovic “is one of the most influential scientists on Alzheimer’s scientists in the country,” Dr. Schrag said. The USC scientist is a leader on blood-brain barrier research.

USC is investigating “at some level,” he said. In a statement to this news organization, USC said that it “takes any allegations about research integrity very seriously.” The statement added, “Consistent with federal regulations and USC policies, this review must be kept confidential. As a result, we are unable to provide any further information.”

Mu Yang, PhD, assistant professor of neurobiology at Columbia University Medical Center in New York City, is also working on the Zlokovic investigation.

She calls herself an “accidental sleuth” who fell into the hobby after a graduate student asked her to help replicate a study by Temple University, Philadelphia, Pennsylvania, researcher Dominco Pratico, MD, of Alzheimer’s-like phenotype mice in the Morris Water Maze test. Dr. Yang, who runs the “behavior core” at Columbia — teaching and advising on how to run assays and collect and report data — could see right away that the Pratico data were “too perfect.”

She enlisted maze inventor Richard Morris to join her in a letter of concern to the journals that published Dr. Pratico’s work, all under the aegis of Springer Nature.

The publisher’s integrity team has since retracted four Pratico papers. Three were because of image abnormalities pointed out by Dr. Bik, who worked with Dr. Yang. One was because of “self-plagiarism.”

“The official retraction notes didn’t mention anything about data abnormality being a concern,” said Dr. Yang who says that questionable data is harder to prove than an image duplication or manipulation. And the papers remain available, although dozens of Practico papers have been flagged on PubPeer.

To Dr. Yang, images are the canary in the coalmine. “People don’t just fake western blots but then give real behavior data or give you fake behavior data but give you the most authentic Western Blots,” she said.

Dr. Pratico has now sued a graduate student who was a coauthor on the papers, according to the Philadelphia Inquirer.

The NIH’s ORI has requested that Temple University conduct an investigation, Dr. Yang said.

In a statement to this news organization, Temple said it “does not comment on internal investigations or personnel issues,” but that “allegations of research misconduct are reviewed and investigated centrally through Temple’s Office of the Vice President for Research in accordance with university policy and applicable federal regulations.”

A version of this article appeared on Medscape.com.

Working with medically trained service dogs is associated with a 31% reduction in seizures compared with usual care in treatment-resistant epilepsy, a new study showed.

Investigators speculate that the dogs may ease participants’ stress, leading to a decrease in seizure frequency, although they note this relationship warrants more study.

“Despite the development of numerous antiseizure medications over the past 15 years, up to 30% of people with epilepsy experience persistent seizures,” study author Valérie van Hezik-Wester, MSc, of Erasmus University Rotterdam, Rotterdam, the Netherlands, said in a press release.

The unpredictable nature of seizures is one of the most disabling aspects of epilepsy, Ms. Hezik-Wester added. Seizure dogs are trained to recognize seizures and respond when they occur.

“The tasks that these dogs perform, along with their companionship, may reduce seizure-related anxiety, also potentially reducing seizures caused by stress, the most common trigger for seizures,” she said.

The findings were published online in Neurology.
 

Improve Quality of Life

The study included 25 individuals with medically refractory epilepsy who had an average of two or more seizures per week, with seizure characteristics associated with a high risk for injuries or dysfunction. They also had to be able to care for a service dog.

All were observed under usual care, which included antiseizure medications, neurostimulation devices, and other supportive therapies. Participants could then choose to work with a service dog that had completed socialization and obedience training or be assigned a puppy they would train at home.

The median follow-up was 19 months with usual care and 12 months with the intervention. Participants recorded seizure activity in diaries and completed surveys on seizure severity, quality of life, and well-being every 3 months. Daily seizure counts were converted to obtain cumulative seizure frequencies over 28-day periods.

Of the 25 original participants, six discontinued trial participation before the end of follow-up, four of whom left the study due to difficulty with dog care and training.

Participants receiving usual care reported an average of 115 seizures per 28-day period, while those with trained service dogs recorded 73 seizures in the same period, or a 37% difference between groups.

Researchers found that participants had an average of 31% fewer seizures during the past 3 months when they had seizure dogs, with seven participants achieving a 50%-100% reduction in seizures.

The number of seizure-free days increased from an average of 11 days per 28-day period before receiving a service dog to 15 days after working with a dog.

Scores on the EQ-5D-5L, which measures perceived health problems, decreased on average by 2.5% per consecutive 28-day period with the intervention, reflecting an increase in generic health-related quality of life (0.975; 95% CI, 0.954-0.997).

“These findings show that seizure dogs can help people with epilepsy,” said Ms. van Hezik-Wester. “However, we also found that this partnership with seizure dogs might not be the right fit for everyone, as some people discontinued their participation in this program. More research is needed to better understand which people can benefit from working with seizure dogs.”
 

Enhanced Quality of Life

In an accompanying editorial, Amir Mbonde, MB, and Amy Crepeau, MD, of Mayo Clinic in Phoenix, Arizona, noted the findings add to a growing body of work on the effectiveness of service dogs in reducing seizure frequency.

“In addition to improved seizure control, the EPISODE study demonstrated the benefit of seizure dogs in enhancing the quality of life for patients, a crucial component of comprehensive epilepsy care,” they wrote.

In prior studies, seizure dogs have identified an odor that a person emits before a seizure in up to 97% of people, they noted, adding that this ability “offers immense clinical benefits to people with epilepsy, enhancing their independence, social engagement, employment opportunities, self-confidence, and thus quality of life.”

Study limitations include its small sample size and high attrition rate.

The study was funded by the Netherlands Organization for Health Research and Development and Innovatiefonds Zorgverzekeraars.

A version of this article appeared on Medscape.com.

Working with medically trained service dogs is associated with a 31% reduction in seizures compared with usual care in treatment-resistant epilepsy, a new study showed.

Investigators speculate that the dogs may ease participants’ stress, leading to a decrease in seizure frequency, although they note this relationship warrants more study.

“Despite the development of numerous antiseizure medications over the past 15 years, up to 30% of people with epilepsy experience persistent seizures,” study author Valérie van Hezik-Wester, MSc, of Erasmus University Rotterdam, Rotterdam, the Netherlands, said in a press release.

The unpredictable nature of seizures is one of the most disabling aspects of epilepsy, Ms. Hezik-Wester added. Seizure dogs are trained to recognize seizures and respond when they occur.

“The tasks that these dogs perform, along with their companionship, may reduce seizure-related anxiety, also potentially reducing seizures caused by stress, the most common trigger for seizures,” she said.

The findings were published online in Neurology.
 

Improve Quality of Life

The study included 25 individuals with medically refractory epilepsy who had an average of two or more seizures per week, with seizure characteristics associated with a high risk for injuries or dysfunction. They also had to be able to care for a service dog.

All were observed under usual care, which included antiseizure medications, neurostimulation devices, and other supportive therapies. Participants could then choose to work with a service dog that had completed socialization and obedience training or be assigned a puppy they would train at home.

The median follow-up was 19 months with usual care and 12 months with the intervention. Participants recorded seizure activity in diaries and completed surveys on seizure severity, quality of life, and well-being every 3 months. Daily seizure counts were converted to obtain cumulative seizure frequencies over 28-day periods.

Of the 25 original participants, six discontinued trial participation before the end of follow-up, four of whom left the study due to difficulty with dog care and training.

Participants receiving usual care reported an average of 115 seizures per 28-day period, while those with trained service dogs recorded 73 seizures in the same period, or a 37% difference between groups.

Researchers found that participants had an average of 31% fewer seizures during the past 3 months when they had seizure dogs, with seven participants achieving a 50%-100% reduction in seizures.

The number of seizure-free days increased from an average of 11 days per 28-day period before receiving a service dog to 15 days after working with a dog.

Scores on the EQ-5D-5L, which measures perceived health problems, decreased on average by 2.5% per consecutive 28-day period with the intervention, reflecting an increase in generic health-related quality of life (0.975; 95% CI, 0.954-0.997).

“These findings show that seizure dogs can help people with epilepsy,” said Ms. van Hezik-Wester. “However, we also found that this partnership with seizure dogs might not be the right fit for everyone, as some people discontinued their participation in this program. More research is needed to better understand which people can benefit from working with seizure dogs.”
 

Enhanced Quality of Life

In an accompanying editorial, Amir Mbonde, MB, and Amy Crepeau, MD, of Mayo Clinic in Phoenix, Arizona, noted the findings add to a growing body of work on the effectiveness of service dogs in reducing seizure frequency.

“In addition to improved seizure control, the EPISODE study demonstrated the benefit of seizure dogs in enhancing the quality of life for patients, a crucial component of comprehensive epilepsy care,” they wrote.

In prior studies, seizure dogs have identified an odor that a person emits before a seizure in up to 97% of people, they noted, adding that this ability “offers immense clinical benefits to people with epilepsy, enhancing their independence, social engagement, employment opportunities, self-confidence, and thus quality of life.”

Study limitations include its small sample size and high attrition rate.

The study was funded by the Netherlands Organization for Health Research and Development and Innovatiefonds Zorgverzekeraars.

A version of this article appeared on Medscape.com.

Working with medically trained service dogs is associated with a 31% reduction in seizures compared with usual care in treatment-resistant epilepsy, a new study showed.

Investigators speculate that the dogs may ease participants’ stress, leading to a decrease in seizure frequency, although they note this relationship warrants more study.

“Despite the development of numerous antiseizure medications over the past 15 years, up to 30% of people with epilepsy experience persistent seizures,” study author Valérie van Hezik-Wester, MSc, of Erasmus University Rotterdam, Rotterdam, the Netherlands, said in a press release.

The unpredictable nature of seizures is one of the most disabling aspects of epilepsy, Ms. Hezik-Wester added. Seizure dogs are trained to recognize seizures and respond when they occur.

“The tasks that these dogs perform, along with their companionship, may reduce seizure-related anxiety, also potentially reducing seizures caused by stress, the most common trigger for seizures,” she said.

The findings were published online in Neurology.
 

Improve Quality of Life

The study included 25 individuals with medically refractory epilepsy who had an average of two or more seizures per week, with seizure characteristics associated with a high risk for injuries or dysfunction. They also had to be able to care for a service dog.

All were observed under usual care, which included antiseizure medications, neurostimulation devices, and other supportive therapies. Participants could then choose to work with a service dog that had completed socialization and obedience training or be assigned a puppy they would train at home.

The median follow-up was 19 months with usual care and 12 months with the intervention. Participants recorded seizure activity in diaries and completed surveys on seizure severity, quality of life, and well-being every 3 months. Daily seizure counts were converted to obtain cumulative seizure frequencies over 28-day periods.

Of the 25 original participants, six discontinued trial participation before the end of follow-up, four of whom left the study due to difficulty with dog care and training.

Participants receiving usual care reported an average of 115 seizures per 28-day period, while those with trained service dogs recorded 73 seizures in the same period, or a 37% difference between groups.

Researchers found that participants had an average of 31% fewer seizures during the past 3 months when they had seizure dogs, with seven participants achieving a 50%-100% reduction in seizures.

The number of seizure-free days increased from an average of 11 days per 28-day period before receiving a service dog to 15 days after working with a dog.

Scores on the EQ-5D-5L, which measures perceived health problems, decreased on average by 2.5% per consecutive 28-day period with the intervention, reflecting an increase in generic health-related quality of life (0.975; 95% CI, 0.954-0.997).

“These findings show that seizure dogs can help people with epilepsy,” said Ms. van Hezik-Wester. “However, we also found that this partnership with seizure dogs might not be the right fit for everyone, as some people discontinued their participation in this program. More research is needed to better understand which people can benefit from working with seizure dogs.”
 

Enhanced Quality of Life

In an accompanying editorial, Amir Mbonde, MB, and Amy Crepeau, MD, of Mayo Clinic in Phoenix, Arizona, noted the findings add to a growing body of work on the effectiveness of service dogs in reducing seizure frequency.

“In addition to improved seizure control, the EPISODE study demonstrated the benefit of seizure dogs in enhancing the quality of life for patients, a crucial component of comprehensive epilepsy care,” they wrote.

In prior studies, seizure dogs have identified an odor that a person emits before a seizure in up to 97% of people, they noted, adding that this ability “offers immense clinical benefits to people with epilepsy, enhancing their independence, social engagement, employment opportunities, self-confidence, and thus quality of life.”

Study limitations include its small sample size and high attrition rate.

The study was funded by the Netherlands Organization for Health Research and Development and Innovatiefonds Zorgverzekeraars.

A version of this article appeared on Medscape.com.