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PTSD symptoms common in families of COVID-19 patients
The pandemic has significantly affected the mental health of family members of patients with COVID-19, including high rates of posttraumatic stress disorder (PTSD), anxiety, and depression, new research suggests.
They also had a higher prevalence of depression and anxiety symptoms.
The results illustrate how the mental health of families has been adversely affected by strict isolation measures instituted at the height of the COVID pandemic, lead author Elie Azoulay, MD, PhD, professor of medicine at Diderot University and director of the Medical Intensive Care Unit, Saint Louis Hospital, Paris, told this news organization.
Such restrictions were unnecessary, Dr. Azoulay noted, adding that everyone, including health care professionals, benefits when families are allowed to interact with their loved ones in the ICU.
He added the study findings also emphasize the importance of social supports.
“We need to develop and really increase what we can do for family members” of patients staying in the ICU, said Dr. Azoulay.
The findings were published online Feb. 18 in JAMA.
Twenty-three ICUs in France
The study included adult family members of patients admitted with ARDS to 23 ICUs in France from January to October 2020.
Patients had a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) of less than 300, and bilateral opacities on chest radiography not fully explained by cardiac failure or fluid overload.
Two trained clinical psychologists interviewed family members and patients by telephone a median of 112 days after ICU discharge. During this interview, participants completed the Impact of Event Scale Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS).
The IES-R score ranges from 0 (best) to 88 (worst) with a score of more than 22 indicating presence of PTSD-related symptoms of clinical concern. The HADS has separate subscales for anxiety and depression, with a score of 7 or greater on a 21-point scale indicating symptoms of anxiety or depression.
Family members also rated social supports on a scale from 0 (extremely limited) to 10 (extremely effective). Dr. Azoulay noted that social support is the subjective perception of the extent to which friends, mental health specialists, and others are available and helpful.
Investigators divided patients into two groups depending on whether or not the cause of ARDS was COVID-19. Causes other than COVID-19 mainly included community-acquired pneumonia and influenza.
The primary outcome was the prevalence of PTSD-related symptoms among family members. Secondary outcomes were the prevalence of anxiety and depression in family members.
The analysis included 303 family members of patients with COVID-19 ARDS and 214 family members of patients with non–COVID-19 ARDS. Almost half of the family members were spouses.
Those with family members with COVID-19 were younger than the non-COVID group (median age, 50 vs. 55 years). They were less frequently allowed to visit the ICU (35% vs. 88%) and more commonly received patient information by phone (84% vs. 20%).
Better strategies needed
Results showed PTSD symptoms were significantly more common in family members of patients with than without COVID-10 (35% vs. 19%; difference of 16%; 95% confidence interval, 8%-24%; P < .001).
Anxiety symptoms were significantly more common in the COVID-19 group (41% vs. 34%; difference of 8%; 95% CI, 0%-16%; P = .05), as were depression symptoms (31% vs. 18%; difference of 13%; 95% CI, 6%-21%; P < .001).
About 26% of the hospitalized relatives died. PTSD symptoms were more common among bereaved family members of patients who died from COVID-19 than of patients without COVID-19 (63% vs. 39%; difference of 24%; 95% CI, 7%-40%; P = .008).
In the COVID-19 group, significantly fewer family members reported having attended the funeral (77% vs. 91%, P = .04). This could be because of concerns over transmitting the virus, the investigators noted.
After adjustment for age, sex, and level of social support in a multivariable analysis, COVID-19 ARDS was significantly associated with increased risk for PTSD-related symptoms in family members (odds ratio, 2.05; 95% CI, 1.30-3.23; P =.002).
Other factors independently associated with PTSD symptoms were age, level of social support, and being male.
Factors associated with anxiety included having COVID-19 ARDS, age, being male, and level of social support. COVID-19 ARDS and level of social support were independently associated with depression.
Although isolation measures were implemented to prevent viral transmission during the pandemic, severely restricting family members from interacting with their sick loved ones in the ICU is “very destructive [and] deeply distressing,” said Dr. Azoulay. “It’s almost cruel.”
Fear may be at the heart of the “psycho-trauma” experienced by family members, he said.
“I would say one of the main sources is fear of getting infected, fear of abandoning family members, fear of leaving the kids alone without any support, and fear of infecting others,” he added.
Health care providers should develop strategies to better communicate with family members, who also feel a lot of guilt when they’re unable to be with their sick loved ones, said Dr. Azoulay.
‘Element of fear’
Commenting on the findings for this news organization, O. Joseph Bienvenu, MD, PhD, professor of psychiatry and behavioral sciences at Johns Hopkins Medicine, Baltimore, called the study “solid” and noted the lead author is “a well-recognized clinical researcher.”
It was “remarkable” that investigators were able to include a control group of family members of patients with ARDS not due to COVID-19, added Dr. Bienvenu, who was not involved with the research.
“It sounds like the bottom line is COVID adds an additional element of fear in loved ones,” he said.
Dr. Bienvenu added this fits with his own clinical experience – and noted that some COVID-19 follow-up clinics now include family members in their assessments and care.
“I think this study nicely illustrates the utility of this,” he concluded.
The study received funding from the French Ministry of Health. Dr. Azoulay reported receipt of personal fees from lectures from Pfizer, Gilead, Baxter, and Alexion, and institutional research grants from Merck Sharp and Dohme, Pfizer, Baxter, and Alexion. Dr. Bienvenu has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The pandemic has significantly affected the mental health of family members of patients with COVID-19, including high rates of posttraumatic stress disorder (PTSD), anxiety, and depression, new research suggests.
They also had a higher prevalence of depression and anxiety symptoms.
The results illustrate how the mental health of families has been adversely affected by strict isolation measures instituted at the height of the COVID pandemic, lead author Elie Azoulay, MD, PhD, professor of medicine at Diderot University and director of the Medical Intensive Care Unit, Saint Louis Hospital, Paris, told this news organization.
Such restrictions were unnecessary, Dr. Azoulay noted, adding that everyone, including health care professionals, benefits when families are allowed to interact with their loved ones in the ICU.
He added the study findings also emphasize the importance of social supports.
“We need to develop and really increase what we can do for family members” of patients staying in the ICU, said Dr. Azoulay.
The findings were published online Feb. 18 in JAMA.
Twenty-three ICUs in France
The study included adult family members of patients admitted with ARDS to 23 ICUs in France from January to October 2020.
Patients had a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) of less than 300, and bilateral opacities on chest radiography not fully explained by cardiac failure or fluid overload.
Two trained clinical psychologists interviewed family members and patients by telephone a median of 112 days after ICU discharge. During this interview, participants completed the Impact of Event Scale Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS).
The IES-R score ranges from 0 (best) to 88 (worst) with a score of more than 22 indicating presence of PTSD-related symptoms of clinical concern. The HADS has separate subscales for anxiety and depression, with a score of 7 or greater on a 21-point scale indicating symptoms of anxiety or depression.
Family members also rated social supports on a scale from 0 (extremely limited) to 10 (extremely effective). Dr. Azoulay noted that social support is the subjective perception of the extent to which friends, mental health specialists, and others are available and helpful.
Investigators divided patients into two groups depending on whether or not the cause of ARDS was COVID-19. Causes other than COVID-19 mainly included community-acquired pneumonia and influenza.
The primary outcome was the prevalence of PTSD-related symptoms among family members. Secondary outcomes were the prevalence of anxiety and depression in family members.
The analysis included 303 family members of patients with COVID-19 ARDS and 214 family members of patients with non–COVID-19 ARDS. Almost half of the family members were spouses.
Those with family members with COVID-19 were younger than the non-COVID group (median age, 50 vs. 55 years). They were less frequently allowed to visit the ICU (35% vs. 88%) and more commonly received patient information by phone (84% vs. 20%).
Better strategies needed
Results showed PTSD symptoms were significantly more common in family members of patients with than without COVID-10 (35% vs. 19%; difference of 16%; 95% confidence interval, 8%-24%; P < .001).
Anxiety symptoms were significantly more common in the COVID-19 group (41% vs. 34%; difference of 8%; 95% CI, 0%-16%; P = .05), as were depression symptoms (31% vs. 18%; difference of 13%; 95% CI, 6%-21%; P < .001).
About 26% of the hospitalized relatives died. PTSD symptoms were more common among bereaved family members of patients who died from COVID-19 than of patients without COVID-19 (63% vs. 39%; difference of 24%; 95% CI, 7%-40%; P = .008).
In the COVID-19 group, significantly fewer family members reported having attended the funeral (77% vs. 91%, P = .04). This could be because of concerns over transmitting the virus, the investigators noted.
After adjustment for age, sex, and level of social support in a multivariable analysis, COVID-19 ARDS was significantly associated with increased risk for PTSD-related symptoms in family members (odds ratio, 2.05; 95% CI, 1.30-3.23; P =.002).
Other factors independently associated with PTSD symptoms were age, level of social support, and being male.
Factors associated with anxiety included having COVID-19 ARDS, age, being male, and level of social support. COVID-19 ARDS and level of social support were independently associated with depression.
Although isolation measures were implemented to prevent viral transmission during the pandemic, severely restricting family members from interacting with their sick loved ones in the ICU is “very destructive [and] deeply distressing,” said Dr. Azoulay. “It’s almost cruel.”
Fear may be at the heart of the “psycho-trauma” experienced by family members, he said.
“I would say one of the main sources is fear of getting infected, fear of abandoning family members, fear of leaving the kids alone without any support, and fear of infecting others,” he added.
Health care providers should develop strategies to better communicate with family members, who also feel a lot of guilt when they’re unable to be with their sick loved ones, said Dr. Azoulay.
‘Element of fear’
Commenting on the findings for this news organization, O. Joseph Bienvenu, MD, PhD, professor of psychiatry and behavioral sciences at Johns Hopkins Medicine, Baltimore, called the study “solid” and noted the lead author is “a well-recognized clinical researcher.”
It was “remarkable” that investigators were able to include a control group of family members of patients with ARDS not due to COVID-19, added Dr. Bienvenu, who was not involved with the research.
“It sounds like the bottom line is COVID adds an additional element of fear in loved ones,” he said.
Dr. Bienvenu added this fits with his own clinical experience – and noted that some COVID-19 follow-up clinics now include family members in their assessments and care.
“I think this study nicely illustrates the utility of this,” he concluded.
The study received funding from the French Ministry of Health. Dr. Azoulay reported receipt of personal fees from lectures from Pfizer, Gilead, Baxter, and Alexion, and institutional research grants from Merck Sharp and Dohme, Pfizer, Baxter, and Alexion. Dr. Bienvenu has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The pandemic has significantly affected the mental health of family members of patients with COVID-19, including high rates of posttraumatic stress disorder (PTSD), anxiety, and depression, new research suggests.
They also had a higher prevalence of depression and anxiety symptoms.
The results illustrate how the mental health of families has been adversely affected by strict isolation measures instituted at the height of the COVID pandemic, lead author Elie Azoulay, MD, PhD, professor of medicine at Diderot University and director of the Medical Intensive Care Unit, Saint Louis Hospital, Paris, told this news organization.
Such restrictions were unnecessary, Dr. Azoulay noted, adding that everyone, including health care professionals, benefits when families are allowed to interact with their loved ones in the ICU.
He added the study findings also emphasize the importance of social supports.
“We need to develop and really increase what we can do for family members” of patients staying in the ICU, said Dr. Azoulay.
The findings were published online Feb. 18 in JAMA.
Twenty-three ICUs in France
The study included adult family members of patients admitted with ARDS to 23 ICUs in France from January to October 2020.
Patients had a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) of less than 300, and bilateral opacities on chest radiography not fully explained by cardiac failure or fluid overload.
Two trained clinical psychologists interviewed family members and patients by telephone a median of 112 days after ICU discharge. During this interview, participants completed the Impact of Event Scale Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS).
The IES-R score ranges from 0 (best) to 88 (worst) with a score of more than 22 indicating presence of PTSD-related symptoms of clinical concern. The HADS has separate subscales for anxiety and depression, with a score of 7 or greater on a 21-point scale indicating symptoms of anxiety or depression.
Family members also rated social supports on a scale from 0 (extremely limited) to 10 (extremely effective). Dr. Azoulay noted that social support is the subjective perception of the extent to which friends, mental health specialists, and others are available and helpful.
Investigators divided patients into two groups depending on whether or not the cause of ARDS was COVID-19. Causes other than COVID-19 mainly included community-acquired pneumonia and influenza.
The primary outcome was the prevalence of PTSD-related symptoms among family members. Secondary outcomes were the prevalence of anxiety and depression in family members.
The analysis included 303 family members of patients with COVID-19 ARDS and 214 family members of patients with non–COVID-19 ARDS. Almost half of the family members were spouses.
Those with family members with COVID-19 were younger than the non-COVID group (median age, 50 vs. 55 years). They were less frequently allowed to visit the ICU (35% vs. 88%) and more commonly received patient information by phone (84% vs. 20%).
Better strategies needed
Results showed PTSD symptoms were significantly more common in family members of patients with than without COVID-10 (35% vs. 19%; difference of 16%; 95% confidence interval, 8%-24%; P < .001).
Anxiety symptoms were significantly more common in the COVID-19 group (41% vs. 34%; difference of 8%; 95% CI, 0%-16%; P = .05), as were depression symptoms (31% vs. 18%; difference of 13%; 95% CI, 6%-21%; P < .001).
About 26% of the hospitalized relatives died. PTSD symptoms were more common among bereaved family members of patients who died from COVID-19 than of patients without COVID-19 (63% vs. 39%; difference of 24%; 95% CI, 7%-40%; P = .008).
In the COVID-19 group, significantly fewer family members reported having attended the funeral (77% vs. 91%, P = .04). This could be because of concerns over transmitting the virus, the investigators noted.
After adjustment for age, sex, and level of social support in a multivariable analysis, COVID-19 ARDS was significantly associated with increased risk for PTSD-related symptoms in family members (odds ratio, 2.05; 95% CI, 1.30-3.23; P =.002).
Other factors independently associated with PTSD symptoms were age, level of social support, and being male.
Factors associated with anxiety included having COVID-19 ARDS, age, being male, and level of social support. COVID-19 ARDS and level of social support were independently associated with depression.
Although isolation measures were implemented to prevent viral transmission during the pandemic, severely restricting family members from interacting with their sick loved ones in the ICU is “very destructive [and] deeply distressing,” said Dr. Azoulay. “It’s almost cruel.”
Fear may be at the heart of the “psycho-trauma” experienced by family members, he said.
“I would say one of the main sources is fear of getting infected, fear of abandoning family members, fear of leaving the kids alone without any support, and fear of infecting others,” he added.
Health care providers should develop strategies to better communicate with family members, who also feel a lot of guilt when they’re unable to be with their sick loved ones, said Dr. Azoulay.
‘Element of fear’
Commenting on the findings for this news organization, O. Joseph Bienvenu, MD, PhD, professor of psychiatry and behavioral sciences at Johns Hopkins Medicine, Baltimore, called the study “solid” and noted the lead author is “a well-recognized clinical researcher.”
It was “remarkable” that investigators were able to include a control group of family members of patients with ARDS not due to COVID-19, added Dr. Bienvenu, who was not involved with the research.
“It sounds like the bottom line is COVID adds an additional element of fear in loved ones,” he said.
Dr. Bienvenu added this fits with his own clinical experience – and noted that some COVID-19 follow-up clinics now include family members in their assessments and care.
“I think this study nicely illustrates the utility of this,” he concluded.
The study received funding from the French Ministry of Health. Dr. Azoulay reported receipt of personal fees from lectures from Pfizer, Gilead, Baxter, and Alexion, and institutional research grants from Merck Sharp and Dohme, Pfizer, Baxter, and Alexion. Dr. Bienvenu has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA
More evidence links MI to cognitive decline over time
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Stroke risk is highest right after COVID infection
, new research shows.
The study among Medicare beneficiaries with COVID-19 also showed that stroke risk is higher for relatively young older adults, those aged 65 to 74 years, and those without a history of stroke.
The study highlights the impact COVID-19 has on the cardiovascular system, said study author Quanhe Yang, PhD, senior scientist, Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta.
“Clinicians and patients should understand that stroke might be one of the very important clinical consequences of COVID-19.”
The study was presented during the hybrid International Stroke Conference held in New Orleans and online. The meeting was presented by the American Stroke Association, a division of the American Heart Association.
Stroke is the fifth leading cause of death in the U.S. As an increasing number of people become infected with COVID-19, “it’s important to determine if there’s a relationship between COVID and the risk of stroke,” said Dr. Yang.
Findings from prior research examining the link between stroke and COVID-19 have been inconsistent, he noted. Some studies found an association while others did not, and in still others, the association was not as strong as expected.
Many factors may contribute to these inconsistent findings, said Dr. Yang, including differences in study design, inclusion criteria, comparison groups, sample sizes, and countries where the research was carried out. Dr. Yang pointed out that many of these studies were done in the early stages of the pandemic or didn’t include older adults, the population most at risk for stroke.
The current study included 19,553 Medicare beneficiaries aged 65 years and older diagnosed with COVID-19 and hospitalized with acute ischemic stroke. The median age at diagnosis of COVID-19 was 80.5 years, 57.5% were women, and more than 75% were non-Hispanic Whites.
To ensure the stroke occurred after a COVID infection, researchers used a self-controlled case series study design, a “within person” comparison between the risk period and the control period.
They divided the study period (Jan. 1, 2019 to Feb. 28, 2021) into the exposure or stroke risk periods after the COVID diagnosis (0-3 days; 4-7 days; 8-15 days; and 15-28 days) and control periods.
Strokes that occurred 7 days before or 28 days after a COVID diagnosis served as a control period. “Any stroke that occurred outside the risk window is in the control period,” explained Dr. Yang.
He added that the control period provides a baseline. “Without COVID-19, this is what I would expect” in terms of the number of strokes.
To estimate the incidence rate ratio (IRR), investigators compared the incidence of acute ischemic stroke in the various risk periods with control periods.
The IRR was 10.97 (95% confidence interval, 10.30-11.68) at 0-3 days. The risk then quickly declined but stayed higher than the control period. The IRRs were: 1.59 (95% CI, 1.35-1.87) at 4-7 days; 1.23 (95% CI, 1.07-1.41) at 8-14 days; and 1.06 (95% CI, 0.95-1.18) at 15-28 days.
The temporary increase in stroke risk early after an infection isn’t novel; the pattern has been observed with influenza, respiratory infections, and shingles, said Dr. Yang. “But COVID-19 appears to be particularly risky.”
Although the mechanism driving the early increased stroke risk isn’t fully understood, it’s likely tied to an “exaggerated inflammatory response,” said Dr. Yang. This can trigger the cascade of events setting the stage for a stroke – a hypercoagulation state leading to the formation of blood clots that then block arteries to the brain, he said.
It’s also possible the infection directly affects endothelial cells, leading to rupture of plaque, again blocking arteries and raising stroke risks, added Dr. Yang.
The association was stronger among younger beneficiaries, aged 65 to 74 years, compared with those 85 years and older, a finding Dr. Yang said was somewhat surprising. But he noted other studies have found stroke patients with COVID are younger than stroke patients without COVID – by some 5 to 6 years.
“If COVID-19 disproportionately affects younger patients, that may explain the stronger association,” said Dr. Yang. “Stroke risk increases tremendously with age, so if you’re a younger age, your baseline stroke risk is lower.”
The association was also stronger among beneficiaries without a history of stroke. Again, this could be related to the stronger association among younger patients who are less likely to have suffered a stroke. The association was largely consistent across sex and race/ethnicities.
Dr. Yang stressed that the findings need to be confirmed with further studies.
The study was carried out before widespread use of vaccinations in the U.S. Once those data are available, Dr. Yang and his colleagues plan to determine if vaccinations modify the association between COVID-19 and stroke risk.
The new results contribute to the mounting evidence that a COVID-19 infection “can actually affect multiple human organs structurally or functionally in addition to the impact on [the] respiratory system,” said Dr. Yang.
Some dates of COVID-19 diagnoses may be incorrect due to limited test availability, particularly early in the pandemic. Another limitation of the study was possible misclassification from the use of Medicare real-time preliminary claims.
In a provided statement, Louise D. McCullough, MD, PhD, chair of the ISC 2022 and professor and chair of neurology, McGovern Medical School, University of Texas Health Science Center at Houston, noted that the study focused on older adults because it was examining Medicare beneficiaries.
“But everyone is likely at risk for stroke after COVID,” she said. “Any infection is linked to stroke risk, probably because any infection will cause inflammation, and inflammation can cause clots or thrombus, which is the cause of stroke.”
There was no outside funding for the study. No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
, new research shows.
The study among Medicare beneficiaries with COVID-19 also showed that stroke risk is higher for relatively young older adults, those aged 65 to 74 years, and those without a history of stroke.
The study highlights the impact COVID-19 has on the cardiovascular system, said study author Quanhe Yang, PhD, senior scientist, Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta.
“Clinicians and patients should understand that stroke might be one of the very important clinical consequences of COVID-19.”
The study was presented during the hybrid International Stroke Conference held in New Orleans and online. The meeting was presented by the American Stroke Association, a division of the American Heart Association.
Stroke is the fifth leading cause of death in the U.S. As an increasing number of people become infected with COVID-19, “it’s important to determine if there’s a relationship between COVID and the risk of stroke,” said Dr. Yang.
Findings from prior research examining the link between stroke and COVID-19 have been inconsistent, he noted. Some studies found an association while others did not, and in still others, the association was not as strong as expected.
Many factors may contribute to these inconsistent findings, said Dr. Yang, including differences in study design, inclusion criteria, comparison groups, sample sizes, and countries where the research was carried out. Dr. Yang pointed out that many of these studies were done in the early stages of the pandemic or didn’t include older adults, the population most at risk for stroke.
The current study included 19,553 Medicare beneficiaries aged 65 years and older diagnosed with COVID-19 and hospitalized with acute ischemic stroke. The median age at diagnosis of COVID-19 was 80.5 years, 57.5% were women, and more than 75% were non-Hispanic Whites.
To ensure the stroke occurred after a COVID infection, researchers used a self-controlled case series study design, a “within person” comparison between the risk period and the control period.
They divided the study period (Jan. 1, 2019 to Feb. 28, 2021) into the exposure or stroke risk periods after the COVID diagnosis (0-3 days; 4-7 days; 8-15 days; and 15-28 days) and control periods.
Strokes that occurred 7 days before or 28 days after a COVID diagnosis served as a control period. “Any stroke that occurred outside the risk window is in the control period,” explained Dr. Yang.
He added that the control period provides a baseline. “Without COVID-19, this is what I would expect” in terms of the number of strokes.
To estimate the incidence rate ratio (IRR), investigators compared the incidence of acute ischemic stroke in the various risk periods with control periods.
The IRR was 10.97 (95% confidence interval, 10.30-11.68) at 0-3 days. The risk then quickly declined but stayed higher than the control period. The IRRs were: 1.59 (95% CI, 1.35-1.87) at 4-7 days; 1.23 (95% CI, 1.07-1.41) at 8-14 days; and 1.06 (95% CI, 0.95-1.18) at 15-28 days.
The temporary increase in stroke risk early after an infection isn’t novel; the pattern has been observed with influenza, respiratory infections, and shingles, said Dr. Yang. “But COVID-19 appears to be particularly risky.”
Although the mechanism driving the early increased stroke risk isn’t fully understood, it’s likely tied to an “exaggerated inflammatory response,” said Dr. Yang. This can trigger the cascade of events setting the stage for a stroke – a hypercoagulation state leading to the formation of blood clots that then block arteries to the brain, he said.
It’s also possible the infection directly affects endothelial cells, leading to rupture of plaque, again blocking arteries and raising stroke risks, added Dr. Yang.
The association was stronger among younger beneficiaries, aged 65 to 74 years, compared with those 85 years and older, a finding Dr. Yang said was somewhat surprising. But he noted other studies have found stroke patients with COVID are younger than stroke patients without COVID – by some 5 to 6 years.
“If COVID-19 disproportionately affects younger patients, that may explain the stronger association,” said Dr. Yang. “Stroke risk increases tremendously with age, so if you’re a younger age, your baseline stroke risk is lower.”
The association was also stronger among beneficiaries without a history of stroke. Again, this could be related to the stronger association among younger patients who are less likely to have suffered a stroke. The association was largely consistent across sex and race/ethnicities.
Dr. Yang stressed that the findings need to be confirmed with further studies.
The study was carried out before widespread use of vaccinations in the U.S. Once those data are available, Dr. Yang and his colleagues plan to determine if vaccinations modify the association between COVID-19 and stroke risk.
The new results contribute to the mounting evidence that a COVID-19 infection “can actually affect multiple human organs structurally or functionally in addition to the impact on [the] respiratory system,” said Dr. Yang.
Some dates of COVID-19 diagnoses may be incorrect due to limited test availability, particularly early in the pandemic. Another limitation of the study was possible misclassification from the use of Medicare real-time preliminary claims.
In a provided statement, Louise D. McCullough, MD, PhD, chair of the ISC 2022 and professor and chair of neurology, McGovern Medical School, University of Texas Health Science Center at Houston, noted that the study focused on older adults because it was examining Medicare beneficiaries.
“But everyone is likely at risk for stroke after COVID,” she said. “Any infection is linked to stroke risk, probably because any infection will cause inflammation, and inflammation can cause clots or thrombus, which is the cause of stroke.”
There was no outside funding for the study. No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
, new research shows.
The study among Medicare beneficiaries with COVID-19 also showed that stroke risk is higher for relatively young older adults, those aged 65 to 74 years, and those without a history of stroke.
The study highlights the impact COVID-19 has on the cardiovascular system, said study author Quanhe Yang, PhD, senior scientist, Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta.
“Clinicians and patients should understand that stroke might be one of the very important clinical consequences of COVID-19.”
The study was presented during the hybrid International Stroke Conference held in New Orleans and online. The meeting was presented by the American Stroke Association, a division of the American Heart Association.
Stroke is the fifth leading cause of death in the U.S. As an increasing number of people become infected with COVID-19, “it’s important to determine if there’s a relationship between COVID and the risk of stroke,” said Dr. Yang.
Findings from prior research examining the link between stroke and COVID-19 have been inconsistent, he noted. Some studies found an association while others did not, and in still others, the association was not as strong as expected.
Many factors may contribute to these inconsistent findings, said Dr. Yang, including differences in study design, inclusion criteria, comparison groups, sample sizes, and countries where the research was carried out. Dr. Yang pointed out that many of these studies were done in the early stages of the pandemic or didn’t include older adults, the population most at risk for stroke.
The current study included 19,553 Medicare beneficiaries aged 65 years and older diagnosed with COVID-19 and hospitalized with acute ischemic stroke. The median age at diagnosis of COVID-19 was 80.5 years, 57.5% were women, and more than 75% were non-Hispanic Whites.
To ensure the stroke occurred after a COVID infection, researchers used a self-controlled case series study design, a “within person” comparison between the risk period and the control period.
They divided the study period (Jan. 1, 2019 to Feb. 28, 2021) into the exposure or stroke risk periods after the COVID diagnosis (0-3 days; 4-7 days; 8-15 days; and 15-28 days) and control periods.
Strokes that occurred 7 days before or 28 days after a COVID diagnosis served as a control period. “Any stroke that occurred outside the risk window is in the control period,” explained Dr. Yang.
He added that the control period provides a baseline. “Without COVID-19, this is what I would expect” in terms of the number of strokes.
To estimate the incidence rate ratio (IRR), investigators compared the incidence of acute ischemic stroke in the various risk periods with control periods.
The IRR was 10.97 (95% confidence interval, 10.30-11.68) at 0-3 days. The risk then quickly declined but stayed higher than the control period. The IRRs were: 1.59 (95% CI, 1.35-1.87) at 4-7 days; 1.23 (95% CI, 1.07-1.41) at 8-14 days; and 1.06 (95% CI, 0.95-1.18) at 15-28 days.
The temporary increase in stroke risk early after an infection isn’t novel; the pattern has been observed with influenza, respiratory infections, and shingles, said Dr. Yang. “But COVID-19 appears to be particularly risky.”
Although the mechanism driving the early increased stroke risk isn’t fully understood, it’s likely tied to an “exaggerated inflammatory response,” said Dr. Yang. This can trigger the cascade of events setting the stage for a stroke – a hypercoagulation state leading to the formation of blood clots that then block arteries to the brain, he said.
It’s also possible the infection directly affects endothelial cells, leading to rupture of plaque, again blocking arteries and raising stroke risks, added Dr. Yang.
The association was stronger among younger beneficiaries, aged 65 to 74 years, compared with those 85 years and older, a finding Dr. Yang said was somewhat surprising. But he noted other studies have found stroke patients with COVID are younger than stroke patients without COVID – by some 5 to 6 years.
“If COVID-19 disproportionately affects younger patients, that may explain the stronger association,” said Dr. Yang. “Stroke risk increases tremendously with age, so if you’re a younger age, your baseline stroke risk is lower.”
The association was also stronger among beneficiaries without a history of stroke. Again, this could be related to the stronger association among younger patients who are less likely to have suffered a stroke. The association was largely consistent across sex and race/ethnicities.
Dr. Yang stressed that the findings need to be confirmed with further studies.
The study was carried out before widespread use of vaccinations in the U.S. Once those data are available, Dr. Yang and his colleagues plan to determine if vaccinations modify the association between COVID-19 and stroke risk.
The new results contribute to the mounting evidence that a COVID-19 infection “can actually affect multiple human organs structurally or functionally in addition to the impact on [the] respiratory system,” said Dr. Yang.
Some dates of COVID-19 diagnoses may be incorrect due to limited test availability, particularly early in the pandemic. Another limitation of the study was possible misclassification from the use of Medicare real-time preliminary claims.
In a provided statement, Louise D. McCullough, MD, PhD, chair of the ISC 2022 and professor and chair of neurology, McGovern Medical School, University of Texas Health Science Center at Houston, noted that the study focused on older adults because it was examining Medicare beneficiaries.
“But everyone is likely at risk for stroke after COVID,” she said. “Any infection is linked to stroke risk, probably because any infection will cause inflammation, and inflammation can cause clots or thrombus, which is the cause of stroke.”
There was no outside funding for the study. No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Tenecteplase for stroke linked to reduced ICH risk
preliminary results from a large, multicenter registry study suggest.
“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.
“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.
The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.
Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”
Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”
However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.
Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.
The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.
Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).
Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.
They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.
Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”
In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).
Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”
An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)
The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.
“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.
He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”
Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.
Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.
“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.
Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”
Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.
A version of this article first appeared on Medscape.com.
preliminary results from a large, multicenter registry study suggest.
“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.
“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.
The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.
Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”
Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”
However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.
Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.
The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.
Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).
Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.
They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.
Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”
In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).
Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”
An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)
The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.
“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.
He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”
Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.
Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.
“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.
Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”
Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.
A version of this article first appeared on Medscape.com.
preliminary results from a large, multicenter registry study suggest.
“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.
“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.
The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.
Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”
Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”
However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.
Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.
The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.
Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).
Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.
They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.
Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”
In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).
Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”
An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)
The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.
“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.
He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”
Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.
Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.
“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.
Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”
Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Is mild cognitive impairment reversible?
new research shows.
The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.
In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.
“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.
The findings were published online Feb. 4, 2022, in the journal Neurology.
Highly educated cohort
As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.
The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.
Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.
Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.
The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.
“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.
The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
Dementia not inevitable
Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.
This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.
“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.
The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.
Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.
However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.
Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.
There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
Language skills key
Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).
In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.
“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.
The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).
These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.
“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
Research implications
Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.
“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.
The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research shows.
The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.
In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.
“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.
The findings were published online Feb. 4, 2022, in the journal Neurology.
Highly educated cohort
As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.
The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.
Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.
Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.
The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.
“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.
The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
Dementia not inevitable
Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.
This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.
“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.
The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.
Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.
However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.
Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.
There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
Language skills key
Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).
In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.
“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.
The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).
These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.
“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
Research implications
Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.
“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.
The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research shows.
The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.
In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.
“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.
The findings were published online Feb. 4, 2022, in the journal Neurology.
Highly educated cohort
As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.
The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.
Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.
Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.
The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.
“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.
The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
Dementia not inevitable
Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.
This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.
“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.
The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.
Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.
However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.
Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.
There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
Language skills key
Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).
In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.
“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.
The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).
These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.
“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
Research implications
Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.
“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.
The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New stroke risk score developed for COVID patients
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Strep infection and tics in children: new data
Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.
The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.
Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.
The study was published online Feb. 2 in Neurology.
Ongoing controversy
Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.
There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.
This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.
The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.
The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.
Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”
Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.
The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
More common in boys
Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.
The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.
They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.
At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.
During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.
Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.
However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).
This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.
Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
Other pathogens?
Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.
“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”
Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.
It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.
Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.
“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”
The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”
The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.
The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.
Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.
The study was published online Feb. 2 in Neurology.
Ongoing controversy
Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.
There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.
This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.
The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.
The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.
Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”
Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.
The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
More common in boys
Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.
The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.
They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.
At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.
During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.
Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.
However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).
This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.
Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
Other pathogens?
Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.
“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”
Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.
It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.
Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.
“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”
The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”
The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.
The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.
Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.
The study was published online Feb. 2 in Neurology.
Ongoing controversy
Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.
There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.
This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.
The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.
The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.
Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”
Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.
The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
More common in boys
Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.
The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.
They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.
At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.
During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.
Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.
However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).
This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.
Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
Other pathogens?
Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.
“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”
Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.
It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.
Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.
“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”
The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”
The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Chronic marijuana use linked to recurrent stroke
, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.
“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”
The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.
Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”
Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.
Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.
Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.
Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.
A higher rate of recurrent stroke
For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.
They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.
The analysis did not include those who were considered in remission from cannabis use disorder.
Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).
After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).
Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.
But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.
“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”
He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”
Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
Hypothesis-generating research
The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.
As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.
The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”
A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.
Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.
A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.
He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”
The study received no outside funding. The authors report no relevant disclosures.
A version of this article first appeared on Medscape.com.
, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.
“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”
The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.
Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”
Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.
Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.
Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.
Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.
A higher rate of recurrent stroke
For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.
They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.
The analysis did not include those who were considered in remission from cannabis use disorder.
Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).
After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).
Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.
But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.
“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”
He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”
Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
Hypothesis-generating research
The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.
As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.
The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”
A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.
Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.
A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.
He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”
The study received no outside funding. The authors report no relevant disclosures.
A version of this article first appeared on Medscape.com.
, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.
“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”
The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.
Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”
Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.
Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.
Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.
Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.
A higher rate of recurrent stroke
For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.
They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.
The analysis did not include those who were considered in remission from cannabis use disorder.
Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).
After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).
Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.
But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.
“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”
He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”
Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
Hypothesis-generating research
The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.
As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.
The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”
A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.
Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.
A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.
He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”
The study received no outside funding. The authors report no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Motor function restored in three men after complete paralysis from spinal cord injury
(SCI), new research shows.
The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.
“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.
The study was published online Feb. 7, 2022, in Nature Medicine.
More rapid, precise, effective
SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.
However, these approaches aren’t yet ready for prime time.
In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.
But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”
To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.
In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.
They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.
All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.
A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.
The men can select different activity-based programs from a tablet that sends signals to the implanted device.
Personalized approach
Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.
“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.
At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.
“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”
Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”
Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.
Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.
A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.
Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.
The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.
“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.
ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
A ‘huge step forward’
Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”
Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”
There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”
However, he questioned the researchers’ use of the word “walking.”
“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.
In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.
The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(SCI), new research shows.
The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.
“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.
The study was published online Feb. 7, 2022, in Nature Medicine.
More rapid, precise, effective
SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.
However, these approaches aren’t yet ready for prime time.
In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.
But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”
To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.
In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.
They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.
All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.
A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.
The men can select different activity-based programs from a tablet that sends signals to the implanted device.
Personalized approach
Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.
“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.
At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.
“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”
Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”
Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.
Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.
A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.
Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.
The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.
“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.
ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
A ‘huge step forward’
Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”
Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”
There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”
However, he questioned the researchers’ use of the word “walking.”
“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.
In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.
The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(SCI), new research shows.
The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.
“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.
The study was published online Feb. 7, 2022, in Nature Medicine.
More rapid, precise, effective
SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.
However, these approaches aren’t yet ready for prime time.
In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.
But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”
To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.
In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.
They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.
All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.
A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.
The men can select different activity-based programs from a tablet that sends signals to the implanted device.
Personalized approach
Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.
“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.
At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.
“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”
Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”
Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.
Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.
A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.
Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.
The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.
“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.
ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
A ‘huge step forward’
Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”
Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”
There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”
However, he questioned the researchers’ use of the word “walking.”
“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.
In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.
The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
Drinking a risk factor for epilepsy?
but more research is needed before any definitive conclusions can be drawn.
Results of an updated meta-analysis are consistent with those of a previous meta-analysis but contrast with some prior cohort studies.
“Further large cohort studies of the general population are required to assert a definite causal relationship between alcohol consumption and epilepsy and to identify a potential threshold,” Yun Hak Kim, MD, PhD, departments of biomedical informatics and anatomy, Pusan (South Korea) National University, said in a press release.
The study was published online Jan. 11, 2022, in Drug and Alcohol Dependence.
Conflicting findings
Much of the research into the impact of alcohol on epilepsy risk has focused on provoked seizures related to alcohol intoxication or withdrawal, but few studies have investigated the effect of alcohol on unprovoked seizures. In addition, the research in this area has been conflicting.
A 2010 meta-analysis that included six case-control studies showed alcohol users had an increased risk of unprovoked seizure or epilepsy with a pooled relative risk of 2.19 (95% confidence interval, 1.82-2.63). This analysis also showed a dose-dependent relationship with relative risks increasing with more grams of alcohol consumed daily.
However, some recent large cohort studies showed that moderate alcohol consumption was associated with a lower risk of epilepsy.
The updated meta-analysis included eight studies – three cohort studies not included in the previous meta-analysis and five case-control studies.
The study excluded two case-control studies included in the previous meta-analysis. One of these studies used duplicated data, and the other included epilepsy patients and did not present results of subgroup analysis for patients experiencing their first seizure.
Results of the new analysis showed the pooled odds ratio for newly diagnosed epilepsy was 1.70 (95% CI, 1.16-2.49) in alcohol users versus nondrinkers.
A dose-response analysis of case-control studies carried out using the cubic spline analysis showed a significant positive dose-response relationship. A dose-response graph showed a steep increase in risk above about 150 g/day and 250 g/day of alcohol consumption.
However, a subgroup analysis showed that epilepsy risk was only found in the case-control studies. In fact, two of the three cohort studies showed that alcohol consumption was associated with a lower risk of epilepsy, although this was not significant.
Cohort studies often include more control subjects and longer follow-up periods and are less prone to bias, such as selection and recall biases, the investigators noted.
“Therefore, cohort studies usually provide a stronger association between exposure and disease than case-control studies, despite having limitations for diseases with low incidence levels,” they wrote.
More research needed
The researchers added that most case-control studies included in the new meta-analysis assessed alcohol consumption only in the 6 months prior to the onset of seizures. Research shows it usually takes heavy drinkers 5 or more years to develop repetitive unprovoked seizures.
“Considering these temporal relationships and differences in study design, alcohol may not actually increase the risk of epilepsy, as seen in our subgroup analysis for cohort studies,” the investigators wrote.
They noted that the cohort studies in the meta-analysis were variously limited to young women, elderly patients, and post–subdural hematoma patients. “This limitation makes it difficult to confirm or generalize the results of the subgroup analysis.”
To resolve this “discrepancy,” further large cohort studies of the general population over a longer period are needed, the investigators wrote.
Examining the risk of bias within studies, the authors evaluated three cohort studies as “good” quality. Of the case-control studies, they rated two as “good,” one as “fair,” and two as “poor.”
For primary prevention, an assessment of the risk of alcohol consumption in various clinical situations, such as the time relation of alcohol consumption with seizures, will be important, lead author Kyoung Nam Woo, department of neurology, Pusan National University, said in the release.
“To increase the applicability to the general population, future studies should be conducted in which the potential confounders such as age, sex, and smoking have been adjusted.”
Commenting on the study, Jacqueline French, MD, professor, New York University Comprehensive Epilepsy Center, echoed the authors in noting a number of weaknesses in the study.
The analysis was unable to exclude alcohol withdrawal seizures. Also, while some studies suggested a positive relationship, others suggested a negative relationship, she said. “The authors suggest further work is needed before a definitive determination is made, and I agree.”
The study received funding from the Medical Research Center Program, the Basic Science Research Program, and the Collaborative Genome Program for Fostering New Post-Genome Industry through a National Research Foundation of Korea grant funded by the Korean government. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
but more research is needed before any definitive conclusions can be drawn.
Results of an updated meta-analysis are consistent with those of a previous meta-analysis but contrast with some prior cohort studies.
“Further large cohort studies of the general population are required to assert a definite causal relationship between alcohol consumption and epilepsy and to identify a potential threshold,” Yun Hak Kim, MD, PhD, departments of biomedical informatics and anatomy, Pusan (South Korea) National University, said in a press release.
The study was published online Jan. 11, 2022, in Drug and Alcohol Dependence.
Conflicting findings
Much of the research into the impact of alcohol on epilepsy risk has focused on provoked seizures related to alcohol intoxication or withdrawal, but few studies have investigated the effect of alcohol on unprovoked seizures. In addition, the research in this area has been conflicting.
A 2010 meta-analysis that included six case-control studies showed alcohol users had an increased risk of unprovoked seizure or epilepsy with a pooled relative risk of 2.19 (95% confidence interval, 1.82-2.63). This analysis also showed a dose-dependent relationship with relative risks increasing with more grams of alcohol consumed daily.
However, some recent large cohort studies showed that moderate alcohol consumption was associated with a lower risk of epilepsy.
The updated meta-analysis included eight studies – three cohort studies not included in the previous meta-analysis and five case-control studies.
The study excluded two case-control studies included in the previous meta-analysis. One of these studies used duplicated data, and the other included epilepsy patients and did not present results of subgroup analysis for patients experiencing their first seizure.
Results of the new analysis showed the pooled odds ratio for newly diagnosed epilepsy was 1.70 (95% CI, 1.16-2.49) in alcohol users versus nondrinkers.
A dose-response analysis of case-control studies carried out using the cubic spline analysis showed a significant positive dose-response relationship. A dose-response graph showed a steep increase in risk above about 150 g/day and 250 g/day of alcohol consumption.
However, a subgroup analysis showed that epilepsy risk was only found in the case-control studies. In fact, two of the three cohort studies showed that alcohol consumption was associated with a lower risk of epilepsy, although this was not significant.
Cohort studies often include more control subjects and longer follow-up periods and are less prone to bias, such as selection and recall biases, the investigators noted.
“Therefore, cohort studies usually provide a stronger association between exposure and disease than case-control studies, despite having limitations for diseases with low incidence levels,” they wrote.
More research needed
The researchers added that most case-control studies included in the new meta-analysis assessed alcohol consumption only in the 6 months prior to the onset of seizures. Research shows it usually takes heavy drinkers 5 or more years to develop repetitive unprovoked seizures.
“Considering these temporal relationships and differences in study design, alcohol may not actually increase the risk of epilepsy, as seen in our subgroup analysis for cohort studies,” the investigators wrote.
They noted that the cohort studies in the meta-analysis were variously limited to young women, elderly patients, and post–subdural hematoma patients. “This limitation makes it difficult to confirm or generalize the results of the subgroup analysis.”
To resolve this “discrepancy,” further large cohort studies of the general population over a longer period are needed, the investigators wrote.
Examining the risk of bias within studies, the authors evaluated three cohort studies as “good” quality. Of the case-control studies, they rated two as “good,” one as “fair,” and two as “poor.”
For primary prevention, an assessment of the risk of alcohol consumption in various clinical situations, such as the time relation of alcohol consumption with seizures, will be important, lead author Kyoung Nam Woo, department of neurology, Pusan National University, said in the release.
“To increase the applicability to the general population, future studies should be conducted in which the potential confounders such as age, sex, and smoking have been adjusted.”
Commenting on the study, Jacqueline French, MD, professor, New York University Comprehensive Epilepsy Center, echoed the authors in noting a number of weaknesses in the study.
The analysis was unable to exclude alcohol withdrawal seizures. Also, while some studies suggested a positive relationship, others suggested a negative relationship, she said. “The authors suggest further work is needed before a definitive determination is made, and I agree.”
The study received funding from the Medical Research Center Program, the Basic Science Research Program, and the Collaborative Genome Program for Fostering New Post-Genome Industry through a National Research Foundation of Korea grant funded by the Korean government. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
but more research is needed before any definitive conclusions can be drawn.
Results of an updated meta-analysis are consistent with those of a previous meta-analysis but contrast with some prior cohort studies.
“Further large cohort studies of the general population are required to assert a definite causal relationship between alcohol consumption and epilepsy and to identify a potential threshold,” Yun Hak Kim, MD, PhD, departments of biomedical informatics and anatomy, Pusan (South Korea) National University, said in a press release.
The study was published online Jan. 11, 2022, in Drug and Alcohol Dependence.
Conflicting findings
Much of the research into the impact of alcohol on epilepsy risk has focused on provoked seizures related to alcohol intoxication or withdrawal, but few studies have investigated the effect of alcohol on unprovoked seizures. In addition, the research in this area has been conflicting.
A 2010 meta-analysis that included six case-control studies showed alcohol users had an increased risk of unprovoked seizure or epilepsy with a pooled relative risk of 2.19 (95% confidence interval, 1.82-2.63). This analysis also showed a dose-dependent relationship with relative risks increasing with more grams of alcohol consumed daily.
However, some recent large cohort studies showed that moderate alcohol consumption was associated with a lower risk of epilepsy.
The updated meta-analysis included eight studies – three cohort studies not included in the previous meta-analysis and five case-control studies.
The study excluded two case-control studies included in the previous meta-analysis. One of these studies used duplicated data, and the other included epilepsy patients and did not present results of subgroup analysis for patients experiencing their first seizure.
Results of the new analysis showed the pooled odds ratio for newly diagnosed epilepsy was 1.70 (95% CI, 1.16-2.49) in alcohol users versus nondrinkers.
A dose-response analysis of case-control studies carried out using the cubic spline analysis showed a significant positive dose-response relationship. A dose-response graph showed a steep increase in risk above about 150 g/day and 250 g/day of alcohol consumption.
However, a subgroup analysis showed that epilepsy risk was only found in the case-control studies. In fact, two of the three cohort studies showed that alcohol consumption was associated with a lower risk of epilepsy, although this was not significant.
Cohort studies often include more control subjects and longer follow-up periods and are less prone to bias, such as selection and recall biases, the investigators noted.
“Therefore, cohort studies usually provide a stronger association between exposure and disease than case-control studies, despite having limitations for diseases with low incidence levels,” they wrote.
More research needed
The researchers added that most case-control studies included in the new meta-analysis assessed alcohol consumption only in the 6 months prior to the onset of seizures. Research shows it usually takes heavy drinkers 5 or more years to develop repetitive unprovoked seizures.
“Considering these temporal relationships and differences in study design, alcohol may not actually increase the risk of epilepsy, as seen in our subgroup analysis for cohort studies,” the investigators wrote.
They noted that the cohort studies in the meta-analysis were variously limited to young women, elderly patients, and post–subdural hematoma patients. “This limitation makes it difficult to confirm or generalize the results of the subgroup analysis.”
To resolve this “discrepancy,” further large cohort studies of the general population over a longer period are needed, the investigators wrote.
Examining the risk of bias within studies, the authors evaluated three cohort studies as “good” quality. Of the case-control studies, they rated two as “good,” one as “fair,” and two as “poor.”
For primary prevention, an assessment of the risk of alcohol consumption in various clinical situations, such as the time relation of alcohol consumption with seizures, will be important, lead author Kyoung Nam Woo, department of neurology, Pusan National University, said in the release.
“To increase the applicability to the general population, future studies should be conducted in which the potential confounders such as age, sex, and smoking have been adjusted.”
Commenting on the study, Jacqueline French, MD, professor, New York University Comprehensive Epilepsy Center, echoed the authors in noting a number of weaknesses in the study.
The analysis was unable to exclude alcohol withdrawal seizures. Also, while some studies suggested a positive relationship, others suggested a negative relationship, she said. “The authors suggest further work is needed before a definitive determination is made, and I agree.”
The study received funding from the Medical Research Center Program, the Basic Science Research Program, and the Collaborative Genome Program for Fostering New Post-Genome Industry through a National Research Foundation of Korea grant funded by the Korean government. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ALCOHOL DEPENDENCE