Neurology

Adjunctive oral prednisone appears to significantly reduce cluster headache attacks, new research shows. Results of the multicenter, randomized, double-blind trial show that patients who received the steroid had 25% fewer attacks in the first week of therapy, compared with their counterparts who received placebo.

In addition, more than a third of patients in the prednisone group were pain free, and for almost half, headache frequency was reduced by at least 50% at day 7 of treatment.

These findings provide clear evidence that prednisone, in conjunction with the use of verapamil, is effective in cluster headache, said lead author Mark Obermann, MD, director, Center for Neurology, Asklepios Hospitals Seesen (Germany), and associate professor, University of Duisburg-Essen (Germany).

The key message, he added, is that all patients with cluster headache should receive prednisone at the start of an episode.

The study was published online Nov. 24 in the Lancet Neurology.
 

‘Suicide headaches’

Cluster headaches are intense unilateral attacks of facial and head pain. They last 15-180 minutes and predominantly affect men. They are accompanied by trigeminal autonomic symptoms and are extremely painful. “They’re referred to as ‘suicide headaches’ because the pain is so severe that patients often report they think about killing themselves to get rid of the pain,” said Dr. Obermann.

The cause is unclear, although there is some evidence that the hypothalamus is involved. The headaches sometimes follow a “strict circadian pattern,” said Dr. Obermann. He noted that the attacks might occur over a few weeks or months and then not return for months or even years.

An estimated 1 in 1,000 people experience cluster headache, but the condition is underrecognized, and research is scarce and poorly funded. Previous research does show that the calcium channel blocker verapamil, which is used to treat high blood pressure, is effective in cluster headache. However, it takes about 14 days to work and has to be slowly titrated because of cardiac side effects, said Dr. Obermann. For these reasons, international guidelines recommend initiating short-term preventive treatment with corticosteroids to suppress, or at least lessen, cluster headache attacks until long-term prevention is effective.

Although some clinicians treat cluster headaches with corticosteroids, others don’t because of a lack of evidence that shows they are effective. “There’s no evidence whatsoever on what the correct dose is or whether it helps at all. This is the gap we wanted to close,” said Dr. Obermann.

The study included 116 adult patients with cluster headache from 10 centers who were experiencing a cluster headache episode and were not taking prophylactic medication.

The trial only included patients who had an attack within 30 days of their current episode. The investigators included this restriction to reduce the possibility of spontaneous remission, which is “a big problem” in cluster headache trials, he said. To confirm that episodes were cluster headache attacks, patients were also required to have moderate to severe pain, indicated by a score of at least 5 on a numerical rating scale in which 0 indicates no pain and 10 indicates the worse imaginable pain.

Participants were allowed to use treatments for acute attack, but these therapies were limited to triptans, high-flow oxygen, intranasal lidocaine, ergotamine, and oral analgesics.
 

Debilitating pain

Patients were randomly assigned to receive oral prednisone (n = 53) or placebo (n = 56). The study groups were matched with respect to demographic and clinical characteristics. Prednisone was initiated at 100 mg/d for 5 days and was then tapered by 20 mg every 3 days in the active-treatment group. All patients also received oral verapamil at a starting dose of 40 mg three times per day. The dose was increased every 3 days by 40 mg to a maximum of 360 mg/d.

All participants received pantoprazole 20 mg to prevent the gastric side effects of prednisone. An attack was defined as a unilateral headache of moderate to severe intensity. The study lasted 28 days.

The study’s primary outcome was the mean number of cluster headache attacks during the first week of treatment with prednisone versus placebo.

The mean number of attacks during the first week of treatment was 7.1 in the prednisone group and 9.5 in the placebo group, for a difference of –2.4 attacks (95% confidence interval, –4.8 to –0.03; P = .002). “This might not sound like much,” but reducing the number of daily attacks from, say, eight to six “really makes a difference because the attacks are so painful,” said Dr. Obermann.

The prednisone group also came out on top for a number secondary outcomes. After the first 7 days, attacks ceased in 35% of the prednisone group versus 7% in the placebo group.
 

‘Clear evidence’ of efficacy

About 49% of patients who took prednisone reported a reduction of at least 50% in attack frequency at day 7. By comparison, 15% of patients who received placebo reported such a reduction. The number of cluster attacks at day 28 was less in the prednisone group than in the patients who received placebo.

With respect to treatment effect, the difference between prednisone and placebo gradually lessened over time “in parallel to the verapamil dose reaching its therapeutic effect,” the investigators noted. “Therefore, attack frequency reduction slowly converged between groups,” they added.

The study results provide “clear evidence” and should reassure clinicians that short-term prednisone early in a cluster headache attack is effective, said Dr. Obermann.

Adverse events, which included headache, palpitations, dizziness, and nausea, were as expected and were similar in the two groups. There were only two severe adverse events, both of which occurred in participants in the placebo group.

Dr. Obermann said the investigators were surprised that so many patients in the study were taking analgesics. “Analgesics don’t work in cluster headache; they just don’t work in this kind of pain.”

He noted that prednisone exposure of study patients spanned only 19 days and amounted to only 1,100 mg, which he believes is safe.

The prednisone dose used in the study is “what most clinicians use in clinical practice,” although there have been reports of success using 500 mg of IV prednisone over 5 days, said Dr. Obermann. He added that it would be “interesting to see if 50 mg would be just as good” as a starting dose.

Potential limitations of the study include the fact that the majority of participants were White, so the findings may not be generalizable to other populations.
 

Long-awaited results

In an accompanying editorial, Anne Ducros, MD, PhD, professor of neurology and director of the Headache Center, Montpellier (France) University Hospital, said the study provides “strong and long-awaited evidence supporting the use of oral steroids as a transitional treatment option.”

The trial “raises many topics for future research,” one of which is the long-term safety of prednisone for patients with cluster headache, said Dr. Ducros. She noted that use of high-dose steroids once or twice a year for 15 years or more “has the potential for severe systemic toxic effects,” such as corticosteroid-induced osteonecrosis of the femoral head.

Other questions about corticosteroid use for patients with cluster headache remain. These include understanding whether these agents provide better efficacy than occipital nerve injections and determining the optimal verapamil regimen, she noted.

In addition, the risk for oral steroid misuse needs to be studied, she said. She noted that drug misuse is common among patients with cluster headache.

Despite these questions, the results of this new study “provide an important step forward for patients with cluster headache, for whom safe and effective transitional therapies are much needed,” Dr. Ducros wrote.


Dr. Obermann has received fees from Sanofi, Biogen, Novartis, Teva Pharmaceuticals, and Eli Lilly and grants from Allergan and Heel Pharmaceuticals outside of this work. Dr. Ducros has received fees from Amgen, Novartis, Teva, and Eli Lilly; grants from the Programme Hospitalier de Recherche Clinique and from the Appel d’Offre Interne of Montpellier University Hospital; and nonfinancial support from SOS Oxygene.

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

Adjunctive oral prednisone appears to significantly reduce cluster headache attacks, new research shows. Results of the multicenter, randomized, double-blind trial show that patients who received the steroid had 25% fewer attacks in the first week of therapy, compared with their counterparts who received placebo.

In addition, more than a third of patients in the prednisone group were pain free, and for almost half, headache frequency was reduced by at least 50% at day 7 of treatment.

These findings provide clear evidence that prednisone, in conjunction with the use of verapamil, is effective in cluster headache, said lead author Mark Obermann, MD, director, Center for Neurology, Asklepios Hospitals Seesen (Germany), and associate professor, University of Duisburg-Essen (Germany).

The key message, he added, is that all patients with cluster headache should receive prednisone at the start of an episode.

The study was published online Nov. 24 in the Lancet Neurology.
 

‘Suicide headaches’

Cluster headaches are intense unilateral attacks of facial and head pain. They last 15-180 minutes and predominantly affect men. They are accompanied by trigeminal autonomic symptoms and are extremely painful. “They’re referred to as ‘suicide headaches’ because the pain is so severe that patients often report they think about killing themselves to get rid of the pain,” said Dr. Obermann.

The cause is unclear, although there is some evidence that the hypothalamus is involved. The headaches sometimes follow a “strict circadian pattern,” said Dr. Obermann. He noted that the attacks might occur over a few weeks or months and then not return for months or even years.

An estimated 1 in 1,000 people experience cluster headache, but the condition is underrecognized, and research is scarce and poorly funded. Previous research does show that the calcium channel blocker verapamil, which is used to treat high blood pressure, is effective in cluster headache. However, it takes about 14 days to work and has to be slowly titrated because of cardiac side effects, said Dr. Obermann. For these reasons, international guidelines recommend initiating short-term preventive treatment with corticosteroids to suppress, or at least lessen, cluster headache attacks until long-term prevention is effective.

Although some clinicians treat cluster headaches with corticosteroids, others don’t because of a lack of evidence that shows they are effective. “There’s no evidence whatsoever on what the correct dose is or whether it helps at all. This is the gap we wanted to close,” said Dr. Obermann.

The study included 116 adult patients with cluster headache from 10 centers who were experiencing a cluster headache episode and were not taking prophylactic medication.

The trial only included patients who had an attack within 30 days of their current episode. The investigators included this restriction to reduce the possibility of spontaneous remission, which is “a big problem” in cluster headache trials, he said. To confirm that episodes were cluster headache attacks, patients were also required to have moderate to severe pain, indicated by a score of at least 5 on a numerical rating scale in which 0 indicates no pain and 10 indicates the worse imaginable pain.

Participants were allowed to use treatments for acute attack, but these therapies were limited to triptans, high-flow oxygen, intranasal lidocaine, ergotamine, and oral analgesics.
 

Debilitating pain

Patients were randomly assigned to receive oral prednisone (n = 53) or placebo (n = 56). The study groups were matched with respect to demographic and clinical characteristics. Prednisone was initiated at 100 mg/d for 5 days and was then tapered by 20 mg every 3 days in the active-treatment group. All patients also received oral verapamil at a starting dose of 40 mg three times per day. The dose was increased every 3 days by 40 mg to a maximum of 360 mg/d.

All participants received pantoprazole 20 mg to prevent the gastric side effects of prednisone. An attack was defined as a unilateral headache of moderate to severe intensity. The study lasted 28 days.

The study’s primary outcome was the mean number of cluster headache attacks during the first week of treatment with prednisone versus placebo.

The mean number of attacks during the first week of treatment was 7.1 in the prednisone group and 9.5 in the placebo group, for a difference of –2.4 attacks (95% confidence interval, –4.8 to –0.03; P = .002). “This might not sound like much,” but reducing the number of daily attacks from, say, eight to six “really makes a difference because the attacks are so painful,” said Dr. Obermann.

The prednisone group also came out on top for a number secondary outcomes. After the first 7 days, attacks ceased in 35% of the prednisone group versus 7% in the placebo group.
 

‘Clear evidence’ of efficacy

About 49% of patients who took prednisone reported a reduction of at least 50% in attack frequency at day 7. By comparison, 15% of patients who received placebo reported such a reduction. The number of cluster attacks at day 28 was less in the prednisone group than in the patients who received placebo.

With respect to treatment effect, the difference between prednisone and placebo gradually lessened over time “in parallel to the verapamil dose reaching its therapeutic effect,” the investigators noted. “Therefore, attack frequency reduction slowly converged between groups,” they added.

The study results provide “clear evidence” and should reassure clinicians that short-term prednisone early in a cluster headache attack is effective, said Dr. Obermann.

Adverse events, which included headache, palpitations, dizziness, and nausea, were as expected and were similar in the two groups. There were only two severe adverse events, both of which occurred in participants in the placebo group.

Dr. Obermann said the investigators were surprised that so many patients in the study were taking analgesics. “Analgesics don’t work in cluster headache; they just don’t work in this kind of pain.”

He noted that prednisone exposure of study patients spanned only 19 days and amounted to only 1,100 mg, which he believes is safe.

The prednisone dose used in the study is “what most clinicians use in clinical practice,” although there have been reports of success using 500 mg of IV prednisone over 5 days, said Dr. Obermann. He added that it would be “interesting to see if 50 mg would be just as good” as a starting dose.

Potential limitations of the study include the fact that the majority of participants were White, so the findings may not be generalizable to other populations.
 

Long-awaited results

In an accompanying editorial, Anne Ducros, MD, PhD, professor of neurology and director of the Headache Center, Montpellier (France) University Hospital, said the study provides “strong and long-awaited evidence supporting the use of oral steroids as a transitional treatment option.”

The trial “raises many topics for future research,” one of which is the long-term safety of prednisone for patients with cluster headache, said Dr. Ducros. She noted that use of high-dose steroids once or twice a year for 15 years or more “has the potential for severe systemic toxic effects,” such as corticosteroid-induced osteonecrosis of the femoral head.

Other questions about corticosteroid use for patients with cluster headache remain. These include understanding whether these agents provide better efficacy than occipital nerve injections and determining the optimal verapamil regimen, she noted.

In addition, the risk for oral steroid misuse needs to be studied, she said. She noted that drug misuse is common among patients with cluster headache.

Despite these questions, the results of this new study “provide an important step forward for patients with cluster headache, for whom safe and effective transitional therapies are much needed,” Dr. Ducros wrote.


Dr. Obermann has received fees from Sanofi, Biogen, Novartis, Teva Pharmaceuticals, and Eli Lilly and grants from Allergan and Heel Pharmaceuticals outside of this work. Dr. Ducros has received fees from Amgen, Novartis, Teva, and Eli Lilly; grants from the Programme Hospitalier de Recherche Clinique and from the Appel d’Offre Interne of Montpellier University Hospital; and nonfinancial support from SOS Oxygene.

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

Adjunctive oral prednisone appears to significantly reduce cluster headache attacks, new research shows. Results of the multicenter, randomized, double-blind trial show that patients who received the steroid had 25% fewer attacks in the first week of therapy, compared with their counterparts who received placebo.

In addition, more than a third of patients in the prednisone group were pain free, and for almost half, headache frequency was reduced by at least 50% at day 7 of treatment.

These findings provide clear evidence that prednisone, in conjunction with the use of verapamil, is effective in cluster headache, said lead author Mark Obermann, MD, director, Center for Neurology, Asklepios Hospitals Seesen (Germany), and associate professor, University of Duisburg-Essen (Germany).

The key message, he added, is that all patients with cluster headache should receive prednisone at the start of an episode.

The study was published online Nov. 24 in the Lancet Neurology.
 

‘Suicide headaches’

Cluster headaches are intense unilateral attacks of facial and head pain. They last 15-180 minutes and predominantly affect men. They are accompanied by trigeminal autonomic symptoms and are extremely painful. “They’re referred to as ‘suicide headaches’ because the pain is so severe that patients often report they think about killing themselves to get rid of the pain,” said Dr. Obermann.

The cause is unclear, although there is some evidence that the hypothalamus is involved. The headaches sometimes follow a “strict circadian pattern,” said Dr. Obermann. He noted that the attacks might occur over a few weeks or months and then not return for months or even years.

An estimated 1 in 1,000 people experience cluster headache, but the condition is underrecognized, and research is scarce and poorly funded. Previous research does show that the calcium channel blocker verapamil, which is used to treat high blood pressure, is effective in cluster headache. However, it takes about 14 days to work and has to be slowly titrated because of cardiac side effects, said Dr. Obermann. For these reasons, international guidelines recommend initiating short-term preventive treatment with corticosteroids to suppress, or at least lessen, cluster headache attacks until long-term prevention is effective.

Although some clinicians treat cluster headaches with corticosteroids, others don’t because of a lack of evidence that shows they are effective. “There’s no evidence whatsoever on what the correct dose is or whether it helps at all. This is the gap we wanted to close,” said Dr. Obermann.

The study included 116 adult patients with cluster headache from 10 centers who were experiencing a cluster headache episode and were not taking prophylactic medication.

The trial only included patients who had an attack within 30 days of their current episode. The investigators included this restriction to reduce the possibility of spontaneous remission, which is “a big problem” in cluster headache trials, he said. To confirm that episodes were cluster headache attacks, patients were also required to have moderate to severe pain, indicated by a score of at least 5 on a numerical rating scale in which 0 indicates no pain and 10 indicates the worse imaginable pain.

Participants were allowed to use treatments for acute attack, but these therapies were limited to triptans, high-flow oxygen, intranasal lidocaine, ergotamine, and oral analgesics.
 

Debilitating pain

Patients were randomly assigned to receive oral prednisone (n = 53) or placebo (n = 56). The study groups were matched with respect to demographic and clinical characteristics. Prednisone was initiated at 100 mg/d for 5 days and was then tapered by 20 mg every 3 days in the active-treatment group. All patients also received oral verapamil at a starting dose of 40 mg three times per day. The dose was increased every 3 days by 40 mg to a maximum of 360 mg/d.

All participants received pantoprazole 20 mg to prevent the gastric side effects of prednisone. An attack was defined as a unilateral headache of moderate to severe intensity. The study lasted 28 days.

The study’s primary outcome was the mean number of cluster headache attacks during the first week of treatment with prednisone versus placebo.

The mean number of attacks during the first week of treatment was 7.1 in the prednisone group and 9.5 in the placebo group, for a difference of –2.4 attacks (95% confidence interval, –4.8 to –0.03; P = .002). “This might not sound like much,” but reducing the number of daily attacks from, say, eight to six “really makes a difference because the attacks are so painful,” said Dr. Obermann.

The prednisone group also came out on top for a number secondary outcomes. After the first 7 days, attacks ceased in 35% of the prednisone group versus 7% in the placebo group.
 

‘Clear evidence’ of efficacy

About 49% of patients who took prednisone reported a reduction of at least 50% in attack frequency at day 7. By comparison, 15% of patients who received placebo reported such a reduction. The number of cluster attacks at day 28 was less in the prednisone group than in the patients who received placebo.

With respect to treatment effect, the difference between prednisone and placebo gradually lessened over time “in parallel to the verapamil dose reaching its therapeutic effect,” the investigators noted. “Therefore, attack frequency reduction slowly converged between groups,” they added.

The study results provide “clear evidence” and should reassure clinicians that short-term prednisone early in a cluster headache attack is effective, said Dr. Obermann.

Adverse events, which included headache, palpitations, dizziness, and nausea, were as expected and were similar in the two groups. There were only two severe adverse events, both of which occurred in participants in the placebo group.

Dr. Obermann said the investigators were surprised that so many patients in the study were taking analgesics. “Analgesics don’t work in cluster headache; they just don’t work in this kind of pain.”

He noted that prednisone exposure of study patients spanned only 19 days and amounted to only 1,100 mg, which he believes is safe.

The prednisone dose used in the study is “what most clinicians use in clinical practice,” although there have been reports of success using 500 mg of IV prednisone over 5 days, said Dr. Obermann. He added that it would be “interesting to see if 50 mg would be just as good” as a starting dose.

Potential limitations of the study include the fact that the majority of participants were White, so the findings may not be generalizable to other populations.
 

Long-awaited results

In an accompanying editorial, Anne Ducros, MD, PhD, professor of neurology and director of the Headache Center, Montpellier (France) University Hospital, said the study provides “strong and long-awaited evidence supporting the use of oral steroids as a transitional treatment option.”

The trial “raises many topics for future research,” one of which is the long-term safety of prednisone for patients with cluster headache, said Dr. Ducros. She noted that use of high-dose steroids once or twice a year for 15 years or more “has the potential for severe systemic toxic effects,” such as corticosteroid-induced osteonecrosis of the femoral head.

Other questions about corticosteroid use for patients with cluster headache remain. These include understanding whether these agents provide better efficacy than occipital nerve injections and determining the optimal verapamil regimen, she noted.

In addition, the risk for oral steroid misuse needs to be studied, she said. She noted that drug misuse is common among patients with cluster headache.

Despite these questions, the results of this new study “provide an important step forward for patients with cluster headache, for whom safe and effective transitional therapies are much needed,” Dr. Ducros wrote.


Dr. Obermann has received fees from Sanofi, Biogen, Novartis, Teva Pharmaceuticals, and Eli Lilly and grants from Allergan and Heel Pharmaceuticals outside of this work. Dr. Ducros has received fees from Amgen, Novartis, Teva, and Eli Lilly; grants from the Programme Hospitalier de Recherche Clinique and from the Appel d’Offre Interne of Montpellier University Hospital; and nonfinancial support from SOS Oxygene.

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

There is “compelling” evidence of the harmful effects of alcohol on the brain. The greatest risk occurs during three periods of life that are marked by dynamic brain changes, say researchers from Australia and the United Kingdom.

alenkadr/Thinkstock

The three periods are:

• Gestation (conception to birth), which is characterized by extensive production, migration, and differentiation of neurons, as well as substantial apoptosis.
• Later adolescence (aged 15-19 years), a period marked by synaptic pruning and increased axonal myelination.
• Older adulthood (aged 65 and beyond), a period associated with brain atrophy. Changes accelerate after age 65, largely driven by decreases in neuron size and reductions in the number of dendritic spines and synapses.

These changes in neurocircuitry could increase sensitivity to the neurotoxic effects of alcohol, Louise Mewton, PhD, of the Center for Healthy Brain Aging, University of New South Wales, Sydney, and colleagues said.

“A life course perspective on brain health supports the formulation of policy and public health interventions to reduce alcohol use and misuse at all ages,” they wrote in an editorial published online Dec. 4 in The BMJ.
 

Worrisome trends

Research has shown that globally about 10% of pregnant women drink alcohol. In European countries, the rates are much higher than the global average.

Heavy drinking during gestation can cause fetal alcohol spectrum disorder, which is associated with widespread reductions in brain volume and cognitive impairment.

Even low or moderate alcohol consumption during pregnancy is significantly associated with poorer psychological and behavioral outcomes in children, the investigators noted.

In adolescence, more than 20% of 15- to 19-year-olds in European and other high-income countries report at least occasional binge drinking, which is linked to reduced brain volume, poorer white matter development, and deficits in a range of cognitive functions, they added.

In a recent study of older adults, alcohol use disorders emerged as one of the strongest modifiable risk factors for dementia (particularly early-onset dementia), compared with other established risk factors such as high blood pressure and smoking.

Alcohol use disorders are relatively rare in older adults, but even moderate drinking during midlife has been linked to “small but significant” brain volume loss, the authors said.

Dr. Mewton and colleagues said demographic trends may compound the effect of alcohol use on brain health.

They noted that women are now just as likely as men to drink alcohol and suffer alcohol-related problems. Global consumption is forecast to increase further in the next decade.

Although the effects of the COVID-19 pandemic on alcohol intake and related harms remain unclear, alcohol use has increased in the long term after other major public health crises, they added.

Given the data, Dr. Mewton and colleagues called for “an integrated approach” to reducing the harms of alcohol intake at all ages.

“Population-based interventions such as guidelines on low-risk drinking, alcohol pricing policies, and lower drink driving limits need to be accompanied by the development of training and care pathways that consider the human brain at risk throughout life,” they concluded.

The authors have disclosed no relevant financial relationships.
 

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

There is “compelling” evidence of the harmful effects of alcohol on the brain. The greatest risk occurs during three periods of life that are marked by dynamic brain changes, say researchers from Australia and the United Kingdom.

alenkadr/Thinkstock

The three periods are:

• Gestation (conception to birth), which is characterized by extensive production, migration, and differentiation of neurons, as well as substantial apoptosis.
• Later adolescence (aged 15-19 years), a period marked by synaptic pruning and increased axonal myelination.
• Older adulthood (aged 65 and beyond), a period associated with brain atrophy. Changes accelerate after age 65, largely driven by decreases in neuron size and reductions in the number of dendritic spines and synapses.

These changes in neurocircuitry could increase sensitivity to the neurotoxic effects of alcohol, Louise Mewton, PhD, of the Center for Healthy Brain Aging, University of New South Wales, Sydney, and colleagues said.

“A life course perspective on brain health supports the formulation of policy and public health interventions to reduce alcohol use and misuse at all ages,” they wrote in an editorial published online Dec. 4 in The BMJ.
 

Worrisome trends

Research has shown that globally about 10% of pregnant women drink alcohol. In European countries, the rates are much higher than the global average.

Heavy drinking during gestation can cause fetal alcohol spectrum disorder, which is associated with widespread reductions in brain volume and cognitive impairment.

Even low or moderate alcohol consumption during pregnancy is significantly associated with poorer psychological and behavioral outcomes in children, the investigators noted.

In adolescence, more than 20% of 15- to 19-year-olds in European and other high-income countries report at least occasional binge drinking, which is linked to reduced brain volume, poorer white matter development, and deficits in a range of cognitive functions, they added.

In a recent study of older adults, alcohol use disorders emerged as one of the strongest modifiable risk factors for dementia (particularly early-onset dementia), compared with other established risk factors such as high blood pressure and smoking.

Alcohol use disorders are relatively rare in older adults, but even moderate drinking during midlife has been linked to “small but significant” brain volume loss, the authors said.

Dr. Mewton and colleagues said demographic trends may compound the effect of alcohol use on brain health.

They noted that women are now just as likely as men to drink alcohol and suffer alcohol-related problems. Global consumption is forecast to increase further in the next decade.

Although the effects of the COVID-19 pandemic on alcohol intake and related harms remain unclear, alcohol use has increased in the long term after other major public health crises, they added.

Given the data, Dr. Mewton and colleagues called for “an integrated approach” to reducing the harms of alcohol intake at all ages.

“Population-based interventions such as guidelines on low-risk drinking, alcohol pricing policies, and lower drink driving limits need to be accompanied by the development of training and care pathways that consider the human brain at risk throughout life,” they concluded.

The authors have disclosed no relevant financial relationships.
 

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

There is “compelling” evidence of the harmful effects of alcohol on the brain. The greatest risk occurs during three periods of life that are marked by dynamic brain changes, say researchers from Australia and the United Kingdom.

alenkadr/Thinkstock

The three periods are:

• Gestation (conception to birth), which is characterized by extensive production, migration, and differentiation of neurons, as well as substantial apoptosis.
• Later adolescence (aged 15-19 years), a period marked by synaptic pruning and increased axonal myelination.
• Older adulthood (aged 65 and beyond), a period associated with brain atrophy. Changes accelerate after age 65, largely driven by decreases in neuron size and reductions in the number of dendritic spines and synapses.

These changes in neurocircuitry could increase sensitivity to the neurotoxic effects of alcohol, Louise Mewton, PhD, of the Center for Healthy Brain Aging, University of New South Wales, Sydney, and colleagues said.

“A life course perspective on brain health supports the formulation of policy and public health interventions to reduce alcohol use and misuse at all ages,” they wrote in an editorial published online Dec. 4 in The BMJ.
 

Worrisome trends

Research has shown that globally about 10% of pregnant women drink alcohol. In European countries, the rates are much higher than the global average.

Heavy drinking during gestation can cause fetal alcohol spectrum disorder, which is associated with widespread reductions in brain volume and cognitive impairment.

Even low or moderate alcohol consumption during pregnancy is significantly associated with poorer psychological and behavioral outcomes in children, the investigators noted.

In adolescence, more than 20% of 15- to 19-year-olds in European and other high-income countries report at least occasional binge drinking, which is linked to reduced brain volume, poorer white matter development, and deficits in a range of cognitive functions, they added.

In a recent study of older adults, alcohol use disorders emerged as one of the strongest modifiable risk factors for dementia (particularly early-onset dementia), compared with other established risk factors such as high blood pressure and smoking.

Alcohol use disorders are relatively rare in older adults, but even moderate drinking during midlife has been linked to “small but significant” brain volume loss, the authors said.

Dr. Mewton and colleagues said demographic trends may compound the effect of alcohol use on brain health.

They noted that women are now just as likely as men to drink alcohol and suffer alcohol-related problems. Global consumption is forecast to increase further in the next decade.

Although the effects of the COVID-19 pandemic on alcohol intake and related harms remain unclear, alcohol use has increased in the long term after other major public health crises, they added.

Given the data, Dr. Mewton and colleagues called for “an integrated approach” to reducing the harms of alcohol intake at all ages.

“Population-based interventions such as guidelines on low-risk drinking, alcohol pricing policies, and lower drink driving limits need to be accompanied by the development of training and care pathways that consider the human brain at risk throughout life,” they concluded.

The authors have disclosed no relevant financial relationships.
 

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

Cases of poisoning – intentional and unintentional – from ingestion of alcohol-based hand sanitizer have soared during the COVID-19 pandemic.

In the United Kingdom alone, alcohol-based hand sanitizer poisonings reported to the National Poisons Information Service jumped 157% – from 155 between January 1 and September 16, 2019, to 398 between Jan. 1 and Sept. 14, 2020, new research shows.

More needs to be done to protect those at risk of unintentional and intentional swallowing of alcohol-based hand sanitizer, including children, people with dementia/confusion, and those with mental health issues, according to Georgia Richards, DPhil student, Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford (England).

“If providers are supplying alcohol-based hand sanitizers in the community to reduce the spread of SARS-CoV-2, the contents should be supplied in lockable and automated dispensers to reduce contamination and improve safety,” Ms. Richards said in an interview.

The study was published online Dec. 1 in BMJ Evidence-Based Medicine.
 

European, U.S. poisoning rates soar

In the paper Ms. Richards described two deaths that occurred in hospitals in England.

In one case, a 30-year-old woman, detained in a psychiatric unit who received the antidepressant venlafaxine was found dead in her hospital bed with a container of hand-sanitizing gel beside her.

“The gel was readily accessible to patients on the ward from a communal dispenser, and patients were allowed to fill cups or other containers with it to keep in their rooms,” Ms. Richards reported.

A postmortem analysis found a high level of alcohol in her blood (214 mg of alcohol in 100 mL of blood). The medical cause of death was listed as “ingestion of alcohol and venlafaxine.” The coroner concluded that the combination of these substances suppressed the patient’s breathing, leading to her death.

The other case involved a 76-year-old man who unintentionally swallowed an unknown quantity of alcohol-based hand-sanitizing foam attached to the foot of his hospital bed.

The patient had a history of agitation and depression and was treated with antidepressants. He had become increasingly confused over the preceding 9 months, possibly because of vascular dementia.

His blood ethanol concentration was 463 mg/dL (100 mmol/L) initially and 354 mg/dL (77mmol/L) 10 hours later. He was admitted to the ICU, where he received lorazepam and haloperidol and treated with ventilation, with a plan to allow the alcohol to be naturally metabolized.

The patient developed complications and died 6 days later. The primary causes of death were bronchopneumonia and acute alcohol toxicity, secondary to acute delirium and coronary artery disease.

Since COVID-19 started, alcohol-based hand sanitizers are among the most sought-after commodities around the world. The volume of these products – now found in homes, hospitals, schools, workplaces, and elsewhere – “may be a cause for concern,” Ms. Richards wrote.

Yet, warnings about the toxicity and lethality of intentional or unintentional ingestion of these products have not been widely disseminated, she noted.

To reduce the risk of harm, Ms. Richards suggested educating the public and health care professionals, improving warning labels on products, and increasing the awareness and reporting of such exposures to public health authorities.

“While governments and public health authorities have successfully heightened our awareness of, and need for, better hand hygiene during the COVID-19 outbreak, they must also make the public aware of the potential harms and encourage the reporting of such harms to poisons information centers,” she noted.

Increases in alcohol-based hand sanitizer poisoning during the pandemic have also been reported in the United States.

The American Association of Poison Control Centers reports that data from the National Poison Data System show 32,892 hand sanitizer exposure cases reported to the 55 U.S. poison control centers from Jan. 1 to Nov. 15, 2020 – an increase of 73%, compared with the same time period during the previous year.
 

An increase in self-harm

Weighing in on this issue, Robert Bassett, DO, associate medical director of the Poison Control Center at Children’s Hospital of Philadelphia, said in an interview that “cleaning agents and disinfectants have been around for eons and their potential for toxicity hasn’t changed.

“Now with COVID, and this hypervigilance when it comes to cleanliness, there is increased access and the exposure risk has gone up,” he said.

“One of the sad casualties of an overstressed health care system and a globally depressed environment is worsening behavioral health emergencies and, as part of that, the risk of self-harm goes up,” Dr. Bassett added.

“The consensus is that there has been an exacerbation of behavioral health emergencies and behavioral health needs since COVID started and hand sanitizers are readily accessible to someone who may be looking to self-harm,” he said.

This research had no specific funding. Ms. Richards is the editorial registrar of BMJ Evidence Based Medicine and is developing a website to track preventable deaths. Dr. Bassett disclosed no relevant financial relationships.

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

Cases of poisoning – intentional and unintentional – from ingestion of alcohol-based hand sanitizer have soared during the COVID-19 pandemic.

In the United Kingdom alone, alcohol-based hand sanitizer poisonings reported to the National Poisons Information Service jumped 157% – from 155 between January 1 and September 16, 2019, to 398 between Jan. 1 and Sept. 14, 2020, new research shows.

More needs to be done to protect those at risk of unintentional and intentional swallowing of alcohol-based hand sanitizer, including children, people with dementia/confusion, and those with mental health issues, according to Georgia Richards, DPhil student, Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford (England).

“If providers are supplying alcohol-based hand sanitizers in the community to reduce the spread of SARS-CoV-2, the contents should be supplied in lockable and automated dispensers to reduce contamination and improve safety,” Ms. Richards said in an interview.

The study was published online Dec. 1 in BMJ Evidence-Based Medicine.
 

European, U.S. poisoning rates soar

In the paper Ms. Richards described two deaths that occurred in hospitals in England.

In one case, a 30-year-old woman, detained in a psychiatric unit who received the antidepressant venlafaxine was found dead in her hospital bed with a container of hand-sanitizing gel beside her.

“The gel was readily accessible to patients on the ward from a communal dispenser, and patients were allowed to fill cups or other containers with it to keep in their rooms,” Ms. Richards reported.

A postmortem analysis found a high level of alcohol in her blood (214 mg of alcohol in 100 mL of blood). The medical cause of death was listed as “ingestion of alcohol and venlafaxine.” The coroner concluded that the combination of these substances suppressed the patient’s breathing, leading to her death.

The other case involved a 76-year-old man who unintentionally swallowed an unknown quantity of alcohol-based hand-sanitizing foam attached to the foot of his hospital bed.

The patient had a history of agitation and depression and was treated with antidepressants. He had become increasingly confused over the preceding 9 months, possibly because of vascular dementia.

His blood ethanol concentration was 463 mg/dL (100 mmol/L) initially and 354 mg/dL (77mmol/L) 10 hours later. He was admitted to the ICU, where he received lorazepam and haloperidol and treated with ventilation, with a plan to allow the alcohol to be naturally metabolized.

The patient developed complications and died 6 days later. The primary causes of death were bronchopneumonia and acute alcohol toxicity, secondary to acute delirium and coronary artery disease.

Since COVID-19 started, alcohol-based hand sanitizers are among the most sought-after commodities around the world. The volume of these products – now found in homes, hospitals, schools, workplaces, and elsewhere – “may be a cause for concern,” Ms. Richards wrote.

Yet, warnings about the toxicity and lethality of intentional or unintentional ingestion of these products have not been widely disseminated, she noted.

To reduce the risk of harm, Ms. Richards suggested educating the public and health care professionals, improving warning labels on products, and increasing the awareness and reporting of such exposures to public health authorities.

“While governments and public health authorities have successfully heightened our awareness of, and need for, better hand hygiene during the COVID-19 outbreak, they must also make the public aware of the potential harms and encourage the reporting of such harms to poisons information centers,” she noted.

Increases in alcohol-based hand sanitizer poisoning during the pandemic have also been reported in the United States.

The American Association of Poison Control Centers reports that data from the National Poison Data System show 32,892 hand sanitizer exposure cases reported to the 55 U.S. poison control centers from Jan. 1 to Nov. 15, 2020 – an increase of 73%, compared with the same time period during the previous year.
 

An increase in self-harm

Weighing in on this issue, Robert Bassett, DO, associate medical director of the Poison Control Center at Children’s Hospital of Philadelphia, said in an interview that “cleaning agents and disinfectants have been around for eons and their potential for toxicity hasn’t changed.

“Now with COVID, and this hypervigilance when it comes to cleanliness, there is increased access and the exposure risk has gone up,” he said.

“One of the sad casualties of an overstressed health care system and a globally depressed environment is worsening behavioral health emergencies and, as part of that, the risk of self-harm goes up,” Dr. Bassett added.

“The consensus is that there has been an exacerbation of behavioral health emergencies and behavioral health needs since COVID started and hand sanitizers are readily accessible to someone who may be looking to self-harm,” he said.

This research had no specific funding. Ms. Richards is the editorial registrar of BMJ Evidence Based Medicine and is developing a website to track preventable deaths. Dr. Bassett disclosed no relevant financial relationships.

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

Cases of poisoning – intentional and unintentional – from ingestion of alcohol-based hand sanitizer have soared during the COVID-19 pandemic.

In the United Kingdom alone, alcohol-based hand sanitizer poisonings reported to the National Poisons Information Service jumped 157% – from 155 between January 1 and September 16, 2019, to 398 between Jan. 1 and Sept. 14, 2020, new research shows.

More needs to be done to protect those at risk of unintentional and intentional swallowing of alcohol-based hand sanitizer, including children, people with dementia/confusion, and those with mental health issues, according to Georgia Richards, DPhil student, Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford (England).

“If providers are supplying alcohol-based hand sanitizers in the community to reduce the spread of SARS-CoV-2, the contents should be supplied in lockable and automated dispensers to reduce contamination and improve safety,” Ms. Richards said in an interview.

The study was published online Dec. 1 in BMJ Evidence-Based Medicine.
 

European, U.S. poisoning rates soar

In the paper Ms. Richards described two deaths that occurred in hospitals in England.

In one case, a 30-year-old woman, detained in a psychiatric unit who received the antidepressant venlafaxine was found dead in her hospital bed with a container of hand-sanitizing gel beside her.

“The gel was readily accessible to patients on the ward from a communal dispenser, and patients were allowed to fill cups or other containers with it to keep in their rooms,” Ms. Richards reported.

A postmortem analysis found a high level of alcohol in her blood (214 mg of alcohol in 100 mL of blood). The medical cause of death was listed as “ingestion of alcohol and venlafaxine.” The coroner concluded that the combination of these substances suppressed the patient’s breathing, leading to her death.

The other case involved a 76-year-old man who unintentionally swallowed an unknown quantity of alcohol-based hand-sanitizing foam attached to the foot of his hospital bed.

The patient had a history of agitation and depression and was treated with antidepressants. He had become increasingly confused over the preceding 9 months, possibly because of vascular dementia.

His blood ethanol concentration was 463 mg/dL (100 mmol/L) initially and 354 mg/dL (77mmol/L) 10 hours later. He was admitted to the ICU, where he received lorazepam and haloperidol and treated with ventilation, with a plan to allow the alcohol to be naturally metabolized.

The patient developed complications and died 6 days later. The primary causes of death were bronchopneumonia and acute alcohol toxicity, secondary to acute delirium and coronary artery disease.

Since COVID-19 started, alcohol-based hand sanitizers are among the most sought-after commodities around the world. The volume of these products – now found in homes, hospitals, schools, workplaces, and elsewhere – “may be a cause for concern,” Ms. Richards wrote.

Yet, warnings about the toxicity and lethality of intentional or unintentional ingestion of these products have not been widely disseminated, she noted.

To reduce the risk of harm, Ms. Richards suggested educating the public and health care professionals, improving warning labels on products, and increasing the awareness and reporting of such exposures to public health authorities.

“While governments and public health authorities have successfully heightened our awareness of, and need for, better hand hygiene during the COVID-19 outbreak, they must also make the public aware of the potential harms and encourage the reporting of such harms to poisons information centers,” she noted.

Increases in alcohol-based hand sanitizer poisoning during the pandemic have also been reported in the United States.

The American Association of Poison Control Centers reports that data from the National Poison Data System show 32,892 hand sanitizer exposure cases reported to the 55 U.S. poison control centers from Jan. 1 to Nov. 15, 2020 – an increase of 73%, compared with the same time period during the previous year.
 

An increase in self-harm

Weighing in on this issue, Robert Bassett, DO, associate medical director of the Poison Control Center at Children’s Hospital of Philadelphia, said in an interview that “cleaning agents and disinfectants have been around for eons and their potential for toxicity hasn’t changed.

“Now with COVID, and this hypervigilance when it comes to cleanliness, there is increased access and the exposure risk has gone up,” he said.

“One of the sad casualties of an overstressed health care system and a globally depressed environment is worsening behavioral health emergencies and, as part of that, the risk of self-harm goes up,” Dr. Bassett added.

“The consensus is that there has been an exacerbation of behavioral health emergencies and behavioral health needs since COVID started and hand sanitizers are readily accessible to someone who may be looking to self-harm,” he said.

This research had no specific funding. Ms. Richards is the editorial registrar of BMJ Evidence Based Medicine and is developing a website to track preventable deaths. Dr. Bassett disclosed no relevant financial relationships.

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

The National Board of Physicians and Surgeons (NBPAS) has announced that they are recertifying United Council of Neurologic Subspecialties (UCNS) diplomates as of Nov. 1, 2020. Recertification will include physicians who were initially board certified with UCNS in the subspecialties of autonomic disorders, behavioral neurology and neuropsychiatry, clinical neuromuscular pathology, geriatric neurology, headache medicine, neurocritical care, neuroimaging, and neuro-oncology.

In 2020, UCNS transitioned to a new continuous-certification (C-cert) model that requires its diplomates to pay an annual fee of $175 and complete a 25-question online quiz based on preselected journal articles with an 80% passing grade. In a press release outlining the details of the new C-cert program, UCNS said that diplomates began the transition last year by “attesting they have participated in subspecialty-specific continuing medical education (CME) requirements from the time their most recent certificate was issued through 2019.” Diplomates have a 2-year window, which began in 2019, to meet these transitional CME requirements and complete an attestation statement before their certification lapses. “Diplomates with a status of ‘meeting requirements’ will be issued a replacement certificate that shows their original certification date and will reflect there is no expiration date after they pay the first annual C-cert fee in 2020,” UCNS said in the press release.

“It is unfortunate that despite requests from diplomates and other stakeholders, UCNS has decided to impose new requirements and additional fees on diplomates who have unexpired certificates based on passing an examination that granted a 10-year certification,” Paul G. Mathew, MD, assistant professor of neurology at Harvard Medical School in Boston and Director of Legislative Affairs at NBPAS, said in an interview. “A one-size-fits-all approach for learning with preselected articles is not ideal, and physicians should be able to choose CME and other learning activities that best suit their individual interests and practice.”

The added requirements and fees have caused some UCNS diplomates to consider letting their certification lapse, Dr. Mathew said, but the NBPAS decision offers them a new path to recertification. “Many physicians who would have otherwise let their certification lapse and would no longer be considered board certified in headache medicine and other UCNS subspecialties will now have the option to recertify with NBPAS,” he said.

NBPAS was formed in 2014 in response to controversial American Board of Medical Specialties Maintenance of Certification (MOC) programs. NBPAS recertifies diplomates of all specialties and subspecialties offered by the ABMS and its member boards, including board certification in neurology and neurologic subspecialties offered by the American Board of Psychiatry and Neurology.

Board recertification with NBPAS requires an unrestricted license to practice medicine in the United States, an initial certification with ABPN, the American Osteopathic Association, and/or UCNS, a medical staff appointment/membership in good standing, active hospital privileges based on specialty, and 50 hours of relevant CME credits every 2 years.

“Although MOC compliance is not required for licensure, the vast majority of insurance carriers in the United States require to some extent that their physicians be MOC compliant. As such, the ABMS has a monopoly in that a physician cannot practice medicine without complying with MOC,” Dr. Mathew said. “That’s very gradually changing.”

So far, 13 states have passed legislation limiting ABMS MOC compliance as a requirement for credentialing or licensure, and 136 healthcare institutions have recognized NBPAS as a pathway for physician credentialing, according to an NBPAS press release.
 

Changing the rules

Alan Rapoport, MD, was asked to comment on the recertification situtaion. Dr. Rapoport is clinical professor of neurology at UCLA and the Editor in Chief of Neurology Reviews. “As Dr. Mathew aptly states, it is unfortunate that despite requests from diplomates and other stakeholders, UCNS has decided to impose new requirements and additional fees on diplomates who have unexpired certificates based on passing an examination that granted a 10-year certification,”

For context, Dr. Rapoport explained what has happened to him and about 200 neurologists and a few other specialists who took the first UCNS certifying exam in Headache Medicine. “I sat for the first exam in a testing center in 2006, after paying a large fee. I passed and was granted a certificate for a 10-year certification in Headache Medicine. Prior to the expiration of that certificate, I was told I had to pay about $1,800 and take a similar examination to certify for another 10 years. I was not sure I needed to do that, but I did so anyway and passed and was granted a new, dated certificate for another 10 years of certification in Headache Medicine. Shortly after that I began to get notices from UCNS saying that they were changing their certification process and I would soon have to read their designated articles, take an examination on that literature, pay $175 for this privilege of C-Cert yearly, all in spite of the fact that I had a valid certificate for 10 years of certification.”

After complaints from Dr. Rapoport and many others, “UCNS said we would only have to do this when we had 5 years left on our certification. When they advertised this new C-Cert plan on the AAN Headache Listserv, even though advertising was against the rules of the Listserv, I complained about it saying we had paid for a 10-year certification. Their response was to abruptly take me off the Listserv. Then they temporarily shut it down when others agreed with what I had written.”

Dr. Rapoport has the certificate that proves that he has 6 years left on his certification, but UCNS will not recognize this, he said. “I believe that to be unfair, unethical, and probably illegal, as do many senior Headache specialists in the country who have the same issue. The attorney for the UCNS, who is also the attorney for the AAN, has disregarded our objections to this move.”

Now the NBPAS will be recertifying Headache Medicine doctors and those of other specialties who are in a similar situation and do not want to pay for the privilege of taking exams yearly when they have already been certified. “I expect many specialists will switch to this new way of certifying,” Dr. Rapoport said.

“I believe the UCNS has cheapened the value of their certifications by not honoring them,” Dr. Rapoort said.

Dr. Mathew reports that he collects no salary for his role with NBPAS, but receives reimbursement for travel expenses, and occasionally receives honoraria for speaking on behalf of NBPAS.

The National Board of Physicians and Surgeons (NBPAS) has announced that they are recertifying United Council of Neurologic Subspecialties (UCNS) diplomates as of Nov. 1, 2020. Recertification will include physicians who were initially board certified with UCNS in the subspecialties of autonomic disorders, behavioral neurology and neuropsychiatry, clinical neuromuscular pathology, geriatric neurology, headache medicine, neurocritical care, neuroimaging, and neuro-oncology.

In 2020, UCNS transitioned to a new continuous-certification (C-cert) model that requires its diplomates to pay an annual fee of $175 and complete a 25-question online quiz based on preselected journal articles with an 80% passing grade. In a press release outlining the details of the new C-cert program, UCNS said that diplomates began the transition last year by “attesting they have participated in subspecialty-specific continuing medical education (CME) requirements from the time their most recent certificate was issued through 2019.” Diplomates have a 2-year window, which began in 2019, to meet these transitional CME requirements and complete an attestation statement before their certification lapses. “Diplomates with a status of ‘meeting requirements’ will be issued a replacement certificate that shows their original certification date and will reflect there is no expiration date after they pay the first annual C-cert fee in 2020,” UCNS said in the press release.

“It is unfortunate that despite requests from diplomates and other stakeholders, UCNS has decided to impose new requirements and additional fees on diplomates who have unexpired certificates based on passing an examination that granted a 10-year certification,” Paul G. Mathew, MD, assistant professor of neurology at Harvard Medical School in Boston and Director of Legislative Affairs at NBPAS, said in an interview. “A one-size-fits-all approach for learning with preselected articles is not ideal, and physicians should be able to choose CME and other learning activities that best suit their individual interests and practice.”

The added requirements and fees have caused some UCNS diplomates to consider letting their certification lapse, Dr. Mathew said, but the NBPAS decision offers them a new path to recertification. “Many physicians who would have otherwise let their certification lapse and would no longer be considered board certified in headache medicine and other UCNS subspecialties will now have the option to recertify with NBPAS,” he said.

NBPAS was formed in 2014 in response to controversial American Board of Medical Specialties Maintenance of Certification (MOC) programs. NBPAS recertifies diplomates of all specialties and subspecialties offered by the ABMS and its member boards, including board certification in neurology and neurologic subspecialties offered by the American Board of Psychiatry and Neurology.

Board recertification with NBPAS requires an unrestricted license to practice medicine in the United States, an initial certification with ABPN, the American Osteopathic Association, and/or UCNS, a medical staff appointment/membership in good standing, active hospital privileges based on specialty, and 50 hours of relevant CME credits every 2 years.

“Although MOC compliance is not required for licensure, the vast majority of insurance carriers in the United States require to some extent that their physicians be MOC compliant. As such, the ABMS has a monopoly in that a physician cannot practice medicine without complying with MOC,” Dr. Mathew said. “That’s very gradually changing.”

So far, 13 states have passed legislation limiting ABMS MOC compliance as a requirement for credentialing or licensure, and 136 healthcare institutions have recognized NBPAS as a pathway for physician credentialing, according to an NBPAS press release.
 

Changing the rules

Alan Rapoport, MD, was asked to comment on the recertification situtaion. Dr. Rapoport is clinical professor of neurology at UCLA and the Editor in Chief of Neurology Reviews. “As Dr. Mathew aptly states, it is unfortunate that despite requests from diplomates and other stakeholders, UCNS has decided to impose new requirements and additional fees on diplomates who have unexpired certificates based on passing an examination that granted a 10-year certification,”

For context, Dr. Rapoport explained what has happened to him and about 200 neurologists and a few other specialists who took the first UCNS certifying exam in Headache Medicine. “I sat for the first exam in a testing center in 2006, after paying a large fee. I passed and was granted a certificate for a 10-year certification in Headache Medicine. Prior to the expiration of that certificate, I was told I had to pay about $1,800 and take a similar examination to certify for another 10 years. I was not sure I needed to do that, but I did so anyway and passed and was granted a new, dated certificate for another 10 years of certification in Headache Medicine. Shortly after that I began to get notices from UCNS saying that they were changing their certification process and I would soon have to read their designated articles, take an examination on that literature, pay $175 for this privilege of C-Cert yearly, all in spite of the fact that I had a valid certificate for 10 years of certification.”

After complaints from Dr. Rapoport and many others, “UCNS said we would only have to do this when we had 5 years left on our certification. When they advertised this new C-Cert plan on the AAN Headache Listserv, even though advertising was against the rules of the Listserv, I complained about it saying we had paid for a 10-year certification. Their response was to abruptly take me off the Listserv. Then they temporarily shut it down when others agreed with what I had written.”

Dr. Rapoport has the certificate that proves that he has 6 years left on his certification, but UCNS will not recognize this, he said. “I believe that to be unfair, unethical, and probably illegal, as do many senior Headache specialists in the country who have the same issue. The attorney for the UCNS, who is also the attorney for the AAN, has disregarded our objections to this move.”

Now the NBPAS will be recertifying Headache Medicine doctors and those of other specialties who are in a similar situation and do not want to pay for the privilege of taking exams yearly when they have already been certified. “I expect many specialists will switch to this new way of certifying,” Dr. Rapoport said.

“I believe the UCNS has cheapened the value of their certifications by not honoring them,” Dr. Rapoort said.

Dr. Mathew reports that he collects no salary for his role with NBPAS, but receives reimbursement for travel expenses, and occasionally receives honoraria for speaking on behalf of NBPAS.

The National Board of Physicians and Surgeons (NBPAS) has announced that they are recertifying United Council of Neurologic Subspecialties (UCNS) diplomates as of Nov. 1, 2020. Recertification will include physicians who were initially board certified with UCNS in the subspecialties of autonomic disorders, behavioral neurology and neuropsychiatry, clinical neuromuscular pathology, geriatric neurology, headache medicine, neurocritical care, neuroimaging, and neuro-oncology.

In 2020, UCNS transitioned to a new continuous-certification (C-cert) model that requires its diplomates to pay an annual fee of $175 and complete a 25-question online quiz based on preselected journal articles with an 80% passing grade. In a press release outlining the details of the new C-cert program, UCNS said that diplomates began the transition last year by “attesting they have participated in subspecialty-specific continuing medical education (CME) requirements from the time their most recent certificate was issued through 2019.” Diplomates have a 2-year window, which began in 2019, to meet these transitional CME requirements and complete an attestation statement before their certification lapses. “Diplomates with a status of ‘meeting requirements’ will be issued a replacement certificate that shows their original certification date and will reflect there is no expiration date after they pay the first annual C-cert fee in 2020,” UCNS said in the press release.

“It is unfortunate that despite requests from diplomates and other stakeholders, UCNS has decided to impose new requirements and additional fees on diplomates who have unexpired certificates based on passing an examination that granted a 10-year certification,” Paul G. Mathew, MD, assistant professor of neurology at Harvard Medical School in Boston and Director of Legislative Affairs at NBPAS, said in an interview. “A one-size-fits-all approach for learning with preselected articles is not ideal, and physicians should be able to choose CME and other learning activities that best suit their individual interests and practice.”

The added requirements and fees have caused some UCNS diplomates to consider letting their certification lapse, Dr. Mathew said, but the NBPAS decision offers them a new path to recertification. “Many physicians who would have otherwise let their certification lapse and would no longer be considered board certified in headache medicine and other UCNS subspecialties will now have the option to recertify with NBPAS,” he said.

NBPAS was formed in 2014 in response to controversial American Board of Medical Specialties Maintenance of Certification (MOC) programs. NBPAS recertifies diplomates of all specialties and subspecialties offered by the ABMS and its member boards, including board certification in neurology and neurologic subspecialties offered by the American Board of Psychiatry and Neurology.

Board recertification with NBPAS requires an unrestricted license to practice medicine in the United States, an initial certification with ABPN, the American Osteopathic Association, and/or UCNS, a medical staff appointment/membership in good standing, active hospital privileges based on specialty, and 50 hours of relevant CME credits every 2 years.

“Although MOC compliance is not required for licensure, the vast majority of insurance carriers in the United States require to some extent that their physicians be MOC compliant. As such, the ABMS has a monopoly in that a physician cannot practice medicine without complying with MOC,” Dr. Mathew said. “That’s very gradually changing.”

So far, 13 states have passed legislation limiting ABMS MOC compliance as a requirement for credentialing or licensure, and 136 healthcare institutions have recognized NBPAS as a pathway for physician credentialing, according to an NBPAS press release.
 

Changing the rules

Alan Rapoport, MD, was asked to comment on the recertification situtaion. Dr. Rapoport is clinical professor of neurology at UCLA and the Editor in Chief of Neurology Reviews. “As Dr. Mathew aptly states, it is unfortunate that despite requests from diplomates and other stakeholders, UCNS has decided to impose new requirements and additional fees on diplomates who have unexpired certificates based on passing an examination that granted a 10-year certification,”

For context, Dr. Rapoport explained what has happened to him and about 200 neurologists and a few other specialists who took the first UCNS certifying exam in Headache Medicine. “I sat for the first exam in a testing center in 2006, after paying a large fee. I passed and was granted a certificate for a 10-year certification in Headache Medicine. Prior to the expiration of that certificate, I was told I had to pay about $1,800 and take a similar examination to certify for another 10 years. I was not sure I needed to do that, but I did so anyway and passed and was granted a new, dated certificate for another 10 years of certification in Headache Medicine. Shortly after that I began to get notices from UCNS saying that they were changing their certification process and I would soon have to read their designated articles, take an examination on that literature, pay $175 for this privilege of C-Cert yearly, all in spite of the fact that I had a valid certificate for 10 years of certification.”

After complaints from Dr. Rapoport and many others, “UCNS said we would only have to do this when we had 5 years left on our certification. When they advertised this new C-Cert plan on the AAN Headache Listserv, even though advertising was against the rules of the Listserv, I complained about it saying we had paid for a 10-year certification. Their response was to abruptly take me off the Listserv. Then they temporarily shut it down when others agreed with what I had written.”

Dr. Rapoport has the certificate that proves that he has 6 years left on his certification, but UCNS will not recognize this, he said. “I believe that to be unfair, unethical, and probably illegal, as do many senior Headache specialists in the country who have the same issue. The attorney for the UCNS, who is also the attorney for the AAN, has disregarded our objections to this move.”

Now the NBPAS will be recertifying Headache Medicine doctors and those of other specialties who are in a similar situation and do not want to pay for the privilege of taking exams yearly when they have already been certified. “I expect many specialists will switch to this new way of certifying,” Dr. Rapoport said.

“I believe the UCNS has cheapened the value of their certifications by not honoring them,” Dr. Rapoort said.

Dr. Mathew reports that he collects no salary for his role with NBPAS, but receives reimbursement for travel expenses, and occasionally receives honoraria for speaking on behalf of NBPAS.

Background: Higher glucose immediately following acute ischemic stroke is known to be associated with poor outcomes. Patients with elevated glucoses in the aftermath of an acute ischemic stroke are more likely to have expansion of ischemic area and are more likely to have hemorrhagic conversion.

Dr. Fritz is assistant professor of medicine and the director of hospitalist operations at St. Louis University School of Medicine.

Background: Higher glucose immediately following acute ischemic stroke is known to be associated with poor outcomes. Patients with elevated glucoses in the aftermath of an acute ischemic stroke are more likely to have expansion of ischemic area and are more likely to have hemorrhagic conversion.

Dr. Fritz is assistant professor of medicine and the director of hospitalist operations at St. Louis University School of Medicine.

Background: Higher glucose immediately following acute ischemic stroke is known to be associated with poor outcomes. Patients with elevated glucoses in the aftermath of an acute ischemic stroke are more likely to have expansion of ischemic area and are more likely to have hemorrhagic conversion.

Dr. Fritz is assistant professor of medicine and the director of hospitalist operations at St. Louis University School of Medicine.

An eye exam may be all that is needed to diagnose Parkinson’s disease, new research shows. Using an advanced machine-learning algorithm and fundus eye images, which depict the small blood vessels and more at the back of the eye, investigators are able to classify patients with Parkinson’s disease compared against a control group. “We discovered that micro blood vessels decreased in both size and number in patients with Parkinson’s disease,” said Maximillian Diaz, a PhD student at the University of Florida, Gainesville.

The simple eye examination may offer a way to diagnose Parkinson’s early in the disease progression.

Mr. Diaz said the test could be incorporated to a patient’s annual physical examination not only to look for Parkinson’s disease but also for other neurological diseases. Researchers at the University of Florida are also looking at whether the same technique can diagnose Alzheimer’s disease.

The beauty of this is that “the technique is simple,” he said. “What surprised us is that we can do this with fundus images, which can be taken in a clinical setting with a lens that attaches to your smartphone. It’s affordable and portable and it takes less than a minute.”
 

Machine learning on fundus eye images

Researchers, under the direction of Ruogu Fang, PhD, director of the J. Crayton Pruitt Department of Biomedical Engineering’s Smart Medical Informatics Learning and Evaluation Lab (SMILE) at the University of Florida, Gainesville, collected fundus eye images from 476 age- and gender-matched individuals, 238 diagnosed with Parkinson’s disease and 238 control group images. Another set of 100 images were collected from the University of Florida database using green color channels (UKB-Green and UF-UKB Green) and used to improve vessel segmentation. Of these, 28 were controls and 72 from patients with Parkinson’s disease. Researchers added 44 more control images from the U.K. Biobank to complete the second age- and gender-matched dataset.

“We used 80% of the images to develop the machine-learning network,” Mr. Diaz said. The other 20% of images, which were new to the algorithm, were used to test it, to determine true or false, Parkinson’s disease or control?

“We were able to achieve an accuracy of 85%,” Mr. Diaz said. Currently, there are no biomarkers to diagnose Parkinson’s disease. The disease is only recognizable once 80% of dopaminergic cells have already decayed. “Clinically, there’s no way to tell how long someone has had it,” Mr. Diaz said. He hopes that by doing additional research and testing earlier – with a longitudinal study of images – a pattern may be detected to better predict disease.
 

Eye vasculature reveals disease

“This concept [studying eye vasculature] is getting a lot of interest right now,” said Anant Madabhushi, PhD, Case Western Reserve University, Cleveland. “The eye is the proverbial window to the soul, and in this case, shows what’s happening in rest of the body.”

Dr. Madabhushi, who was not involved in the Parkinson’s research, has also been working with a team in Cleveland to look at how vessels in the eye predict response to drug therapies in diabetic macular edema, including treatment durability. “What we’ve found is the more twisted the vessels, the more constricted, and the less likely the person would respond to therapy,” he said, adding that studying the pathology of the eye makes a lot of sense. “The arrangement of vessels in the eye are likely to have implications in all kinds of diseases.”

Since Parkinson’s disease does not have any biomarkers, this technology could be very useful in diagnosis. “With specific quantitative measurements, we could have computational imaging biomarkers to predict the risk of onset of Parkinson’s, and the prognosis of disease. That’s the true utility of this approach,” he said.

Mr. Diaz disclosed no relevant financial relationships. Dr. Madabhushi has consulted for Aiforia and has had research sponsored by AstraZeneca, Bristol-Myers Squibb, and Boehringer Ingelheim.

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

An eye exam may be all that is needed to diagnose Parkinson’s disease, new research shows. Using an advanced machine-learning algorithm and fundus eye images, which depict the small blood vessels and more at the back of the eye, investigators are able to classify patients with Parkinson’s disease compared against a control group. “We discovered that micro blood vessels decreased in both size and number in patients with Parkinson’s disease,” said Maximillian Diaz, a PhD student at the University of Florida, Gainesville.

The simple eye examination may offer a way to diagnose Parkinson’s early in the disease progression.

Mr. Diaz said the test could be incorporated to a patient’s annual physical examination not only to look for Parkinson’s disease but also for other neurological diseases. Researchers at the University of Florida are also looking at whether the same technique can diagnose Alzheimer’s disease.

The beauty of this is that “the technique is simple,” he said. “What surprised us is that we can do this with fundus images, which can be taken in a clinical setting with a lens that attaches to your smartphone. It’s affordable and portable and it takes less than a minute.”
 

Machine learning on fundus eye images

Researchers, under the direction of Ruogu Fang, PhD, director of the J. Crayton Pruitt Department of Biomedical Engineering’s Smart Medical Informatics Learning and Evaluation Lab (SMILE) at the University of Florida, Gainesville, collected fundus eye images from 476 age- and gender-matched individuals, 238 diagnosed with Parkinson’s disease and 238 control group images. Another set of 100 images were collected from the University of Florida database using green color channels (UKB-Green and UF-UKB Green) and used to improve vessel segmentation. Of these, 28 were controls and 72 from patients with Parkinson’s disease. Researchers added 44 more control images from the U.K. Biobank to complete the second age- and gender-matched dataset.

“We used 80% of the images to develop the machine-learning network,” Mr. Diaz said. The other 20% of images, which were new to the algorithm, were used to test it, to determine true or false, Parkinson’s disease or control?

“We were able to achieve an accuracy of 85%,” Mr. Diaz said. Currently, there are no biomarkers to diagnose Parkinson’s disease. The disease is only recognizable once 80% of dopaminergic cells have already decayed. “Clinically, there’s no way to tell how long someone has had it,” Mr. Diaz said. He hopes that by doing additional research and testing earlier – with a longitudinal study of images – a pattern may be detected to better predict disease.
 

Eye vasculature reveals disease

“This concept [studying eye vasculature] is getting a lot of interest right now,” said Anant Madabhushi, PhD, Case Western Reserve University, Cleveland. “The eye is the proverbial window to the soul, and in this case, shows what’s happening in rest of the body.”

Dr. Madabhushi, who was not involved in the Parkinson’s research, has also been working with a team in Cleveland to look at how vessels in the eye predict response to drug therapies in diabetic macular edema, including treatment durability. “What we’ve found is the more twisted the vessels, the more constricted, and the less likely the person would respond to therapy,” he said, adding that studying the pathology of the eye makes a lot of sense. “The arrangement of vessels in the eye are likely to have implications in all kinds of diseases.”

Since Parkinson’s disease does not have any biomarkers, this technology could be very useful in diagnosis. “With specific quantitative measurements, we could have computational imaging biomarkers to predict the risk of onset of Parkinson’s, and the prognosis of disease. That’s the true utility of this approach,” he said.

Mr. Diaz disclosed no relevant financial relationships. Dr. Madabhushi has consulted for Aiforia and has had research sponsored by AstraZeneca, Bristol-Myers Squibb, and Boehringer Ingelheim.

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

An eye exam may be all that is needed to diagnose Parkinson’s disease, new research shows. Using an advanced machine-learning algorithm and fundus eye images, which depict the small blood vessels and more at the back of the eye, investigators are able to classify patients with Parkinson’s disease compared against a control group. “We discovered that micro blood vessels decreased in both size and number in patients with Parkinson’s disease,” said Maximillian Diaz, a PhD student at the University of Florida, Gainesville.

The simple eye examination may offer a way to diagnose Parkinson’s early in the disease progression.

Mr. Diaz said the test could be incorporated to a patient’s annual physical examination not only to look for Parkinson’s disease but also for other neurological diseases. Researchers at the University of Florida are also looking at whether the same technique can diagnose Alzheimer’s disease.

The beauty of this is that “the technique is simple,” he said. “What surprised us is that we can do this with fundus images, which can be taken in a clinical setting with a lens that attaches to your smartphone. It’s affordable and portable and it takes less than a minute.”
 

Machine learning on fundus eye images

Researchers, under the direction of Ruogu Fang, PhD, director of the J. Crayton Pruitt Department of Biomedical Engineering’s Smart Medical Informatics Learning and Evaluation Lab (SMILE) at the University of Florida, Gainesville, collected fundus eye images from 476 age- and gender-matched individuals, 238 diagnosed with Parkinson’s disease and 238 control group images. Another set of 100 images were collected from the University of Florida database using green color channels (UKB-Green and UF-UKB Green) and used to improve vessel segmentation. Of these, 28 were controls and 72 from patients with Parkinson’s disease. Researchers added 44 more control images from the U.K. Biobank to complete the second age- and gender-matched dataset.

“We used 80% of the images to develop the machine-learning network,” Mr. Diaz said. The other 20% of images, which were new to the algorithm, were used to test it, to determine true or false, Parkinson’s disease or control?

“We were able to achieve an accuracy of 85%,” Mr. Diaz said. Currently, there are no biomarkers to diagnose Parkinson’s disease. The disease is only recognizable once 80% of dopaminergic cells have already decayed. “Clinically, there’s no way to tell how long someone has had it,” Mr. Diaz said. He hopes that by doing additional research and testing earlier – with a longitudinal study of images – a pattern may be detected to better predict disease.
 

Eye vasculature reveals disease

“This concept [studying eye vasculature] is getting a lot of interest right now,” said Anant Madabhushi, PhD, Case Western Reserve University, Cleveland. “The eye is the proverbial window to the soul, and in this case, shows what’s happening in rest of the body.”

Dr. Madabhushi, who was not involved in the Parkinson’s research, has also been working with a team in Cleveland to look at how vessels in the eye predict response to drug therapies in diabetic macular edema, including treatment durability. “What we’ve found is the more twisted the vessels, the more constricted, and the less likely the person would respond to therapy,” he said, adding that studying the pathology of the eye makes a lot of sense. “The arrangement of vessels in the eye are likely to have implications in all kinds of diseases.”

Since Parkinson’s disease does not have any biomarkers, this technology could be very useful in diagnosis. “With specific quantitative measurements, we could have computational imaging biomarkers to predict the risk of onset of Parkinson’s, and the prognosis of disease. That’s the true utility of this approach,” he said.

Mr. Diaz disclosed no relevant financial relationships. Dr. Madabhushi has consulted for Aiforia and has had research sponsored by AstraZeneca, Bristol-Myers Squibb, and Boehringer Ingelheim.

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

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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