Pauline Anderson

Sensitivity to specific common odors correlates with symptoms of depression or anxiety, new research shows.

A study of more than 400 participants showed that symptoms of anxiety were associated with heightened awareness of floral scents or kitchen smells, while depression was linked to increased awareness of social odors including “good” and “bad” smells of other people.

“The assessment of meta-cognitive abilities may be a useful tool in assessing depressive, anxiety, and social anxiety symptoms,” study investigator Cinzia Cecchetto, PhD student, postdoctoral researcher, department of general psychology, University of Padua, Italy, told this news organization.

The findings were published online in the Journal of Affective Disorders.
 

Smell perception

Previous studies have shown a strong relationship between reduced odor detection and symptoms of depression, with less clear evidence of a link between olfactory perception and symptoms of anxiety, Dr. Cecchetto said.

However, few studies have investigated to what extent individuals with symptoms of anxiety or depression are aware of, or pay attention to, odors in their environment, she added.

The study included 429 healthy participants (76.9% women, aged 18-45 years) recruited through social media. The age cut-off was 45 because evidence shows that olfactory perceptions start to decline at that time of life, Dr. Cecchetto noted.

Participants completed psychological questionnaires, including the Beck Depression Inventory-II, the Beck Anxiety Inventory, and the Liebowitz Social Anxiety Scale.

They also completed olfactory questionnaires, including the Odor Awareness Scale for evaluating the degree to which an individual focuses on olfactory stimuli such as that from food; the Affective Impact of Odor scale for assessing how odors affect liking and memory for people, places, and things; the Vividness of Olfactory Imagery Questionnaire, which examines ability to form olfactory images such as fragrances from a garden; and the Social Odor Scale, which assesses awareness of social odors such as sweat in everyday interactions.

Results showed that general anxiety symptoms were a significant predictor of higher levels of awareness of common odors.

The investigators note that this finding is similar to that from previous research in which patients with panic disorder reported higher olfactory sensitivity, reactivity, and awareness of odors compared with a control group. It is also in line with clinical features of anxiety, in which individuals maintain heightened vigilance, hyperarousal, and action readiness to respond to sudden danger.

Individuals with social anxiety symptoms reported being less attentive toward social odors.

This finding is at odds with the tendency of individuals with social anxiety to continuously monitor the environment for signs of potential negative evaluations by others.

In addition, it contradicts findings from previous studies showing that social anxiety is associated with enhanced startle reactivity and faster processing of social odor anxiety signals, compared with healthy controls, the investigators note.
 

Clinical implications?

“A possible explanation for these conflicting findings could be that in our study we didn’t present real odors to participants, but asked them if they usually pay attention to these odors,” lead author Elisa Dal Bò, PhD student, Padova Neuroscience Center and department of general psychology, University of Padua, told this news organization.

“Indeed, other studies have shown individuals with social anxiety focus their attention more on themselves and avoid paying attention to other people during social interactions,” she added.

Depressive symptoms were a significant predictor of higher social odor awareness and lower affective responses to odors. Some past studies showed that “depression is characterized by an increased attention to social stimuli induced by the fear of social rejection,” Ms. Dal Bò noted.

The current findings showing that depression symptoms were associated with higher social odor awareness while social anxiety symptoms were associated with lower social odor awareness are at odds with what was hypothesized, Dr. Cecchetto said.

“Actually we were expecting the opposite pattern, and that’s why it’s important to investigate more deeply these meta-cognitive abilities,” she said.

Neither depressive nor anxiety symptoms were significant predictors of olfactory imagery.

Female respondents were more attentive to, and aware of, odors than men. This finding is “quite common in the literature,” Dr. Cecchetto noted.

Although preliminary, the results could eventually have clinical implications, the investigators note. Olfactory metacognitive abilities, obtained through questionnaires, could be used to assess potential olfactory impairment, which could signal future risk for psychiatric symptoms.

However, the relatively young age of participants in the study and the prevalence of women limits the generalization of the findings, the researchers note. In addition, clinical symptoms were self-reported and were not verified by health care professionals.
 

‘Not enough evidence’

Commenting for this news organization, Philip R. Muskin, MD, professor of clinical psychiatry, Columbia University Medical Center, New York, said he did not find the results surprising.

For example, that individuals with social anxiety are not particularly aware of others’ smell “makes perfect sense” because “people with social anxiety disorder are concerned with themselves,” he said.

Dr. Muskin, who has an interest in and has written about olfactory function, was not involved with the research.

He noted several study limitations. First, participants just reported on their smell awareness, but “having people actually smell stuff might have been more interesting.”

In addition, the study population was relatively young, mostly women, and women’s olfactory sensitivity changes throughout the menstrual cycle, Dr. Muskin said.

“We don’t know where these women are in their cycles when they’re reporting their awareness of odors,” he said. “It would be good to know if the women were all in the luteal phase or were premenstrual because that might correlate with their anxiety or depressive symptoms.”

Asking a patient about smell awareness may provide some insight when assessing for symptoms of depression, along with obtaining details on such things as sleep, Dr. Muskin noted.

However, he does not think the new findings are enough to include olfactory awareness in the interview process. “It’s not enough evidence to use as a clinical tool for diagnosis, and I don’t see this is clinically useful yet.”

The study was supported by the European Commission Horizon 2020 research and innovation program and the Austrian Science Fund. The investigators and Dr. Muskin have reported no relevant financial relationships.

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

Sensitivity to specific common odors correlates with symptoms of depression or anxiety, new research shows.

A study of more than 400 participants showed that symptoms of anxiety were associated with heightened awareness of floral scents or kitchen smells, while depression was linked to increased awareness of social odors including “good” and “bad” smells of other people.

“The assessment of meta-cognitive abilities may be a useful tool in assessing depressive, anxiety, and social anxiety symptoms,” study investigator Cinzia Cecchetto, PhD student, postdoctoral researcher, department of general psychology, University of Padua, Italy, told this news organization.

The findings were published online in the Journal of Affective Disorders.
 

Smell perception

Previous studies have shown a strong relationship between reduced odor detection and symptoms of depression, with less clear evidence of a link between olfactory perception and symptoms of anxiety, Dr. Cecchetto said.

However, few studies have investigated to what extent individuals with symptoms of anxiety or depression are aware of, or pay attention to, odors in their environment, she added.

The study included 429 healthy participants (76.9% women, aged 18-45 years) recruited through social media. The age cut-off was 45 because evidence shows that olfactory perceptions start to decline at that time of life, Dr. Cecchetto noted.

Participants completed psychological questionnaires, including the Beck Depression Inventory-II, the Beck Anxiety Inventory, and the Liebowitz Social Anxiety Scale.

They also completed olfactory questionnaires, including the Odor Awareness Scale for evaluating the degree to which an individual focuses on olfactory stimuli such as that from food; the Affective Impact of Odor scale for assessing how odors affect liking and memory for people, places, and things; the Vividness of Olfactory Imagery Questionnaire, which examines ability to form olfactory images such as fragrances from a garden; and the Social Odor Scale, which assesses awareness of social odors such as sweat in everyday interactions.

Results showed that general anxiety symptoms were a significant predictor of higher levels of awareness of common odors.

The investigators note that this finding is similar to that from previous research in which patients with panic disorder reported higher olfactory sensitivity, reactivity, and awareness of odors compared with a control group. It is also in line with clinical features of anxiety, in which individuals maintain heightened vigilance, hyperarousal, and action readiness to respond to sudden danger.

Individuals with social anxiety symptoms reported being less attentive toward social odors.

This finding is at odds with the tendency of individuals with social anxiety to continuously monitor the environment for signs of potential negative evaluations by others.

In addition, it contradicts findings from previous studies showing that social anxiety is associated with enhanced startle reactivity and faster processing of social odor anxiety signals, compared with healthy controls, the investigators note.
 

Clinical implications?

“A possible explanation for these conflicting findings could be that in our study we didn’t present real odors to participants, but asked them if they usually pay attention to these odors,” lead author Elisa Dal Bò, PhD student, Padova Neuroscience Center and department of general psychology, University of Padua, told this news organization.

“Indeed, other studies have shown individuals with social anxiety focus their attention more on themselves and avoid paying attention to other people during social interactions,” she added.

Depressive symptoms were a significant predictor of higher social odor awareness and lower affective responses to odors. Some past studies showed that “depression is characterized by an increased attention to social stimuli induced by the fear of social rejection,” Ms. Dal Bò noted.

The current findings showing that depression symptoms were associated with higher social odor awareness while social anxiety symptoms were associated with lower social odor awareness are at odds with what was hypothesized, Dr. Cecchetto said.

“Actually we were expecting the opposite pattern, and that’s why it’s important to investigate more deeply these meta-cognitive abilities,” she said.

Neither depressive nor anxiety symptoms were significant predictors of olfactory imagery.

Female respondents were more attentive to, and aware of, odors than men. This finding is “quite common in the literature,” Dr. Cecchetto noted.

Although preliminary, the results could eventually have clinical implications, the investigators note. Olfactory metacognitive abilities, obtained through questionnaires, could be used to assess potential olfactory impairment, which could signal future risk for psychiatric symptoms.

However, the relatively young age of participants in the study and the prevalence of women limits the generalization of the findings, the researchers note. In addition, clinical symptoms were self-reported and were not verified by health care professionals.
 

‘Not enough evidence’

Commenting for this news organization, Philip R. Muskin, MD, professor of clinical psychiatry, Columbia University Medical Center, New York, said he did not find the results surprising.

For example, that individuals with social anxiety are not particularly aware of others’ smell “makes perfect sense” because “people with social anxiety disorder are concerned with themselves,” he said.

Dr. Muskin, who has an interest in and has written about olfactory function, was not involved with the research.

He noted several study limitations. First, participants just reported on their smell awareness, but “having people actually smell stuff might have been more interesting.”

In addition, the study population was relatively young, mostly women, and women’s olfactory sensitivity changes throughout the menstrual cycle, Dr. Muskin said.

“We don’t know where these women are in their cycles when they’re reporting their awareness of odors,” he said. “It would be good to know if the women were all in the luteal phase or were premenstrual because that might correlate with their anxiety or depressive symptoms.”

Asking a patient about smell awareness may provide some insight when assessing for symptoms of depression, along with obtaining details on such things as sleep, Dr. Muskin noted.

However, he does not think the new findings are enough to include olfactory awareness in the interview process. “It’s not enough evidence to use as a clinical tool for diagnosis, and I don’t see this is clinically useful yet.”

The study was supported by the European Commission Horizon 2020 research and innovation program and the Austrian Science Fund. The investigators and Dr. Muskin have reported no relevant financial relationships.

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

Sensitivity to specific common odors correlates with symptoms of depression or anxiety, new research shows.

A study of more than 400 participants showed that symptoms of anxiety were associated with heightened awareness of floral scents or kitchen smells, while depression was linked to increased awareness of social odors including “good” and “bad” smells of other people.

“The assessment of meta-cognitive abilities may be a useful tool in assessing depressive, anxiety, and social anxiety symptoms,” study investigator Cinzia Cecchetto, PhD student, postdoctoral researcher, department of general psychology, University of Padua, Italy, told this news organization.

The findings were published online in the Journal of Affective Disorders.
 

Smell perception

Previous studies have shown a strong relationship between reduced odor detection and symptoms of depression, with less clear evidence of a link between olfactory perception and symptoms of anxiety, Dr. Cecchetto said.

However, few studies have investigated to what extent individuals with symptoms of anxiety or depression are aware of, or pay attention to, odors in their environment, she added.

The study included 429 healthy participants (76.9% women, aged 18-45 years) recruited through social media. The age cut-off was 45 because evidence shows that olfactory perceptions start to decline at that time of life, Dr. Cecchetto noted.

Participants completed psychological questionnaires, including the Beck Depression Inventory-II, the Beck Anxiety Inventory, and the Liebowitz Social Anxiety Scale.

They also completed olfactory questionnaires, including the Odor Awareness Scale for evaluating the degree to which an individual focuses on olfactory stimuli such as that from food; the Affective Impact of Odor scale for assessing how odors affect liking and memory for people, places, and things; the Vividness of Olfactory Imagery Questionnaire, which examines ability to form olfactory images such as fragrances from a garden; and the Social Odor Scale, which assesses awareness of social odors such as sweat in everyday interactions.

Results showed that general anxiety symptoms were a significant predictor of higher levels of awareness of common odors.

The investigators note that this finding is similar to that from previous research in which patients with panic disorder reported higher olfactory sensitivity, reactivity, and awareness of odors compared with a control group. It is also in line with clinical features of anxiety, in which individuals maintain heightened vigilance, hyperarousal, and action readiness to respond to sudden danger.

Individuals with social anxiety symptoms reported being less attentive toward social odors.

This finding is at odds with the tendency of individuals with social anxiety to continuously monitor the environment for signs of potential negative evaluations by others.

In addition, it contradicts findings from previous studies showing that social anxiety is associated with enhanced startle reactivity and faster processing of social odor anxiety signals, compared with healthy controls, the investigators note.
 

Clinical implications?

“A possible explanation for these conflicting findings could be that in our study we didn’t present real odors to participants, but asked them if they usually pay attention to these odors,” lead author Elisa Dal Bò, PhD student, Padova Neuroscience Center and department of general psychology, University of Padua, told this news organization.

“Indeed, other studies have shown individuals with social anxiety focus their attention more on themselves and avoid paying attention to other people during social interactions,” she added.

Depressive symptoms were a significant predictor of higher social odor awareness and lower affective responses to odors. Some past studies showed that “depression is characterized by an increased attention to social stimuli induced by the fear of social rejection,” Ms. Dal Bò noted.

The current findings showing that depression symptoms were associated with higher social odor awareness while social anxiety symptoms were associated with lower social odor awareness are at odds with what was hypothesized, Dr. Cecchetto said.

“Actually we were expecting the opposite pattern, and that’s why it’s important to investigate more deeply these meta-cognitive abilities,” she said.

Neither depressive nor anxiety symptoms were significant predictors of olfactory imagery.

Female respondents were more attentive to, and aware of, odors than men. This finding is “quite common in the literature,” Dr. Cecchetto noted.

Although preliminary, the results could eventually have clinical implications, the investigators note. Olfactory metacognitive abilities, obtained through questionnaires, could be used to assess potential olfactory impairment, which could signal future risk for psychiatric symptoms.

However, the relatively young age of participants in the study and the prevalence of women limits the generalization of the findings, the researchers note. In addition, clinical symptoms were self-reported and were not verified by health care professionals.
 

‘Not enough evidence’

Commenting for this news organization, Philip R. Muskin, MD, professor of clinical psychiatry, Columbia University Medical Center, New York, said he did not find the results surprising.

For example, that individuals with social anxiety are not particularly aware of others’ smell “makes perfect sense” because “people with social anxiety disorder are concerned with themselves,” he said.

Dr. Muskin, who has an interest in and has written about olfactory function, was not involved with the research.

He noted several study limitations. First, participants just reported on their smell awareness, but “having people actually smell stuff might have been more interesting.”

In addition, the study population was relatively young, mostly women, and women’s olfactory sensitivity changes throughout the menstrual cycle, Dr. Muskin said.

“We don’t know where these women are in their cycles when they’re reporting their awareness of odors,” he said. “It would be good to know if the women were all in the luteal phase or were premenstrual because that might correlate with their anxiety or depressive symptoms.”

Asking a patient about smell awareness may provide some insight when assessing for symptoms of depression, along with obtaining details on such things as sleep, Dr. Muskin noted.

However, he does not think the new findings are enough to include olfactory awareness in the interview process. “It’s not enough evidence to use as a clinical tool for diagnosis, and I don’t see this is clinically useful yet.”

The study was supported by the European Commission Horizon 2020 research and innovation program and the Austrian Science Fund. The investigators and Dr. Muskin have reported no relevant financial relationships.

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

An at-home investigational device is a promising noninvasive therapeutic approach for anxiety disorders, results from an open-label pilot trial suggest.

The small study showed users of the Mechanical Affective Touch Therapy (MATT) had improved anxiety and depression symptoms, which corresponded to positive changes in alpha and theta oscillatory activity.

Butler Hospital

Robust safety profile

Therapeutic noninvasive peripheral nerve stimulation is under investigation for anxiety as well as pain and depression. Nerve activation is achieved by delivering electrical or mechanical energy, although most devices to date have used electrical stimulation.

Although electrical stimulation is considered low risk, mechanical stimulation that activates somatosensory pathways has an even more robust safety profile, the investigators note.

The MATT device targets C-tactile fibers (CT) specialized unmyelinated Group C peripheral nerve fibers that fire when stroked at velocities perceived as pleasurable or comforting.

To use the device, participants wear a headset with a small vibrating piece that sits on the mastoid bone behind each ear. These pieces deliver gentle vibrations that can be adjusted by patients.  

During development of the MATT stimulation, researchers noted that an isochronic 10 Hz wave, cycling 2 seconds on and 2 seconds off, induced a state of relaxation and increased occipital alpha oscillations in pilot study participants.

The current study was designed to confirm preliminary efficacy and feasibility signals. The sample included 22 patients (mean age 37.3 years, 72.7% female, 77.3% White). All study participants were diagnosed with an anxiety disorder and had at least moderately severe anxiety symptoms. Some also had symptoms of panic or depression.

Many participants were on medications that weren’t effective, and they wanted to find a nondrug method of relieving their symptoms, said Dr. Carpenter.
 

What’s the mechanism?

Participants learned how to administer the stimulation and adjust the intensity of vibrations to a level where it was consistently detectable but not uncomfortable. Then they received a MATT device to use at home at least twice daily for 20 minutes.

Patients kept daily diaries documenting device use, adverse effects, and technological problems. In-person assessments were held at 2 and 4 weeks.

Researchers collected resting EEG immediately before, and after, the second stimulation session and again following 4 weeks of MATT use.

At baseline and after 2 and 4 weeks, patients self-reported anxiety using the 7-item Generalized Anxiety Disorder (GAD-7) scale, depression with the Beck Depression Inventory (BDI), and stress using the Perceived Stress Scale (PSS). They also reported symptoms with the Depression, Anxiety, Stress Scale (DASS).

Researchers also investigated “interoceptive awareness” or being mindful of your body and internal feelings. For this, they had participants complete the 32-item Multidimensional Assessment of Interoceptive Awareness pre- and post treatment.

Interoceptive awareness “is a whole new area of interest in neuroscience and brain health,” said Dr. Carpenter. “The hypothesis was that one way this device might work is that vibrations would travel to the insular cortex, the part of the brain that involves mindfulness and self-awareness.”
 

Symptom reduction

In the completer sample of 17 participants, mean scores on anxiety and depression symptoms fell significantly from baseline to 4 weeks (all P < .01). For example, the GAD-7 mean score fell from 14.3 to 7.1 and the BDI mean score from 30.6 to 14.8.

The study also showed that mindfulness was enhanced. The MAIA total score increased from 83.1 to 93.5 (P = .014).

Device users had increased alpha and theta brainwave activity, findings that “go along with the concept of decreased anxiety,” said Dr. Carpenter. She noted a recent study of the same patient population showed the device enhanced functional brain connectivity.

This current study was too small to pick up signals showing the device was effective in any particular subpopulation, said Dr. Carpenter.

Unlike other stimulation interventions that require clinic visits, patients use the MATT in the comfort of their own home and at their own convenience.

However, there are still questions surrounding the use of the noninvasive device. For example, said Dr. Carpenter, it’s unclear if it would be more effective if combined with psychotherapy or whether patients can use it while sleeping and driving. A next step could be a sham-controlled trial, she said.

The study was supported by Affect Neuro, developer of MATT therapy, and the National Institute of General Medical Sciences. Dr. Carpenter reports receiving a consultancy fee from Affect Neuro.

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

An at-home investigational device is a promising noninvasive therapeutic approach for anxiety disorders, results from an open-label pilot trial suggest.

The small study showed users of the Mechanical Affective Touch Therapy (MATT) had improved anxiety and depression symptoms, which corresponded to positive changes in alpha and theta oscillatory activity.

Butler Hospital

Robust safety profile

Therapeutic noninvasive peripheral nerve stimulation is under investigation for anxiety as well as pain and depression. Nerve activation is achieved by delivering electrical or mechanical energy, although most devices to date have used electrical stimulation.

Although electrical stimulation is considered low risk, mechanical stimulation that activates somatosensory pathways has an even more robust safety profile, the investigators note.

The MATT device targets C-tactile fibers (CT) specialized unmyelinated Group C peripheral nerve fibers that fire when stroked at velocities perceived as pleasurable or comforting.

To use the device, participants wear a headset with a small vibrating piece that sits on the mastoid bone behind each ear. These pieces deliver gentle vibrations that can be adjusted by patients.  

During development of the MATT stimulation, researchers noted that an isochronic 10 Hz wave, cycling 2 seconds on and 2 seconds off, induced a state of relaxation and increased occipital alpha oscillations in pilot study participants.

The current study was designed to confirm preliminary efficacy and feasibility signals. The sample included 22 patients (mean age 37.3 years, 72.7% female, 77.3% White). All study participants were diagnosed with an anxiety disorder and had at least moderately severe anxiety symptoms. Some also had symptoms of panic or depression.

Many participants were on medications that weren’t effective, and they wanted to find a nondrug method of relieving their symptoms, said Dr. Carpenter.
 

What’s the mechanism?

Participants learned how to administer the stimulation and adjust the intensity of vibrations to a level where it was consistently detectable but not uncomfortable. Then they received a MATT device to use at home at least twice daily for 20 minutes.

Patients kept daily diaries documenting device use, adverse effects, and technological problems. In-person assessments were held at 2 and 4 weeks.

Researchers collected resting EEG immediately before, and after, the second stimulation session and again following 4 weeks of MATT use.

At baseline and after 2 and 4 weeks, patients self-reported anxiety using the 7-item Generalized Anxiety Disorder (GAD-7) scale, depression with the Beck Depression Inventory (BDI), and stress using the Perceived Stress Scale (PSS). They also reported symptoms with the Depression, Anxiety, Stress Scale (DASS).

Researchers also investigated “interoceptive awareness” or being mindful of your body and internal feelings. For this, they had participants complete the 32-item Multidimensional Assessment of Interoceptive Awareness pre- and post treatment.

Interoceptive awareness “is a whole new area of interest in neuroscience and brain health,” said Dr. Carpenter. “The hypothesis was that one way this device might work is that vibrations would travel to the insular cortex, the part of the brain that involves mindfulness and self-awareness.”
 

Symptom reduction

In the completer sample of 17 participants, mean scores on anxiety and depression symptoms fell significantly from baseline to 4 weeks (all P < .01). For example, the GAD-7 mean score fell from 14.3 to 7.1 and the BDI mean score from 30.6 to 14.8.

The study also showed that mindfulness was enhanced. The MAIA total score increased from 83.1 to 93.5 (P = .014).

Device users had increased alpha and theta brainwave activity, findings that “go along with the concept of decreased anxiety,” said Dr. Carpenter. She noted a recent study of the same patient population showed the device enhanced functional brain connectivity.

This current study was too small to pick up signals showing the device was effective in any particular subpopulation, said Dr. Carpenter.

Unlike other stimulation interventions that require clinic visits, patients use the MATT in the comfort of their own home and at their own convenience.

However, there are still questions surrounding the use of the noninvasive device. For example, said Dr. Carpenter, it’s unclear if it would be more effective if combined with psychotherapy or whether patients can use it while sleeping and driving. A next step could be a sham-controlled trial, she said.

The study was supported by Affect Neuro, developer of MATT therapy, and the National Institute of General Medical Sciences. Dr. Carpenter reports receiving a consultancy fee from Affect Neuro.

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

An at-home investigational device is a promising noninvasive therapeutic approach for anxiety disorders, results from an open-label pilot trial suggest.

The small study showed users of the Mechanical Affective Touch Therapy (MATT) had improved anxiety and depression symptoms, which corresponded to positive changes in alpha and theta oscillatory activity.

Butler Hospital

Robust safety profile

Therapeutic noninvasive peripheral nerve stimulation is under investigation for anxiety as well as pain and depression. Nerve activation is achieved by delivering electrical or mechanical energy, although most devices to date have used electrical stimulation.

Although electrical stimulation is considered low risk, mechanical stimulation that activates somatosensory pathways has an even more robust safety profile, the investigators note.

The MATT device targets C-tactile fibers (CT) specialized unmyelinated Group C peripheral nerve fibers that fire when stroked at velocities perceived as pleasurable or comforting.

To use the device, participants wear a headset with a small vibrating piece that sits on the mastoid bone behind each ear. These pieces deliver gentle vibrations that can be adjusted by patients.  

During development of the MATT stimulation, researchers noted that an isochronic 10 Hz wave, cycling 2 seconds on and 2 seconds off, induced a state of relaxation and increased occipital alpha oscillations in pilot study participants.

The current study was designed to confirm preliminary efficacy and feasibility signals. The sample included 22 patients (mean age 37.3 years, 72.7% female, 77.3% White). All study participants were diagnosed with an anxiety disorder and had at least moderately severe anxiety symptoms. Some also had symptoms of panic or depression.

Many participants were on medications that weren’t effective, and they wanted to find a nondrug method of relieving their symptoms, said Dr. Carpenter.
 

What’s the mechanism?

Participants learned how to administer the stimulation and adjust the intensity of vibrations to a level where it was consistently detectable but not uncomfortable. Then they received a MATT device to use at home at least twice daily for 20 minutes.

Patients kept daily diaries documenting device use, adverse effects, and technological problems. In-person assessments were held at 2 and 4 weeks.

Researchers collected resting EEG immediately before, and after, the second stimulation session and again following 4 weeks of MATT use.

At baseline and after 2 and 4 weeks, patients self-reported anxiety using the 7-item Generalized Anxiety Disorder (GAD-7) scale, depression with the Beck Depression Inventory (BDI), and stress using the Perceived Stress Scale (PSS). They also reported symptoms with the Depression, Anxiety, Stress Scale (DASS).

Researchers also investigated “interoceptive awareness” or being mindful of your body and internal feelings. For this, they had participants complete the 32-item Multidimensional Assessment of Interoceptive Awareness pre- and post treatment.

Interoceptive awareness “is a whole new area of interest in neuroscience and brain health,” said Dr. Carpenter. “The hypothesis was that one way this device might work is that vibrations would travel to the insular cortex, the part of the brain that involves mindfulness and self-awareness.”
 

Symptom reduction

In the completer sample of 17 participants, mean scores on anxiety and depression symptoms fell significantly from baseline to 4 weeks (all P < .01). For example, the GAD-7 mean score fell from 14.3 to 7.1 and the BDI mean score from 30.6 to 14.8.

The study also showed that mindfulness was enhanced. The MAIA total score increased from 83.1 to 93.5 (P = .014).

Device users had increased alpha and theta brainwave activity, findings that “go along with the concept of decreased anxiety,” said Dr. Carpenter. She noted a recent study of the same patient population showed the device enhanced functional brain connectivity.

This current study was too small to pick up signals showing the device was effective in any particular subpopulation, said Dr. Carpenter.

Unlike other stimulation interventions that require clinic visits, patients use the MATT in the comfort of their own home and at their own convenience.

However, there are still questions surrounding the use of the noninvasive device. For example, said Dr. Carpenter, it’s unclear if it would be more effective if combined with psychotherapy or whether patients can use it while sleeping and driving. A next step could be a sham-controlled trial, she said.

The study was supported by Affect Neuro, developer of MATT therapy, and the National Institute of General Medical Sciences. Dr. Carpenter reports receiving a consultancy fee from Affect Neuro.

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

Elevated concentrations of carbon monoxide (CO) due to air pollution increases the risk of epileptic seizures, a unique new study suggests.

The link between daily outdoor CO exposure and seizure risk was particularly evident for subclinical seizures – those in patients with abnormal electroencephalography (EEG) signals but no clinical symptoms.

“Our findings suggest that people with epilepsy should avoid high CO exposure to reduce potential seizure risk,” said study investigator Zhuying Chen, PhD candidate, department of biomedical engineering, University of Melbourne.

The study was published online in Epilepsia.
 

Pollution’s impact on brain health

Emerging evidence indicates air pollution affects brain health and may increase the risk of hospitalization or outpatient visits for epilepsy. However, little is known about the effect of pollution on the occurrence of epileptic seizures.

The study used two independent long-term seizure datasets – the NeuroVista (NV) study and the Seer App seizure diary (SD). In the NeuroVista study, researchers recorded continuous intracranial iEEG from patients with refractory focal epilepsy who had been implanted with a personal seizure advisory device that wirelessly recorded seizures on an external device.

The SD dataset included diaries documenting self-reported seizures, seizure cycles, and medication adherence.

Researchers collected data on hourly concentrations of outdoor CO, nitrogen dioxide (NO₂), particulate matter of 10 μm or less in diameter (PM₁₀), ozone (O₃), and sulfur dioxide (SO₂). The levels were measured at air quality monitoring stations in Australia.

Investigators aggregated hourly observations into daily mean data. All daily concentrations of CO and SO₂ and at least 95% of daily concentrations of NO₂, O₃, and PM₁₀ were within Australian air quality standards, said Mr. Chen.

The study included 49 participants, with epilepsy data on 15 patients in the NeuroVista study and on 34 from the SD dataset.

Overall, 6,692 epileptic seizures on 3,639 seizure days were recorded during 23,349 follow-up days from 2010 to 2012 (NV dataset) and 2018 to 2021 (SD dataset).

The investigators found a significant positive association between CO concentrations and epileptic seizure risks. The relative risk (RR) was 1.04 (95% confidence interval, 1.01–1.07; P < .01) for an interquartile range (IQR) increase of CO (0.13 parts per million).
 

Sex differences

There were no significant relationships for the other four air pollutants. However, Mr. Chen noted that Australia has very low air pollution levels; most usually are within World Health Organization air quality guidelines.

“Our findings may not be generalized to other countries with high air pollution levels,” said Mr. Chen. He noted that the relatively small number of patients in the study may limit the statistical power to detect some associations.

The study showed that females had a significantly increased risk of epileptic seizures when exposed to elevated CO (RR, 1.05; 95% CI, 1.01–1.08; P < .05) and NO₂ (RR, 1.09; 95% CI, 1.01–1.16; P < .05) concentrations. There were no significant associations in males for any air pollutants.

Differences in outdoor activities and behaviors such as smoking and exercise may lead to variations in environmental exposure and help explain the sex differences, said Mr. Chen. These differences may also be due to the study’s limited sample size.

Analyzing the two datasets separately, the researchers found there was a significant association between CO concentration and epileptic seizure risk in the NV dataset (RR, 1.10; 95% CI, 1.03–1.17; P < .01).

There were no significant associations in the SD dataset for any air pollutants. This may be because only clinical seizures – those associated with evident symptoms – are self-reported, said Mr. Chen. He also noted that seizure diaries may be unreliable.

In the NV dataset, the epileptic seizure risk was significantly increased when only subclinical seizures were considered (RR, 1.20; 95% CI, 1.12–1.28; P < .001) for an IQR increase of CO concentration.

The risk was significantly decreased by 13% for subclinical seizures with an IQR increase of PM₁₀ and by 9% for subclinical seizures with an IQR increase of SO₂ concentrations.

These negative associations should be interpreted with caution, inasmuch as the associations were not robust in subsequent subgroup and sensitivity analyses, said Mr. Chen.

There were no significant associations when considering clinical seizures for any air pollutants.

The positive association for subclinical but not clinical seizures suggests that low-level CO exposure may not be strong enough to directly trigger clinical seizures, said Mr. Chen.

Although previous research has demonstrated adverse neurologic effects of exposure to air pollutants, most studies were based on hospital databases or registers. Thus, they may have missed seizures that did not lead to hospital admission.
 

Unclear mechanism

The exact mechanisms linking air pollution to seizures are unclear but probably involve the synergistic interaction of multiple pathways, said Mr. Chen. “Air pollution may affect brain metabolism, alter the immune response of the brain, and induce oxidative stress and neuroinflammation, causing the brain to be more susceptible to seizures,” he noted.

This is the first study to investigate seizure rates through intracranial EEG signals and self-reported seizure diaries. It’s also the first to look into the impact of pollutants at low concentration levels on subclinical seizures.

However, the study has some limitations. Self-reported seizures in the SD dataset might underestimate the influence of air pollution on seizures. The study used postal codes as proxies for exposure to pollution, which could introduce measurement errors and underestimate associations.

In addition, Mr. Chen noted that seizures from the NeuroVista dataset were recorded from patients with drug-resistant focal epilepsy. “Whether our findings can be generalized to other epilepsy types needs further investigation.”

The study could have important clinical and public health implications. For example, said Mr. Chen, it’s possible that seizure risk could be reduced through behavioral interventions, such as avoiding being outside or using an air filtration system when pollutant levels are high.

“Clinicians could counsel their patients to avoid the potential risk of high carbon monoxide exposure,” he said.

CO exposure could be a new factor for seizure risk forecasting, which could reduce the uncertainty of seizures and help guide epilepsy management, Mr. Chen added.

The study was supported by the Melbourne Monash Consciousness Research Seed Funding and an Australian National Health and Medical Research Council Ideas grant. Mr. Chen has disclosed no relevant financial relationships.

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

Elevated concentrations of carbon monoxide (CO) due to air pollution increases the risk of epileptic seizures, a unique new study suggests.

The link between daily outdoor CO exposure and seizure risk was particularly evident for subclinical seizures – those in patients with abnormal electroencephalography (EEG) signals but no clinical symptoms.

“Our findings suggest that people with epilepsy should avoid high CO exposure to reduce potential seizure risk,” said study investigator Zhuying Chen, PhD candidate, department of biomedical engineering, University of Melbourne.

The study was published online in Epilepsia.
 

Pollution’s impact on brain health

Emerging evidence indicates air pollution affects brain health and may increase the risk of hospitalization or outpatient visits for epilepsy. However, little is known about the effect of pollution on the occurrence of epileptic seizures.

The study used two independent long-term seizure datasets – the NeuroVista (NV) study and the Seer App seizure diary (SD). In the NeuroVista study, researchers recorded continuous intracranial iEEG from patients with refractory focal epilepsy who had been implanted with a personal seizure advisory device that wirelessly recorded seizures on an external device.

The SD dataset included diaries documenting self-reported seizures, seizure cycles, and medication adherence.

Researchers collected data on hourly concentrations of outdoor CO, nitrogen dioxide (NO₂), particulate matter of 10 μm or less in diameter (PM₁₀), ozone (O₃), and sulfur dioxide (SO₂). The levels were measured at air quality monitoring stations in Australia.

Investigators aggregated hourly observations into daily mean data. All daily concentrations of CO and SO₂ and at least 95% of daily concentrations of NO₂, O₃, and PM₁₀ were within Australian air quality standards, said Mr. Chen.

The study included 49 participants, with epilepsy data on 15 patients in the NeuroVista study and on 34 from the SD dataset.

Overall, 6,692 epileptic seizures on 3,639 seizure days were recorded during 23,349 follow-up days from 2010 to 2012 (NV dataset) and 2018 to 2021 (SD dataset).

The investigators found a significant positive association between CO concentrations and epileptic seizure risks. The relative risk (RR) was 1.04 (95% confidence interval, 1.01–1.07; P < .01) for an interquartile range (IQR) increase of CO (0.13 parts per million).
 

Sex differences

There were no significant relationships for the other four air pollutants. However, Mr. Chen noted that Australia has very low air pollution levels; most usually are within World Health Organization air quality guidelines.

“Our findings may not be generalized to other countries with high air pollution levels,” said Mr. Chen. He noted that the relatively small number of patients in the study may limit the statistical power to detect some associations.

The study showed that females had a significantly increased risk of epileptic seizures when exposed to elevated CO (RR, 1.05; 95% CI, 1.01–1.08; P < .05) and NO₂ (RR, 1.09; 95% CI, 1.01–1.16; P < .05) concentrations. There were no significant associations in males for any air pollutants.

Differences in outdoor activities and behaviors such as smoking and exercise may lead to variations in environmental exposure and help explain the sex differences, said Mr. Chen. These differences may also be due to the study’s limited sample size.

Analyzing the two datasets separately, the researchers found there was a significant association between CO concentration and epileptic seizure risk in the NV dataset (RR, 1.10; 95% CI, 1.03–1.17; P < .01).

There were no significant associations in the SD dataset for any air pollutants. This may be because only clinical seizures – those associated with evident symptoms – are self-reported, said Mr. Chen. He also noted that seizure diaries may be unreliable.

In the NV dataset, the epileptic seizure risk was significantly increased when only subclinical seizures were considered (RR, 1.20; 95% CI, 1.12–1.28; P < .001) for an IQR increase of CO concentration.

The risk was significantly decreased by 13% for subclinical seizures with an IQR increase of PM₁₀ and by 9% for subclinical seizures with an IQR increase of SO₂ concentrations.

These negative associations should be interpreted with caution, inasmuch as the associations were not robust in subsequent subgroup and sensitivity analyses, said Mr. Chen.

There were no significant associations when considering clinical seizures for any air pollutants.

The positive association for subclinical but not clinical seizures suggests that low-level CO exposure may not be strong enough to directly trigger clinical seizures, said Mr. Chen.

Although previous research has demonstrated adverse neurologic effects of exposure to air pollutants, most studies were based on hospital databases or registers. Thus, they may have missed seizures that did not lead to hospital admission.
 

Unclear mechanism

The exact mechanisms linking air pollution to seizures are unclear but probably involve the synergistic interaction of multiple pathways, said Mr. Chen. “Air pollution may affect brain metabolism, alter the immune response of the brain, and induce oxidative stress and neuroinflammation, causing the brain to be more susceptible to seizures,” he noted.

This is the first study to investigate seizure rates through intracranial EEG signals and self-reported seizure diaries. It’s also the first to look into the impact of pollutants at low concentration levels on subclinical seizures.

However, the study has some limitations. Self-reported seizures in the SD dataset might underestimate the influence of air pollution on seizures. The study used postal codes as proxies for exposure to pollution, which could introduce measurement errors and underestimate associations.

In addition, Mr. Chen noted that seizures from the NeuroVista dataset were recorded from patients with drug-resistant focal epilepsy. “Whether our findings can be generalized to other epilepsy types needs further investigation.”

The study could have important clinical and public health implications. For example, said Mr. Chen, it’s possible that seizure risk could be reduced through behavioral interventions, such as avoiding being outside or using an air filtration system when pollutant levels are high.

“Clinicians could counsel their patients to avoid the potential risk of high carbon monoxide exposure,” he said.

CO exposure could be a new factor for seizure risk forecasting, which could reduce the uncertainty of seizures and help guide epilepsy management, Mr. Chen added.

The study was supported by the Melbourne Monash Consciousness Research Seed Funding and an Australian National Health and Medical Research Council Ideas grant. Mr. Chen has disclosed no relevant financial relationships.

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

Elevated concentrations of carbon monoxide (CO) due to air pollution increases the risk of epileptic seizures, a unique new study suggests.

The link between daily outdoor CO exposure and seizure risk was particularly evident for subclinical seizures – those in patients with abnormal electroencephalography (EEG) signals but no clinical symptoms.

“Our findings suggest that people with epilepsy should avoid high CO exposure to reduce potential seizure risk,” said study investigator Zhuying Chen, PhD candidate, department of biomedical engineering, University of Melbourne.

The study was published online in Epilepsia.
 

Pollution’s impact on brain health

Emerging evidence indicates air pollution affects brain health and may increase the risk of hospitalization or outpatient visits for epilepsy. However, little is known about the effect of pollution on the occurrence of epileptic seizures.

The study used two independent long-term seizure datasets – the NeuroVista (NV) study and the Seer App seizure diary (SD). In the NeuroVista study, researchers recorded continuous intracranial iEEG from patients with refractory focal epilepsy who had been implanted with a personal seizure advisory device that wirelessly recorded seizures on an external device.

The SD dataset included diaries documenting self-reported seizures, seizure cycles, and medication adherence.

Researchers collected data on hourly concentrations of outdoor CO, nitrogen dioxide (NO₂), particulate matter of 10 μm or less in diameter (PM₁₀), ozone (O₃), and sulfur dioxide (SO₂). The levels were measured at air quality monitoring stations in Australia.

Investigators aggregated hourly observations into daily mean data. All daily concentrations of CO and SO₂ and at least 95% of daily concentrations of NO₂, O₃, and PM₁₀ were within Australian air quality standards, said Mr. Chen.

The study included 49 participants, with epilepsy data on 15 patients in the NeuroVista study and on 34 from the SD dataset.

Overall, 6,692 epileptic seizures on 3,639 seizure days were recorded during 23,349 follow-up days from 2010 to 2012 (NV dataset) and 2018 to 2021 (SD dataset).

The investigators found a significant positive association between CO concentrations and epileptic seizure risks. The relative risk (RR) was 1.04 (95% confidence interval, 1.01–1.07; P < .01) for an interquartile range (IQR) increase of CO (0.13 parts per million).
 

Sex differences

There were no significant relationships for the other four air pollutants. However, Mr. Chen noted that Australia has very low air pollution levels; most usually are within World Health Organization air quality guidelines.

“Our findings may not be generalized to other countries with high air pollution levels,” said Mr. Chen. He noted that the relatively small number of patients in the study may limit the statistical power to detect some associations.

The study showed that females had a significantly increased risk of epileptic seizures when exposed to elevated CO (RR, 1.05; 95% CI, 1.01–1.08; P < .05) and NO₂ (RR, 1.09; 95% CI, 1.01–1.16; P < .05) concentrations. There were no significant associations in males for any air pollutants.

Differences in outdoor activities and behaviors such as smoking and exercise may lead to variations in environmental exposure and help explain the sex differences, said Mr. Chen. These differences may also be due to the study’s limited sample size.

Analyzing the two datasets separately, the researchers found there was a significant association between CO concentration and epileptic seizure risk in the NV dataset (RR, 1.10; 95% CI, 1.03–1.17; P < .01).

There were no significant associations in the SD dataset for any air pollutants. This may be because only clinical seizures – those associated with evident symptoms – are self-reported, said Mr. Chen. He also noted that seizure diaries may be unreliable.

In the NV dataset, the epileptic seizure risk was significantly increased when only subclinical seizures were considered (RR, 1.20; 95% CI, 1.12–1.28; P < .001) for an IQR increase of CO concentration.

The risk was significantly decreased by 13% for subclinical seizures with an IQR increase of PM₁₀ and by 9% for subclinical seizures with an IQR increase of SO₂ concentrations.

These negative associations should be interpreted with caution, inasmuch as the associations were not robust in subsequent subgroup and sensitivity analyses, said Mr. Chen.

There were no significant associations when considering clinical seizures for any air pollutants.

The positive association for subclinical but not clinical seizures suggests that low-level CO exposure may not be strong enough to directly trigger clinical seizures, said Mr. Chen.

Although previous research has demonstrated adverse neurologic effects of exposure to air pollutants, most studies were based on hospital databases or registers. Thus, they may have missed seizures that did not lead to hospital admission.
 

Unclear mechanism

The exact mechanisms linking air pollution to seizures are unclear but probably involve the synergistic interaction of multiple pathways, said Mr. Chen. “Air pollution may affect brain metabolism, alter the immune response of the brain, and induce oxidative stress and neuroinflammation, causing the brain to be more susceptible to seizures,” he noted.

This is the first study to investigate seizure rates through intracranial EEG signals and self-reported seizure diaries. It’s also the first to look into the impact of pollutants at low concentration levels on subclinical seizures.

However, the study has some limitations. Self-reported seizures in the SD dataset might underestimate the influence of air pollution on seizures. The study used postal codes as proxies for exposure to pollution, which could introduce measurement errors and underestimate associations.

In addition, Mr. Chen noted that seizures from the NeuroVista dataset were recorded from patients with drug-resistant focal epilepsy. “Whether our findings can be generalized to other epilepsy types needs further investigation.”

The study could have important clinical and public health implications. For example, said Mr. Chen, it’s possible that seizure risk could be reduced through behavioral interventions, such as avoiding being outside or using an air filtration system when pollutant levels are high.

“Clinicians could counsel their patients to avoid the potential risk of high carbon monoxide exposure,” he said.

CO exposure could be a new factor for seizure risk forecasting, which could reduce the uncertainty of seizures and help guide epilepsy management, Mr. Chen added.

The study was supported by the Melbourne Monash Consciousness Research Seed Funding and an Australian National Health and Medical Research Council Ideas grant. Mr. Chen has disclosed no relevant financial relationships.

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

Researchers are increasingly turning their attention to virtual reality (VR) for the treatment of psychiatric disorders in older adults.

Recent studies have highlighted the usefulness of VR in treating depression and loneliness in older patients who may be socially isolated because of their age, comorbidities, or the COVID-19 pandemic.

“The unique capability of virtual reality to create an immersive and engaging setting is an exciting opportunity for geriatric psychiatry,” Harmehr Sekhon, PhD, postdoctoral research fellow, Lady Davis Institute/Jewish General Hospital, McGill University, Montreal, and McLean Hospital, Harvard Medical School, Boston, told this news organization.

Because VR can be personalized and tailored for each patient, it represents “a cutting-edge technology” for novel applications, Dr. Sekhon said.

One novel approach involves using VR to administer a mindfulness intervention in older adults. Dr. Sekhon shared information on her own mindfulness study and on other developments in VR and telemedicine at the American Association for Geriatric Psychiatry annual meeting.
 

Potential bridging tool

As the population ages, the prevalence of mental health disorders increases. Telemedicine has proved to be a potential “bridge” to address the health care needs of older adults, Dr. Sekhon noted.

She cited her systematic review of telemedicine for older adults with dementia during COVID-19. Results showed that telemedicine was a “beneficial approach” to assisting these individuals and that it increased accessibility, said Dr. Sekhon.

In addition, a survey published last year showed that 87% of Americans in general want to continue using telehealth services after the pandemic. Most respondents agreed that telehealth had made it easier to get the care they needed. They also reported having received the same level of care via telehealth as with in-person care.

A growing body of research shows that VR has “positive influences on mood and well-being, cognition, pain management, [and] treatment of phobias in younger adults,” Dr. Sekhon said. She added that there is evidence that VR is feasible for older adults, with applications in cognitive disorders.

She cited a recent systematic review of 55 studies that assessed the impact of different types of VR on mental health in older adults. The results showed that VR could be helpful in screening for cognitive impairment – and it was comparable to some paper-based assessment. It was also useful as a training tool for those with cognitive impairment.

Examples of VR interventions that can be used to treat cognitive impairment include “virtual cities, kitchens, supermarkets,” Dr. Sekhon noted.

The technology is increasingly being used as a tool to deliver psychotherapy, in which patient engagement is “a key determinant” of outcomes, she added. “Virtual reality is a cutting-edge, engaging, and immersive technique to administer psychotherapy,” she said.

Such VR approaches are proving successful in older patients. Dr. Sekhon highlighted the case of an 85-year-old woman who engaged in ten sessions of psychodynamic psychotherapy that targeted persistent dysthymia and negativistic mood. The case was part of a proof-of-concept study published in the May issue of the American Journal of Geriatric Psychiatry.

Dr. Sekhon noted the intervention was well tolerated and was associated with minimal side effects.
 

VR-based meditation

Dr. Sekhon and her colleagues are now conducting a randomized controlled trial of VR meditation in older adults. VR-based meditation has been shown to increase relaxation and to decrease anxiety, sadness, and anger in younger adults. However, it has not been studied in the geriatric population.

The pilot study is assessing the feasibility and tolerability of VR meditation for older adults and its effects on stress, anxiety, depression, sleep, and quality of life. The study involves 30 adults aged 60 years and older.

Participants receive either 15-minute VR mindfulness meditation sessions twice a week for 4 weeks or are on a control wait list. The meditation sessions are user friendly and focus on breath meditation and body scans, Dr. Sekhon reported.

Because participants are older and balance is a concern, safety steps are incorporated into the sessions. “We ensure they’re doing this in a seated position, in a chair with arm rests, so that they’re very stable and there’s no risk of falls,” said Dr. Sekhon.

Another concern with VR is motion sickness, she noted. “It’s pretty minimal, but the best way we found so far is giving older adults time to adapt and feel comfortable with the VR,” she said. From the first session, participants learn how to put on the device and are checked to make sure they are comfortable with the process. To help them get used to everything, video and audio are not included during the first session.

Dr. Sekhon noted that results from the study are expected later this year.

In addition to mindfulness, researchers are using VR to deliver other established interventions, such as exposure therapy – and are implementing these approaches in varied environments, including long-term and palliative care settings.

VR-related technology is constantly improving and is becoming easier to use and more affordable, said Dr. Sekhon. She noted that the simplest devices that rely on smartphones cost as little as $15.

Although VR in older adults is promising, there are barriers to its adoption and use in research, she noted. For example, older adults may have cognitive, visual, or hearing impairments. They may have limited digital literacy, and/or they may not have access to the required technology.

These barriers can be overcome through workarounds, including providing instructional videos and digital literacy assistance via Zoom and working with community partners to facilitate study recruitment of older patients, Dr. Sekhon said.

Dr. Sekhon’s research is funded by the Canadian Institutes of Health Research and the Fonds de recherche du Quebec Sante.

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

Researchers are increasingly turning their attention to virtual reality (VR) for the treatment of psychiatric disorders in older adults.

Recent studies have highlighted the usefulness of VR in treating depression and loneliness in older patients who may be socially isolated because of their age, comorbidities, or the COVID-19 pandemic.

“The unique capability of virtual reality to create an immersive and engaging setting is an exciting opportunity for geriatric psychiatry,” Harmehr Sekhon, PhD, postdoctoral research fellow, Lady Davis Institute/Jewish General Hospital, McGill University, Montreal, and McLean Hospital, Harvard Medical School, Boston, told this news organization.

Because VR can be personalized and tailored for each patient, it represents “a cutting-edge technology” for novel applications, Dr. Sekhon said.

One novel approach involves using VR to administer a mindfulness intervention in older adults. Dr. Sekhon shared information on her own mindfulness study and on other developments in VR and telemedicine at the American Association for Geriatric Psychiatry annual meeting.
 

Potential bridging tool

As the population ages, the prevalence of mental health disorders increases. Telemedicine has proved to be a potential “bridge” to address the health care needs of older adults, Dr. Sekhon noted.

She cited her systematic review of telemedicine for older adults with dementia during COVID-19. Results showed that telemedicine was a “beneficial approach” to assisting these individuals and that it increased accessibility, said Dr. Sekhon.

In addition, a survey published last year showed that 87% of Americans in general want to continue using telehealth services after the pandemic. Most respondents agreed that telehealth had made it easier to get the care they needed. They also reported having received the same level of care via telehealth as with in-person care.

A growing body of research shows that VR has “positive influences on mood and well-being, cognition, pain management, [and] treatment of phobias in younger adults,” Dr. Sekhon said. She added that there is evidence that VR is feasible for older adults, with applications in cognitive disorders.

She cited a recent systematic review of 55 studies that assessed the impact of different types of VR on mental health in older adults. The results showed that VR could be helpful in screening for cognitive impairment – and it was comparable to some paper-based assessment. It was also useful as a training tool for those with cognitive impairment.

Examples of VR interventions that can be used to treat cognitive impairment include “virtual cities, kitchens, supermarkets,” Dr. Sekhon noted.

The technology is increasingly being used as a tool to deliver psychotherapy, in which patient engagement is “a key determinant” of outcomes, she added. “Virtual reality is a cutting-edge, engaging, and immersive technique to administer psychotherapy,” she said.

Such VR approaches are proving successful in older patients. Dr. Sekhon highlighted the case of an 85-year-old woman who engaged in ten sessions of psychodynamic psychotherapy that targeted persistent dysthymia and negativistic mood. The case was part of a proof-of-concept study published in the May issue of the American Journal of Geriatric Psychiatry.

Dr. Sekhon noted the intervention was well tolerated and was associated with minimal side effects.
 

VR-based meditation

Dr. Sekhon and her colleagues are now conducting a randomized controlled trial of VR meditation in older adults. VR-based meditation has been shown to increase relaxation and to decrease anxiety, sadness, and anger in younger adults. However, it has not been studied in the geriatric population.

The pilot study is assessing the feasibility and tolerability of VR meditation for older adults and its effects on stress, anxiety, depression, sleep, and quality of life. The study involves 30 adults aged 60 years and older.

Participants receive either 15-minute VR mindfulness meditation sessions twice a week for 4 weeks or are on a control wait list. The meditation sessions are user friendly and focus on breath meditation and body scans, Dr. Sekhon reported.

Because participants are older and balance is a concern, safety steps are incorporated into the sessions. “We ensure they’re doing this in a seated position, in a chair with arm rests, so that they’re very stable and there’s no risk of falls,” said Dr. Sekhon.

Another concern with VR is motion sickness, she noted. “It’s pretty minimal, but the best way we found so far is giving older adults time to adapt and feel comfortable with the VR,” she said. From the first session, participants learn how to put on the device and are checked to make sure they are comfortable with the process. To help them get used to everything, video and audio are not included during the first session.

Dr. Sekhon noted that results from the study are expected later this year.

In addition to mindfulness, researchers are using VR to deliver other established interventions, such as exposure therapy – and are implementing these approaches in varied environments, including long-term and palliative care settings.

VR-related technology is constantly improving and is becoming easier to use and more affordable, said Dr. Sekhon. She noted that the simplest devices that rely on smartphones cost as little as $15.

Although VR in older adults is promising, there are barriers to its adoption and use in research, she noted. For example, older adults may have cognitive, visual, or hearing impairments. They may have limited digital literacy, and/or they may not have access to the required technology.

These barriers can be overcome through workarounds, including providing instructional videos and digital literacy assistance via Zoom and working with community partners to facilitate study recruitment of older patients, Dr. Sekhon said.

Dr. Sekhon’s research is funded by the Canadian Institutes of Health Research and the Fonds de recherche du Quebec Sante.

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

Researchers are increasingly turning their attention to virtual reality (VR) for the treatment of psychiatric disorders in older adults.

Recent studies have highlighted the usefulness of VR in treating depression and loneliness in older patients who may be socially isolated because of their age, comorbidities, or the COVID-19 pandemic.

“The unique capability of virtual reality to create an immersive and engaging setting is an exciting opportunity for geriatric psychiatry,” Harmehr Sekhon, PhD, postdoctoral research fellow, Lady Davis Institute/Jewish General Hospital, McGill University, Montreal, and McLean Hospital, Harvard Medical School, Boston, told this news organization.

Because VR can be personalized and tailored for each patient, it represents “a cutting-edge technology” for novel applications, Dr. Sekhon said.

One novel approach involves using VR to administer a mindfulness intervention in older adults. Dr. Sekhon shared information on her own mindfulness study and on other developments in VR and telemedicine at the American Association for Geriatric Psychiatry annual meeting.
 

Potential bridging tool

As the population ages, the prevalence of mental health disorders increases. Telemedicine has proved to be a potential “bridge” to address the health care needs of older adults, Dr. Sekhon noted.

She cited her systematic review of telemedicine for older adults with dementia during COVID-19. Results showed that telemedicine was a “beneficial approach” to assisting these individuals and that it increased accessibility, said Dr. Sekhon.

In addition, a survey published last year showed that 87% of Americans in general want to continue using telehealth services after the pandemic. Most respondents agreed that telehealth had made it easier to get the care they needed. They also reported having received the same level of care via telehealth as with in-person care.

A growing body of research shows that VR has “positive influences on mood and well-being, cognition, pain management, [and] treatment of phobias in younger adults,” Dr. Sekhon said. She added that there is evidence that VR is feasible for older adults, with applications in cognitive disorders.

She cited a recent systematic review of 55 studies that assessed the impact of different types of VR on mental health in older adults. The results showed that VR could be helpful in screening for cognitive impairment – and it was comparable to some paper-based assessment. It was also useful as a training tool for those with cognitive impairment.

Examples of VR interventions that can be used to treat cognitive impairment include “virtual cities, kitchens, supermarkets,” Dr. Sekhon noted.

The technology is increasingly being used as a tool to deliver psychotherapy, in which patient engagement is “a key determinant” of outcomes, she added. “Virtual reality is a cutting-edge, engaging, and immersive technique to administer psychotherapy,” she said.

Such VR approaches are proving successful in older patients. Dr. Sekhon highlighted the case of an 85-year-old woman who engaged in ten sessions of psychodynamic psychotherapy that targeted persistent dysthymia and negativistic mood. The case was part of a proof-of-concept study published in the May issue of the American Journal of Geriatric Psychiatry.

Dr. Sekhon noted the intervention was well tolerated and was associated with minimal side effects.
 

VR-based meditation

Dr. Sekhon and her colleagues are now conducting a randomized controlled trial of VR meditation in older adults. VR-based meditation has been shown to increase relaxation and to decrease anxiety, sadness, and anger in younger adults. However, it has not been studied in the geriatric population.

The pilot study is assessing the feasibility and tolerability of VR meditation for older adults and its effects on stress, anxiety, depression, sleep, and quality of life. The study involves 30 adults aged 60 years and older.

Participants receive either 15-minute VR mindfulness meditation sessions twice a week for 4 weeks or are on a control wait list. The meditation sessions are user friendly and focus on breath meditation and body scans, Dr. Sekhon reported.

Because participants are older and balance is a concern, safety steps are incorporated into the sessions. “We ensure they’re doing this in a seated position, in a chair with arm rests, so that they’re very stable and there’s no risk of falls,” said Dr. Sekhon.

Another concern with VR is motion sickness, she noted. “It’s pretty minimal, but the best way we found so far is giving older adults time to adapt and feel comfortable with the VR,” she said. From the first session, participants learn how to put on the device and are checked to make sure they are comfortable with the process. To help them get used to everything, video and audio are not included during the first session.

Dr. Sekhon noted that results from the study are expected later this year.

In addition to mindfulness, researchers are using VR to deliver other established interventions, such as exposure therapy – and are implementing these approaches in varied environments, including long-term and palliative care settings.

VR-related technology is constantly improving and is becoming easier to use and more affordable, said Dr. Sekhon. She noted that the simplest devices that rely on smartphones cost as little as $15.

Although VR in older adults is promising, there are barriers to its adoption and use in research, she noted. For example, older adults may have cognitive, visual, or hearing impairments. They may have limited digital literacy, and/or they may not have access to the required technology.

These barriers can be overcome through workarounds, including providing instructional videos and digital literacy assistance via Zoom and working with community partners to facilitate study recruitment of older patients, Dr. Sekhon said.

Dr. Sekhon’s research is funded by the Canadian Institutes of Health Research and the Fonds de recherche du Quebec Sante.

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

A novel virtual reality (VR) intervention significantly reduces agoraphobia in patients with psychosis, new research suggests.

The cognitive-behavioral therapy–based treatment was particularly effective for patients with the highest level of avoidance of everyday situations.

Courtesy University of Oxford

“Virtual reality is an inherently therapeutic medium which could be extremely useful in mental health services,” study investigator Daniel Freeman, PhD, DClinPsy, professor of clinical psychology, University of Oxford (England), told this news organization.  “This intervention is coming; the question really is when.”

The study was published online  in The Lancet Psychiatry.
 

Real-world feel

Immersive VR involves interactive three-dimensional computer-generated environments that produce the sensation of being in the real world.

For patients with psychosis, dealing with the real world can be an anxious experience, particularly if they have verbal or auditory hallucinations.

Some may develop agoraphobia and start to avoid places or situations. A virtual environment allows patients to practice dealing with situations that make them anxious or uncomfortable and to learn to reengage in everyday situations.

The study included 346 patients diagnosed with schizophrenia or a related disorder. The mean age of the patients was 37.2 years (67% were men, 85% were White). Most were single and unemployed. All were receiving treatment for psychosis and had difficulty going out because of anxiety.

The researchers randomly assigned 174 participants to an automated VR cognitive therapy intervention (gameChange) plus usual care and 172 to usual care alone. Trial assessors were blinded to group allocation.

The gameChange intervention was delivered in six sessions that were conducted over a 6-week period. Each session involved 30 minutes of VR.

A session begins when participants enter the virtual therapist’s office. They are met by a coach who guides them through the therapy. They can choose from among six VR social situations. These include a cafe, a general practice waiting room, a pub, a bus, opening the front door of their home onto the street, or entering a small local shop.

Each scenario has five levels of difficulty that are based on the number and proximity of people in the social situation and the degree of social interaction. Users can work their way through these various levels.

The virtual sessions took place in patients’ homes in about 50% of cases; the remainder were conducted in the clinic. A mental health worker was in the room during the therapy.

Between virtual sessions, participants were encouraged to apply what they learned in the real world, for example, by spending time in a pub.

Usual care typically included regular visits from a community mental health worker and occasional outpatient appointments with a psychiatrist.
 

Widely applicable?

The primary outcome was the eight-item Oxford Agoraphobic Avoidance Scale (O-AS) questionnaire. This scale assesses distress and avoidance related to performing increasingly difficult everyday tasks.

The researchers assessed patients at baseline, at the conclusion of the 6-week treatment, and at 26 weeks.

Compared with the group that received usual care alone, the VR therapy group demonstrated a significant reduction in both agoraphobic avoidance (O-AS adjusted mean difference, -0.47; 95% confidence interval [CI], –0.88 to –0.06; Cohen’s d, –0.18; P = .026) and distress (–4.33; 95% CI, –7.78 to –0.87; Cohen’s d, –0.26; P = .014) at 6 weeks.

This translates to being able to do about 1.5 more activities on the O-AS, such as going to a shopping center alone, said Dr. Freeman.

Further analyses showed that VR therapy was especially effective for patients with severe agoraphobia. On average, these patients could complete two more O-AS activities at 26 weeks, said Dr. Freeman.

The authors believe the intervention worked by reducing defense behaviors, such as avoiding eye contact and fearful thoughts.

There was no significant difference in occurrence of adverse events between the study groups. These events, which were mild, transient, and did not affect the outcome, included side effects such as claustrophobia when using headsets.

The intervention would likely work for patients with agoraphobia who do not have psychosis, said Dr. Freeman. “Agoraphobia is often the final common pathway in lots of mental health conditions.”

Automated VR not only addresses the problem of patients being too afraid to leave home for in-person treatment but may also help address the shortage of trained mental health care providers.

The intervention is available at pilot implementation sites in the United Kingdom and a few sites in the United States, he said.
 

‘Cool, interesting’

Commenting on the research, Arash Javanbakht, MD, associate professor (clinical scholar), Wayne State University, Detroit, described the study as “cool and interesting.”

However, he said, the findings were not surprising, because exposure therapy has proved effective in treating phobias. Because of the significant lack of access to exposure therapy providers, “the more mechanized, the more automated therapies that can be easily used, the better,” he said.

He noted the VR therapy did not require a high level of training; the study used peer support staff who sat next to those using the technology.

He also liked the fact that the intervention “focused on things that in reality impair a person’s life,” for example, not being able to go to the grocery store.

However, he wondered why the investigators studied VR for patients with psychosis and agoraphobia and not for those with just agoraphobia.

In addition, he noted that the treatment’s efficacy was partly due to having someone next to the participants offering support, which the control group didn’t have.

Dr. Javanbakht has researched augmented therapy (AR) for delivering exposure therapy. This technology, which mixes virtually created objects with reality and allows users to move around their real environment, is newer and more advanced than VR but is more complicated, he said.

He explained that AR is more appropriate for delivering exposure therapy in certain situations.

“The basis of exposure therapy is ‘extinction learning’ – exposing a person to a fear cue over and over again until the fear response is extinguished,” and extinction learning is “context dependent,” said Dr. Javanbakht.

“VR is good when you need to create the whole context and environment, and AR is good when you need to focus on specific objects or cues in the environment,” for example, spiders or snakes, he said.

The study was funded by the National Institute of Health Research. Dr. Freeman is a founder and a non-executive director of Oxford VR, which will commercialize the therapy. He holds equity in and receives personal payments from Oxford VR; holds a contract for his university team to advise Oxford VR on treatment development; and reports grants from the National Institute for Health Research, the Medical Research Council, and the International Foundation. Dr. Javanbakht has a patent for an AR exposure therapy.

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

A novel virtual reality (VR) intervention significantly reduces agoraphobia in patients with psychosis, new research suggests.

The cognitive-behavioral therapy–based treatment was particularly effective for patients with the highest level of avoidance of everyday situations.

Courtesy University of Oxford

“Virtual reality is an inherently therapeutic medium which could be extremely useful in mental health services,” study investigator Daniel Freeman, PhD, DClinPsy, professor of clinical psychology, University of Oxford (England), told this news organization.  “This intervention is coming; the question really is when.”

The study was published online  in The Lancet Psychiatry.
 

Real-world feel

Immersive VR involves interactive three-dimensional computer-generated environments that produce the sensation of being in the real world.

For patients with psychosis, dealing with the real world can be an anxious experience, particularly if they have verbal or auditory hallucinations.

Some may develop agoraphobia and start to avoid places or situations. A virtual environment allows patients to practice dealing with situations that make them anxious or uncomfortable and to learn to reengage in everyday situations.

The study included 346 patients diagnosed with schizophrenia or a related disorder. The mean age of the patients was 37.2 years (67% were men, 85% were White). Most were single and unemployed. All were receiving treatment for psychosis and had difficulty going out because of anxiety.

The researchers randomly assigned 174 participants to an automated VR cognitive therapy intervention (gameChange) plus usual care and 172 to usual care alone. Trial assessors were blinded to group allocation.

The gameChange intervention was delivered in six sessions that were conducted over a 6-week period. Each session involved 30 minutes of VR.

A session begins when participants enter the virtual therapist’s office. They are met by a coach who guides them through the therapy. They can choose from among six VR social situations. These include a cafe, a general practice waiting room, a pub, a bus, opening the front door of their home onto the street, or entering a small local shop.

Each scenario has five levels of difficulty that are based on the number and proximity of people in the social situation and the degree of social interaction. Users can work their way through these various levels.

The virtual sessions took place in patients’ homes in about 50% of cases; the remainder were conducted in the clinic. A mental health worker was in the room during the therapy.

Between virtual sessions, participants were encouraged to apply what they learned in the real world, for example, by spending time in a pub.

Usual care typically included regular visits from a community mental health worker and occasional outpatient appointments with a psychiatrist.
 

Widely applicable?

The primary outcome was the eight-item Oxford Agoraphobic Avoidance Scale (O-AS) questionnaire. This scale assesses distress and avoidance related to performing increasingly difficult everyday tasks.

The researchers assessed patients at baseline, at the conclusion of the 6-week treatment, and at 26 weeks.

Compared with the group that received usual care alone, the VR therapy group demonstrated a significant reduction in both agoraphobic avoidance (O-AS adjusted mean difference, -0.47; 95% confidence interval [CI], –0.88 to –0.06; Cohen’s d, –0.18; P = .026) and distress (–4.33; 95% CI, –7.78 to –0.87; Cohen’s d, –0.26; P = .014) at 6 weeks.

This translates to being able to do about 1.5 more activities on the O-AS, such as going to a shopping center alone, said Dr. Freeman.

Further analyses showed that VR therapy was especially effective for patients with severe agoraphobia. On average, these patients could complete two more O-AS activities at 26 weeks, said Dr. Freeman.

The authors believe the intervention worked by reducing defense behaviors, such as avoiding eye contact and fearful thoughts.

There was no significant difference in occurrence of adverse events between the study groups. These events, which were mild, transient, and did not affect the outcome, included side effects such as claustrophobia when using headsets.

The intervention would likely work for patients with agoraphobia who do not have psychosis, said Dr. Freeman. “Agoraphobia is often the final common pathway in lots of mental health conditions.”

Automated VR not only addresses the problem of patients being too afraid to leave home for in-person treatment but may also help address the shortage of trained mental health care providers.

The intervention is available at pilot implementation sites in the United Kingdom and a few sites in the United States, he said.
 

‘Cool, interesting’

Commenting on the research, Arash Javanbakht, MD, associate professor (clinical scholar), Wayne State University, Detroit, described the study as “cool and interesting.”

However, he said, the findings were not surprising, because exposure therapy has proved effective in treating phobias. Because of the significant lack of access to exposure therapy providers, “the more mechanized, the more automated therapies that can be easily used, the better,” he said.

He noted the VR therapy did not require a high level of training; the study used peer support staff who sat next to those using the technology.

He also liked the fact that the intervention “focused on things that in reality impair a person’s life,” for example, not being able to go to the grocery store.

However, he wondered why the investigators studied VR for patients with psychosis and agoraphobia and not for those with just agoraphobia.

In addition, he noted that the treatment’s efficacy was partly due to having someone next to the participants offering support, which the control group didn’t have.

Dr. Javanbakht has researched augmented therapy (AR) for delivering exposure therapy. This technology, which mixes virtually created objects with reality and allows users to move around their real environment, is newer and more advanced than VR but is more complicated, he said.

He explained that AR is more appropriate for delivering exposure therapy in certain situations.

“The basis of exposure therapy is ‘extinction learning’ – exposing a person to a fear cue over and over again until the fear response is extinguished,” and extinction learning is “context dependent,” said Dr. Javanbakht.

“VR is good when you need to create the whole context and environment, and AR is good when you need to focus on specific objects or cues in the environment,” for example, spiders or snakes, he said.

The study was funded by the National Institute of Health Research. Dr. Freeman is a founder and a non-executive director of Oxford VR, which will commercialize the therapy. He holds equity in and receives personal payments from Oxford VR; holds a contract for his university team to advise Oxford VR on treatment development; and reports grants from the National Institute for Health Research, the Medical Research Council, and the International Foundation. Dr. Javanbakht has a patent for an AR exposure therapy.

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

A novel virtual reality (VR) intervention significantly reduces agoraphobia in patients with psychosis, new research suggests.

The cognitive-behavioral therapy–based treatment was particularly effective for patients with the highest level of avoidance of everyday situations.

Courtesy University of Oxford

“Virtual reality is an inherently therapeutic medium which could be extremely useful in mental health services,” study investigator Daniel Freeman, PhD, DClinPsy, professor of clinical psychology, University of Oxford (England), told this news organization.  “This intervention is coming; the question really is when.”

The study was published online  in The Lancet Psychiatry.
 

Real-world feel

Immersive VR involves interactive three-dimensional computer-generated environments that produce the sensation of being in the real world.

For patients with psychosis, dealing with the real world can be an anxious experience, particularly if they have verbal or auditory hallucinations.

Some may develop agoraphobia and start to avoid places or situations. A virtual environment allows patients to practice dealing with situations that make them anxious or uncomfortable and to learn to reengage in everyday situations.

The study included 346 patients diagnosed with schizophrenia or a related disorder. The mean age of the patients was 37.2 years (67% were men, 85% were White). Most were single and unemployed. All were receiving treatment for psychosis and had difficulty going out because of anxiety.

The researchers randomly assigned 174 participants to an automated VR cognitive therapy intervention (gameChange) plus usual care and 172 to usual care alone. Trial assessors were blinded to group allocation.

The gameChange intervention was delivered in six sessions that were conducted over a 6-week period. Each session involved 30 minutes of VR.

A session begins when participants enter the virtual therapist’s office. They are met by a coach who guides them through the therapy. They can choose from among six VR social situations. These include a cafe, a general practice waiting room, a pub, a bus, opening the front door of their home onto the street, or entering a small local shop.

Each scenario has five levels of difficulty that are based on the number and proximity of people in the social situation and the degree of social interaction. Users can work their way through these various levels.

The virtual sessions took place in patients’ homes in about 50% of cases; the remainder were conducted in the clinic. A mental health worker was in the room during the therapy.

Between virtual sessions, participants were encouraged to apply what they learned in the real world, for example, by spending time in a pub.

Usual care typically included regular visits from a community mental health worker and occasional outpatient appointments with a psychiatrist.
 

Widely applicable?

The primary outcome was the eight-item Oxford Agoraphobic Avoidance Scale (O-AS) questionnaire. This scale assesses distress and avoidance related to performing increasingly difficult everyday tasks.

The researchers assessed patients at baseline, at the conclusion of the 6-week treatment, and at 26 weeks.

Compared with the group that received usual care alone, the VR therapy group demonstrated a significant reduction in both agoraphobic avoidance (O-AS adjusted mean difference, -0.47; 95% confidence interval [CI], –0.88 to –0.06; Cohen’s d, –0.18; P = .026) and distress (–4.33; 95% CI, –7.78 to –0.87; Cohen’s d, –0.26; P = .014) at 6 weeks.

This translates to being able to do about 1.5 more activities on the O-AS, such as going to a shopping center alone, said Dr. Freeman.

Further analyses showed that VR therapy was especially effective for patients with severe agoraphobia. On average, these patients could complete two more O-AS activities at 26 weeks, said Dr. Freeman.

The authors believe the intervention worked by reducing defense behaviors, such as avoiding eye contact and fearful thoughts.

There was no significant difference in occurrence of adverse events between the study groups. These events, which were mild, transient, and did not affect the outcome, included side effects such as claustrophobia when using headsets.

The intervention would likely work for patients with agoraphobia who do not have psychosis, said Dr. Freeman. “Agoraphobia is often the final common pathway in lots of mental health conditions.”

Automated VR not only addresses the problem of patients being too afraid to leave home for in-person treatment but may also help address the shortage of trained mental health care providers.

The intervention is available at pilot implementation sites in the United Kingdom and a few sites in the United States, he said.
 

‘Cool, interesting’

Commenting on the research, Arash Javanbakht, MD, associate professor (clinical scholar), Wayne State University, Detroit, described the study as “cool and interesting.”

However, he said, the findings were not surprising, because exposure therapy has proved effective in treating phobias. Because of the significant lack of access to exposure therapy providers, “the more mechanized, the more automated therapies that can be easily used, the better,” he said.

He noted the VR therapy did not require a high level of training; the study used peer support staff who sat next to those using the technology.

He also liked the fact that the intervention “focused on things that in reality impair a person’s life,” for example, not being able to go to the grocery store.

However, he wondered why the investigators studied VR for patients with psychosis and agoraphobia and not for those with just agoraphobia.

In addition, he noted that the treatment’s efficacy was partly due to having someone next to the participants offering support, which the control group didn’t have.

Dr. Javanbakht has researched augmented therapy (AR) for delivering exposure therapy. This technology, which mixes virtually created objects with reality and allows users to move around their real environment, is newer and more advanced than VR but is more complicated, he said.

He explained that AR is more appropriate for delivering exposure therapy in certain situations.

“The basis of exposure therapy is ‘extinction learning’ – exposing a person to a fear cue over and over again until the fear response is extinguished,” and extinction learning is “context dependent,” said Dr. Javanbakht.

“VR is good when you need to create the whole context and environment, and AR is good when you need to focus on specific objects or cues in the environment,” for example, spiders or snakes, he said.

The study was funded by the National Institute of Health Research. Dr. Freeman is a founder and a non-executive director of Oxford VR, which will commercialize the therapy. He holds equity in and receives personal payments from Oxford VR; holds a contract for his university team to advise Oxford VR on treatment development; and reports grants from the National Institute for Health Research, the Medical Research Council, and the International Foundation. Dr. Javanbakht has a patent for an AR exposure therapy.

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

Stem cell therapy improves motor impairment and is safe and well tolerated in patients with traumatic brain injury (TBI), results from a phase 2 trial indicate. “We proved for the first time that we can affect outcomes in moderately to severely disabled patients with TBI using stem cells,” said study investigator Peter McAllister, MD, cofounder and medical director of the New England Center for Neurology and Headache, Stamford, Conn.

“I think the potential of regenerative medicine was always out there, but we are now getting to the point where we’re living up to that potential,” said Dr. McAllister, associate professor of neurology at Yale University, New Haven, Conn.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

No effective treatment to date

TBI can lead to motor deficits and chronic disability and currently there are no effective drugs to treat these deficits.

Researchers are increasingly focused on using somatic stem cells to restore lost function. Stem cells can differentiate or proliferate into different types of cells and are thought to promote repair and regeneration of tissues or organs damaged due to illness or injury.

The study included 61 patients with TBI with an average age of 34 years (70% were male and 69% were White). The mean time from injury was 8 years and Glasgow Outcome Scale Extended (GOS-E) ranged from 3 to 6.

Forty-six participants were randomly assigned to receive the stem cell therapy and 15 a sham procedure. In the treatment group, there were three different doses of cells (2.5 x 106, 5 x 106, and 10 x 106).

The treatment involved an investigational regenerative cell medicine comprised of bone marrow-derived mesenchymal stem cells (SB623). The allogeneic cells came from a male donor.

For the 20-minute procedure, a neurosurgeon drilled a tiny hole in the skull and, guided by MRI, injected the stem cells into the area of the lesion.

Patients receiving a surgical sham procedure were brought to the operating room, anesthetized, and had a hole drilled into the head over the area of the lesion. However, the surgeon went only halfway through the skull bone.

Participants were instructed to do specific physiotherapy exercises at home every morning and afternoon for the first 6 months of the study.

The primary efficacy endpoint was change in the Fugl-Meyer Motor Scale score (FMMS). This scale is widely used for clinical assessment of motor function, including range of motion, walking, lower limb movement, and dexterity.

At 24 weeks, the change in FMMS score for SB623-treated patients (least square [LS] mean increase 8.3) compared with controls (LS increase 2.3) was significant (P = .04).

“When we looked at all the data at 6 months, the folks who got the stem cells did statistically significantly better than the group that got the sham,” and that improvement began within the first week or two, said Dr. McAllister.
 

‘A real impact’

The treatment had a real impact on people’s lives, he said. “Some who couldn’t move their arm at all were able to put a nut on a bolt or brush their teeth, and some were able to button and unbutton where they couldn’t do that before.”

One teenager who was previously completely aphasic spoke an entire sentence.

The middle dose (5 x 106) had “by far” the best outcome, said Dr. McAllister. It’s not yet known whether the improvements will be permanent, he added.

At 48 weeks, treated patients experienced improvement over controls in secondary endpoints of the Action Research Arm Test (ARAT), which assesses grasp, grip, pinch, and gross movements; Gait Velocity (walking 10 meters); and NeuroQOL, a self-report measure of ability to carry out various activities.

However, although these endpoints were all numerically better in the stem cell groups, none reached statistical significance. This is likely because of the small study size and the fact the control group improved so much, said Dr. McAllister.

The exact mechanism of stem cell therapy is unclear, but researchers believe it “establishes a milieu of growth” for cells in the brain and promotes anti-inflammatory properties, said Dr. McAllister.

By 48 weeks, all study subjects had experienced at least one adverse event, with no differences between groups and no patient withdrawing as a result of adverse events. “There was no safety signal at all related to the stem cells,” said Dr. McAllister.

A larger phase 3 study of SB623 is planned.

The treatment may be useful in other conditions. A study of stroke survivors “just barely missed statistical significance” likely for methodological reasons and an older, sicker population, but the company plans to do another study in patients who were affected by stroke, said Dr. McAllister.

In addition, there may be potential for this approach with brain hemorrhage, Parkinson’s disease, multiple sclerosis, and other brain-related disorders, he said.
 

‘Modern-day holy grail’

Reached for a comment, TBI specialist Frank Conidi, MD, director of the Florida Center for Headache and Sports Neurology, said stem cell therapy is the most promising potential treatment for brain injury. “It’s the modern-day ‘holy grail.’ “

In this study, “to see a modest improvement in gait in the primary outcome is impressive,” he said.

In addition, the fact the study didn’t have any significant or severe adverse outcomes “is promising,” he added.

Studies like this “are going to help to lay the groundwork for future studies and hopefully one day result in a safe, noninvasive treatment” for Parkinson’s disease, Alzheimer’s disease, and disorders that affect the central nervous system such as spinal cord injury, Dr. Conidi said.

This therapy involves an invasive procedure requiring implantation directly into the brain, he noted. “At present, there’s no way to get stem cells to cross the blood-brain barrier.”

In addition, although motor impairment is definitely a component of TBI, it’s not as prevalent as cognitive impairment, said Dr. Conidi.

The study was supported by SanBio Co Ltd. Dr. McAllister and Dr. Conidi have disclosed no relevant financial relationships.

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

Stem cell therapy improves motor impairment and is safe and well tolerated in patients with traumatic brain injury (TBI), results from a phase 2 trial indicate. “We proved for the first time that we can affect outcomes in moderately to severely disabled patients with TBI using stem cells,” said study investigator Peter McAllister, MD, cofounder and medical director of the New England Center for Neurology and Headache, Stamford, Conn.

“I think the potential of regenerative medicine was always out there, but we are now getting to the point where we’re living up to that potential,” said Dr. McAllister, associate professor of neurology at Yale University, New Haven, Conn.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

No effective treatment to date

TBI can lead to motor deficits and chronic disability and currently there are no effective drugs to treat these deficits.

Researchers are increasingly focused on using somatic stem cells to restore lost function. Stem cells can differentiate or proliferate into different types of cells and are thought to promote repair and regeneration of tissues or organs damaged due to illness or injury.

The study included 61 patients with TBI with an average age of 34 years (70% were male and 69% were White). The mean time from injury was 8 years and Glasgow Outcome Scale Extended (GOS-E) ranged from 3 to 6.

Forty-six participants were randomly assigned to receive the stem cell therapy and 15 a sham procedure. In the treatment group, there were three different doses of cells (2.5 x 106, 5 x 106, and 10 x 106).

The treatment involved an investigational regenerative cell medicine comprised of bone marrow-derived mesenchymal stem cells (SB623). The allogeneic cells came from a male donor.

For the 20-minute procedure, a neurosurgeon drilled a tiny hole in the skull and, guided by MRI, injected the stem cells into the area of the lesion.

Patients receiving a surgical sham procedure were brought to the operating room, anesthetized, and had a hole drilled into the head over the area of the lesion. However, the surgeon went only halfway through the skull bone.

Participants were instructed to do specific physiotherapy exercises at home every morning and afternoon for the first 6 months of the study.

The primary efficacy endpoint was change in the Fugl-Meyer Motor Scale score (FMMS). This scale is widely used for clinical assessment of motor function, including range of motion, walking, lower limb movement, and dexterity.

At 24 weeks, the change in FMMS score for SB623-treated patients (least square [LS] mean increase 8.3) compared with controls (LS increase 2.3) was significant (P = .04).

“When we looked at all the data at 6 months, the folks who got the stem cells did statistically significantly better than the group that got the sham,” and that improvement began within the first week or two, said Dr. McAllister.
 

‘A real impact’

The treatment had a real impact on people’s lives, he said. “Some who couldn’t move their arm at all were able to put a nut on a bolt or brush their teeth, and some were able to button and unbutton where they couldn’t do that before.”

One teenager who was previously completely aphasic spoke an entire sentence.

The middle dose (5 x 106) had “by far” the best outcome, said Dr. McAllister. It’s not yet known whether the improvements will be permanent, he added.

At 48 weeks, treated patients experienced improvement over controls in secondary endpoints of the Action Research Arm Test (ARAT), which assesses grasp, grip, pinch, and gross movements; Gait Velocity (walking 10 meters); and NeuroQOL, a self-report measure of ability to carry out various activities.

However, although these endpoints were all numerically better in the stem cell groups, none reached statistical significance. This is likely because of the small study size and the fact the control group improved so much, said Dr. McAllister.

The exact mechanism of stem cell therapy is unclear, but researchers believe it “establishes a milieu of growth” for cells in the brain and promotes anti-inflammatory properties, said Dr. McAllister.

By 48 weeks, all study subjects had experienced at least one adverse event, with no differences between groups and no patient withdrawing as a result of adverse events. “There was no safety signal at all related to the stem cells,” said Dr. McAllister.

A larger phase 3 study of SB623 is planned.

The treatment may be useful in other conditions. A study of stroke survivors “just barely missed statistical significance” likely for methodological reasons and an older, sicker population, but the company plans to do another study in patients who were affected by stroke, said Dr. McAllister.

In addition, there may be potential for this approach with brain hemorrhage, Parkinson’s disease, multiple sclerosis, and other brain-related disorders, he said.
 

‘Modern-day holy grail’

Reached for a comment, TBI specialist Frank Conidi, MD, director of the Florida Center for Headache and Sports Neurology, said stem cell therapy is the most promising potential treatment for brain injury. “It’s the modern-day ‘holy grail.’ “

In this study, “to see a modest improvement in gait in the primary outcome is impressive,” he said.

In addition, the fact the study didn’t have any significant or severe adverse outcomes “is promising,” he added.

Studies like this “are going to help to lay the groundwork for future studies and hopefully one day result in a safe, noninvasive treatment” for Parkinson’s disease, Alzheimer’s disease, and disorders that affect the central nervous system such as spinal cord injury, Dr. Conidi said.

This therapy involves an invasive procedure requiring implantation directly into the brain, he noted. “At present, there’s no way to get stem cells to cross the blood-brain barrier.”

In addition, although motor impairment is definitely a component of TBI, it’s not as prevalent as cognitive impairment, said Dr. Conidi.

The study was supported by SanBio Co Ltd. Dr. McAllister and Dr. Conidi have disclosed no relevant financial relationships.

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

Stem cell therapy improves motor impairment and is safe and well tolerated in patients with traumatic brain injury (TBI), results from a phase 2 trial indicate. “We proved for the first time that we can affect outcomes in moderately to severely disabled patients with TBI using stem cells,” said study investigator Peter McAllister, MD, cofounder and medical director of the New England Center for Neurology and Headache, Stamford, Conn.

“I think the potential of regenerative medicine was always out there, but we are now getting to the point where we’re living up to that potential,” said Dr. McAllister, associate professor of neurology at Yale University, New Haven, Conn.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

No effective treatment to date

TBI can lead to motor deficits and chronic disability and currently there are no effective drugs to treat these deficits.

Researchers are increasingly focused on using somatic stem cells to restore lost function. Stem cells can differentiate or proliferate into different types of cells and are thought to promote repair and regeneration of tissues or organs damaged due to illness or injury.

The study included 61 patients with TBI with an average age of 34 years (70% were male and 69% were White). The mean time from injury was 8 years and Glasgow Outcome Scale Extended (GOS-E) ranged from 3 to 6.

Forty-six participants were randomly assigned to receive the stem cell therapy and 15 a sham procedure. In the treatment group, there were three different doses of cells (2.5 x 106, 5 x 106, and 10 x 106).

The treatment involved an investigational regenerative cell medicine comprised of bone marrow-derived mesenchymal stem cells (SB623). The allogeneic cells came from a male donor.

For the 20-minute procedure, a neurosurgeon drilled a tiny hole in the skull and, guided by MRI, injected the stem cells into the area of the lesion.

Patients receiving a surgical sham procedure were brought to the operating room, anesthetized, and had a hole drilled into the head over the area of the lesion. However, the surgeon went only halfway through the skull bone.

Participants were instructed to do specific physiotherapy exercises at home every morning and afternoon for the first 6 months of the study.

The primary efficacy endpoint was change in the Fugl-Meyer Motor Scale score (FMMS). This scale is widely used for clinical assessment of motor function, including range of motion, walking, lower limb movement, and dexterity.

At 24 weeks, the change in FMMS score for SB623-treated patients (least square [LS] mean increase 8.3) compared with controls (LS increase 2.3) was significant (P = .04).

“When we looked at all the data at 6 months, the folks who got the stem cells did statistically significantly better than the group that got the sham,” and that improvement began within the first week or two, said Dr. McAllister.
 

‘A real impact’

The treatment had a real impact on people’s lives, he said. “Some who couldn’t move their arm at all were able to put a nut on a bolt or brush their teeth, and some were able to button and unbutton where they couldn’t do that before.”

One teenager who was previously completely aphasic spoke an entire sentence.

The middle dose (5 x 106) had “by far” the best outcome, said Dr. McAllister. It’s not yet known whether the improvements will be permanent, he added.

At 48 weeks, treated patients experienced improvement over controls in secondary endpoints of the Action Research Arm Test (ARAT), which assesses grasp, grip, pinch, and gross movements; Gait Velocity (walking 10 meters); and NeuroQOL, a self-report measure of ability to carry out various activities.

However, although these endpoints were all numerically better in the stem cell groups, none reached statistical significance. This is likely because of the small study size and the fact the control group improved so much, said Dr. McAllister.

The exact mechanism of stem cell therapy is unclear, but researchers believe it “establishes a milieu of growth” for cells in the brain and promotes anti-inflammatory properties, said Dr. McAllister.

By 48 weeks, all study subjects had experienced at least one adverse event, with no differences between groups and no patient withdrawing as a result of adverse events. “There was no safety signal at all related to the stem cells,” said Dr. McAllister.

A larger phase 3 study of SB623 is planned.

The treatment may be useful in other conditions. A study of stroke survivors “just barely missed statistical significance” likely for methodological reasons and an older, sicker population, but the company plans to do another study in patients who were affected by stroke, said Dr. McAllister.

In addition, there may be potential for this approach with brain hemorrhage, Parkinson’s disease, multiple sclerosis, and other brain-related disorders, he said.
 

‘Modern-day holy grail’

Reached for a comment, TBI specialist Frank Conidi, MD, director of the Florida Center for Headache and Sports Neurology, said stem cell therapy is the most promising potential treatment for brain injury. “It’s the modern-day ‘holy grail.’ “

In this study, “to see a modest improvement in gait in the primary outcome is impressive,” he said.

In addition, the fact the study didn’t have any significant or severe adverse outcomes “is promising,” he added.

Studies like this “are going to help to lay the groundwork for future studies and hopefully one day result in a safe, noninvasive treatment” for Parkinson’s disease, Alzheimer’s disease, and disorders that affect the central nervous system such as spinal cord injury, Dr. Conidi said.

This therapy involves an invasive procedure requiring implantation directly into the brain, he noted. “At present, there’s no way to get stem cells to cross the blood-brain barrier.”

In addition, although motor impairment is definitely a component of TBI, it’s not as prevalent as cognitive impairment, said Dr. Conidi.

The study was supported by SanBio Co Ltd. Dr. McAllister and Dr. Conidi have disclosed no relevant financial relationships.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

A dose-response relationship exists between number of years playing hockey and risk and severity of chronic traumatic encephalopathy (CTE), new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.

This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”

Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.

The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Football data

CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.

“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”

From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.

The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.

For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.

Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.

Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”

The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
 

Consistent findings

Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.

“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”

Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).

Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.

In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.

The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.

Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.

Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
 

‘Skewed’ population?

Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.

Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.

He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.

“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”

As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.

He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”

The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.

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

A dose-response relationship exists between number of years playing hockey and risk and severity of chronic traumatic encephalopathy (CTE), new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.

This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”

Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.

The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Football data

CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.

“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”

From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.

The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.

For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.

Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.

Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”

The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
 

Consistent findings

Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.

“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”

Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).

Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.

In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.

The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.

Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.

Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
 

‘Skewed’ population?

Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.

Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.

He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.

“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”

As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.

He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”

The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.

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

A dose-response relationship exists between number of years playing hockey and risk and severity of chronic traumatic encephalopathy (CTE), new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.

This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”

Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.

The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Football data

CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.

“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”

From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.

The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.

For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.

Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.

Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”

The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
 

Consistent findings

Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.

“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”

Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).

Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.

In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.

The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.

Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.

Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
 

‘Skewed’ population?

Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.

Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.

He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.

“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”

As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.

He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”

The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.

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

A novel endovascular brain-computer interface is safe and effective, allowing paralyzed patients to use their thoughts to perform daily tasks, results of a small, first-in-human study show.

A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.

“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.

The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.

“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Minimally invasive

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.

“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.

Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.

“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.

Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.

“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”

Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
 

No adverse events

Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.

“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”

The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.

The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.

A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.

Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.

Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.

“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
 

Greater independence

Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.

Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.

Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.

There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.

Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
 

Advancing the field

Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.

Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.

Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.

However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.

“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”

The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.

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

A novel endovascular brain-computer interface is safe and effective, allowing paralyzed patients to use their thoughts to perform daily tasks, results of a small, first-in-human study show.

A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.

“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.

The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.

“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Minimally invasive

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.

“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.

Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.

“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.

Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.

“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”

Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
 

No adverse events

Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.

“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”

The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.

The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.

A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.

Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.

Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.

“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
 

Greater independence

Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.

Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.

Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.

There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.

Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
 

Advancing the field

Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.

Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.

Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.

However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.

“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”

The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.

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

A novel endovascular brain-computer interface is safe and effective, allowing paralyzed patients to use their thoughts to perform daily tasks, results of a small, first-in-human study show.

A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.

“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.

The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.

“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Minimally invasive

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.

“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.

Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.

“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.

Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.

“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”

Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
 

No adverse events

Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.

“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”

The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.

The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.

A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.

Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.

Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.

“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
 

Greater independence

Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.

Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.

Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.

There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.

Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
 

Advancing the field

Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.

Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.

Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.

However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.

“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”

The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.

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

Pregnant women with a history of migraine are at elevated risk for gestational hypertension and preeclampsia, and of delivering their baby preterm, new research suggests. In a large prospective study, researchers also found a link between migraine with aura and increased preeclampsia risk.

Overall, the findings suggest women with a history of migraine may benefit from enhanced monitoring during pregnancy, said coinvestigator Alexandra Purdue-Smithe, PhD, associate epidemiologist at Brigham and Women’s Hospital and instructor of medicine at Harvard Medical School, Boston. “Our results suggest that migraine history may be an important consideration in  obstetric risk assessment,” Dr. Purdue-Smithe added.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Common neurovascular disorder

Migraine is a common neurovascular disorder, affecting about 15% of adults. The condition carries “a pretty remarkable sex bias” as it affects up to three times more women than men, and about a quarter of women in the reproductive age bracket of 18-44 years, Dr. Purdue-Smithe noted.

Despite this, relatively little is known about migraine and pregnancy risks, she said.

What is known is that women with migraine have a higher burden of cardiovascular risk factors such as obesity and chronic hypertension, and these factors can also increase risk for pregnancy complications, she added.

In the study, researchers analyzed data on 30,555 pregnancies in about 19,000 women without a history of cardiovascular disease, type 2 diabetes, or cancer during a 20-year period ending in 2009.

The data came from the Nurses’ Health Study II, a large prospective cohort study established in 1989 when it enrolled women aged 25-42 years. Participants in the ongoing study complete questionnaires every 2 years, reporting information on various health conditions as well as pregnancy and reproductive events.

The investigators estimated associations of physician-diagnosed prepregnancy migraine with preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, and low birth weight (<2,500 grams [5.5 lb]).

About 11% of the women in the study had migraine diagnosed by a physician before pregnancy.

Researchers adjusted for age at pregnancy, race/ethnicity, age at menarche, and prepregnancy chronic hypertension, body mass index, physical activity, smoking status, alcohol intake, history of infertility, parity, oral contraceptive use, and analgesic use.
 

‘A bit surprising’

Results showed that compared with women without a history of migraine, those with such a history had higher risk for preterm delivery (relative risk [RR], 1.17; 95% confidence interval [CI], 1.05-1.30), gestational hypertension (RR, 1.28; 95% CI, 1.11-1.48), and preeclampsia (RR, 1.40; 95% CI, 1.19-1.65).

Prepregnancy migraine was not associated with low birth weight (RR, 0.99; 95% CI, 0.85-1.16) or gestational diabetes (RR, 1.05; 95% CI, .91-1.22).

It was a “bit surprising” that women with migraine had a higher risk for preterm delivery but their babies were not necessarily underweight – although some prior literature had similar findings, said Dr. Purdue-Smithe.

She noted that in her study the association was limited to moderate preterm delivery (gestational age, 32-37 weeks) and not with very preterm births (before 32 weeks).

Researchers also assessed adverse pregnancy outcomes by aura phenotype. “Women with migraine with aura have a higher risk of cardiovascular disease later in life, so we hypothesized that aura might be more strongly associated with adverse pregnancy outcomes with underlying vascular pathology,” Dr. Purdue-Smithe said.

Women with and without aura had elevated risks for preterm delivery and gestational hypertension. Those with aura had a slightly higher risk for preeclampsia (RR, 1.51; 95% CI, 1.22-1.88) than those without aura (RR, 1.29; 95% CI, 1.04-1.61).

As the association between migraine and adverse pregnancy outcomes persisted after adjustment for established cardiovascular and obstetric risk factors, “this suggests there may be subclinical factors that are contributing to elevated risks of these outcomes in women with migraine,” said Dr. Purdue-Smithe.

Such factors could include platelet activation, chronic inflammation, and endothelial dysfunction, she added.

While findings of some previous case-control and retrospective studies suggested a possible link between migraine and adverse pregnancy outcomes, until now few large prospective studies have examined the association.

“Strengths of our study include its prospective design, very large sample size, and more complete adjustment for potential prepregnancy confounders,” Dr. Purdue-Smithe said.
 

Independent risk factor?

In the past, it has been somewhat unclear whether migraine is an independent risk factor for these complications or whether women with migraine just have greater risk factors for adverse pregnancy outcomes.

“Our preliminary findings suggest that migraine is independently associated with these adverse pregnancy outcomes, or at least that’s what it seems,” said Dr. Purdue-Smithe.

The new results could be used by clinicians to “flag” women who may be at risk for complications, she added. “These women may benefit from closer monitoring in pregnancy so that if issues arise, physicians can act quickly.”

She noted that preeclampsia “can come on suddenly and escalate rapidly,” and there are few interventions to treat it besides delivery.

However, low-dose aspirin may be worth investigating. Various health care groups and the U.S. Preventive Services Task Force recommend pregnant women at high risk for preeclampsia take low-dose aspirin (81 mg/d) after 12 weeks’ gestation.

“It would be interesting to see if women with migraine who take aspirin in pregnancy can reduce their risk of preeclampsia, and future research should address this question,” said Dr. Purdue-Smithe.

Additional testing showed that associations with preeclampsia and gestational hypertension did not vary according to age and other obstetrical risks.

The Nurses’ Health Study II did not have information on number and severity of migraine attacks, so the researchers were unable to determine if these factors affect pregnancy outcomes.

“Understanding whether specific migraine features, such as attack frequency, are associated with adverse pregnancy outcomes will be an important area for future research,” said Dr. Purdue-Smithe. She noted prior studies showed the frequency of migraine attacks is related to ischemic stroke and other cardiovascular outcomes.

The authors acknowledged a limitation for the current study: Although migraine history was reported prior to pregnancy, information on migraine aura was collected after most of the pregnancies in the cohort were over. So the findings for migraine aura may have been influenced by participants’ ability to accurately remember their experiences.
 

Collaboration is key

Commenting on the research, Nina Riggins, MD, PhD, director of the Headache and Traumatic Brain Injury Center in the department of neurosciences at the University of California, San Diego, said the study “stands out” because it distinguishes pregnancy complications between those with and without aura among women with migraine. 

Dr. Riggins noted the investigators found the risk of preeclampsia, which on average occurs in about 3%-5% of pregnancies, is higher among women with migraine with aura.  

“The good news is that treatments are available,” she said. “Preconception planning should include this discussion for patients living with migraine.”

However, the study did not compare risks for patients who have frequent migraine attacks versus episodic migraine, Dr. Riggins noted. “We need to learn more about whether any treatments can be safe and effective to decrease risks of complications during pregnancy in this population,” she said.

“I believe, ultimately, what this study reveals is that collaboration among primary care, ob.gyn., maternal-fetal medicine specialists, and neurologists will likely benefit pregnant patients with migraine,” Dr. Riggins said.

The study received funding from the National Institutes of Health. Dr. Purdue-Smithe has disclosed no relevant financial relationships.

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

Pregnant women with a history of migraine are at elevated risk for gestational hypertension and preeclampsia, and of delivering their baby preterm, new research suggests. In a large prospective study, researchers also found a link between migraine with aura and increased preeclampsia risk.

Overall, the findings suggest women with a history of migraine may benefit from enhanced monitoring during pregnancy, said coinvestigator Alexandra Purdue-Smithe, PhD, associate epidemiologist at Brigham and Women’s Hospital and instructor of medicine at Harvard Medical School, Boston. “Our results suggest that migraine history may be an important consideration in  obstetric risk assessment,” Dr. Purdue-Smithe added.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Common neurovascular disorder

Migraine is a common neurovascular disorder, affecting about 15% of adults. The condition carries “a pretty remarkable sex bias” as it affects up to three times more women than men, and about a quarter of women in the reproductive age bracket of 18-44 years, Dr. Purdue-Smithe noted.

Despite this, relatively little is known about migraine and pregnancy risks, she said.

What is known is that women with migraine have a higher burden of cardiovascular risk factors such as obesity and chronic hypertension, and these factors can also increase risk for pregnancy complications, she added.

In the study, researchers analyzed data on 30,555 pregnancies in about 19,000 women without a history of cardiovascular disease, type 2 diabetes, or cancer during a 20-year period ending in 2009.

The data came from the Nurses’ Health Study II, a large prospective cohort study established in 1989 when it enrolled women aged 25-42 years. Participants in the ongoing study complete questionnaires every 2 years, reporting information on various health conditions as well as pregnancy and reproductive events.

The investigators estimated associations of physician-diagnosed prepregnancy migraine with preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, and low birth weight (<2,500 grams [5.5 lb]).

About 11% of the women in the study had migraine diagnosed by a physician before pregnancy.

Researchers adjusted for age at pregnancy, race/ethnicity, age at menarche, and prepregnancy chronic hypertension, body mass index, physical activity, smoking status, alcohol intake, history of infertility, parity, oral contraceptive use, and analgesic use.
 

‘A bit surprising’

Results showed that compared with women without a history of migraine, those with such a history had higher risk for preterm delivery (relative risk [RR], 1.17; 95% confidence interval [CI], 1.05-1.30), gestational hypertension (RR, 1.28; 95% CI, 1.11-1.48), and preeclampsia (RR, 1.40; 95% CI, 1.19-1.65).

Prepregnancy migraine was not associated with low birth weight (RR, 0.99; 95% CI, 0.85-1.16) or gestational diabetes (RR, 1.05; 95% CI, .91-1.22).

It was a “bit surprising” that women with migraine had a higher risk for preterm delivery but their babies were not necessarily underweight – although some prior literature had similar findings, said Dr. Purdue-Smithe.

She noted that in her study the association was limited to moderate preterm delivery (gestational age, 32-37 weeks) and not with very preterm births (before 32 weeks).

Researchers also assessed adverse pregnancy outcomes by aura phenotype. “Women with migraine with aura have a higher risk of cardiovascular disease later in life, so we hypothesized that aura might be more strongly associated with adverse pregnancy outcomes with underlying vascular pathology,” Dr. Purdue-Smithe said.

Women with and without aura had elevated risks for preterm delivery and gestational hypertension. Those with aura had a slightly higher risk for preeclampsia (RR, 1.51; 95% CI, 1.22-1.88) than those without aura (RR, 1.29; 95% CI, 1.04-1.61).

As the association between migraine and adverse pregnancy outcomes persisted after adjustment for established cardiovascular and obstetric risk factors, “this suggests there may be subclinical factors that are contributing to elevated risks of these outcomes in women with migraine,” said Dr. Purdue-Smithe.

Such factors could include platelet activation, chronic inflammation, and endothelial dysfunction, she added.

While findings of some previous case-control and retrospective studies suggested a possible link between migraine and adverse pregnancy outcomes, until now few large prospective studies have examined the association.

“Strengths of our study include its prospective design, very large sample size, and more complete adjustment for potential prepregnancy confounders,” Dr. Purdue-Smithe said.
 

Independent risk factor?

In the past, it has been somewhat unclear whether migraine is an independent risk factor for these complications or whether women with migraine just have greater risk factors for adverse pregnancy outcomes.

“Our preliminary findings suggest that migraine is independently associated with these adverse pregnancy outcomes, or at least that’s what it seems,” said Dr. Purdue-Smithe.

The new results could be used by clinicians to “flag” women who may be at risk for complications, she added. “These women may benefit from closer monitoring in pregnancy so that if issues arise, physicians can act quickly.”

She noted that preeclampsia “can come on suddenly and escalate rapidly,” and there are few interventions to treat it besides delivery.

However, low-dose aspirin may be worth investigating. Various health care groups and the U.S. Preventive Services Task Force recommend pregnant women at high risk for preeclampsia take low-dose aspirin (81 mg/d) after 12 weeks’ gestation.

“It would be interesting to see if women with migraine who take aspirin in pregnancy can reduce their risk of preeclampsia, and future research should address this question,” said Dr. Purdue-Smithe.

Additional testing showed that associations with preeclampsia and gestational hypertension did not vary according to age and other obstetrical risks.

The Nurses’ Health Study II did not have information on number and severity of migraine attacks, so the researchers were unable to determine if these factors affect pregnancy outcomes.

“Understanding whether specific migraine features, such as attack frequency, are associated with adverse pregnancy outcomes will be an important area for future research,” said Dr. Purdue-Smithe. She noted prior studies showed the frequency of migraine attacks is related to ischemic stroke and other cardiovascular outcomes.

The authors acknowledged a limitation for the current study: Although migraine history was reported prior to pregnancy, information on migraine aura was collected after most of the pregnancies in the cohort were over. So the findings for migraine aura may have been influenced by participants’ ability to accurately remember their experiences.
 

Collaboration is key

Commenting on the research, Nina Riggins, MD, PhD, director of the Headache and Traumatic Brain Injury Center in the department of neurosciences at the University of California, San Diego, said the study “stands out” because it distinguishes pregnancy complications between those with and without aura among women with migraine. 

Dr. Riggins noted the investigators found the risk of preeclampsia, which on average occurs in about 3%-5% of pregnancies, is higher among women with migraine with aura.  

“The good news is that treatments are available,” she said. “Preconception planning should include this discussion for patients living with migraine.”

However, the study did not compare risks for patients who have frequent migraine attacks versus episodic migraine, Dr. Riggins noted. “We need to learn more about whether any treatments can be safe and effective to decrease risks of complications during pregnancy in this population,” she said.

“I believe, ultimately, what this study reveals is that collaboration among primary care, ob.gyn., maternal-fetal medicine specialists, and neurologists will likely benefit pregnant patients with migraine,” Dr. Riggins said.

The study received funding from the National Institutes of Health. Dr. Purdue-Smithe has disclosed no relevant financial relationships.

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

Pregnant women with a history of migraine are at elevated risk for gestational hypertension and preeclampsia, and of delivering their baby preterm, new research suggests. In a large prospective study, researchers also found a link between migraine with aura and increased preeclampsia risk.

Overall, the findings suggest women with a history of migraine may benefit from enhanced monitoring during pregnancy, said coinvestigator Alexandra Purdue-Smithe, PhD, associate epidemiologist at Brigham and Women’s Hospital and instructor of medicine at Harvard Medical School, Boston. “Our results suggest that migraine history may be an important consideration in  obstetric risk assessment,” Dr. Purdue-Smithe added.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Common neurovascular disorder

Migraine is a common neurovascular disorder, affecting about 15% of adults. The condition carries “a pretty remarkable sex bias” as it affects up to three times more women than men, and about a quarter of women in the reproductive age bracket of 18-44 years, Dr. Purdue-Smithe noted.

Despite this, relatively little is known about migraine and pregnancy risks, she said.

What is known is that women with migraine have a higher burden of cardiovascular risk factors such as obesity and chronic hypertension, and these factors can also increase risk for pregnancy complications, she added.

In the study, researchers analyzed data on 30,555 pregnancies in about 19,000 women without a history of cardiovascular disease, type 2 diabetes, or cancer during a 20-year period ending in 2009.

The data came from the Nurses’ Health Study II, a large prospective cohort study established in 1989 when it enrolled women aged 25-42 years. Participants in the ongoing study complete questionnaires every 2 years, reporting information on various health conditions as well as pregnancy and reproductive events.

The investigators estimated associations of physician-diagnosed prepregnancy migraine with preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, and low birth weight (<2,500 grams [5.5 lb]).

About 11% of the women in the study had migraine diagnosed by a physician before pregnancy.

Researchers adjusted for age at pregnancy, race/ethnicity, age at menarche, and prepregnancy chronic hypertension, body mass index, physical activity, smoking status, alcohol intake, history of infertility, parity, oral contraceptive use, and analgesic use.
 

‘A bit surprising’

Results showed that compared with women without a history of migraine, those with such a history had higher risk for preterm delivery (relative risk [RR], 1.17; 95% confidence interval [CI], 1.05-1.30), gestational hypertension (RR, 1.28; 95% CI, 1.11-1.48), and preeclampsia (RR, 1.40; 95% CI, 1.19-1.65).

Prepregnancy migraine was not associated with low birth weight (RR, 0.99; 95% CI, 0.85-1.16) or gestational diabetes (RR, 1.05; 95% CI, .91-1.22).

It was a “bit surprising” that women with migraine had a higher risk for preterm delivery but their babies were not necessarily underweight – although some prior literature had similar findings, said Dr. Purdue-Smithe.

She noted that in her study the association was limited to moderate preterm delivery (gestational age, 32-37 weeks) and not with very preterm births (before 32 weeks).

Researchers also assessed adverse pregnancy outcomes by aura phenotype. “Women with migraine with aura have a higher risk of cardiovascular disease later in life, so we hypothesized that aura might be more strongly associated with adverse pregnancy outcomes with underlying vascular pathology,” Dr. Purdue-Smithe said.

Women with and without aura had elevated risks for preterm delivery and gestational hypertension. Those with aura had a slightly higher risk for preeclampsia (RR, 1.51; 95% CI, 1.22-1.88) than those without aura (RR, 1.29; 95% CI, 1.04-1.61).

As the association between migraine and adverse pregnancy outcomes persisted after adjustment for established cardiovascular and obstetric risk factors, “this suggests there may be subclinical factors that are contributing to elevated risks of these outcomes in women with migraine,” said Dr. Purdue-Smithe.

Such factors could include platelet activation, chronic inflammation, and endothelial dysfunction, she added.

While findings of some previous case-control and retrospective studies suggested a possible link between migraine and adverse pregnancy outcomes, until now few large prospective studies have examined the association.

“Strengths of our study include its prospective design, very large sample size, and more complete adjustment for potential prepregnancy confounders,” Dr. Purdue-Smithe said.
 

Independent risk factor?

In the past, it has been somewhat unclear whether migraine is an independent risk factor for these complications or whether women with migraine just have greater risk factors for adverse pregnancy outcomes.

“Our preliminary findings suggest that migraine is independently associated with these adverse pregnancy outcomes, or at least that’s what it seems,” said Dr. Purdue-Smithe.

The new results could be used by clinicians to “flag” women who may be at risk for complications, she added. “These women may benefit from closer monitoring in pregnancy so that if issues arise, physicians can act quickly.”

She noted that preeclampsia “can come on suddenly and escalate rapidly,” and there are few interventions to treat it besides delivery.

However, low-dose aspirin may be worth investigating. Various health care groups and the U.S. Preventive Services Task Force recommend pregnant women at high risk for preeclampsia take low-dose aspirin (81 mg/d) after 12 weeks’ gestation.

“It would be interesting to see if women with migraine who take aspirin in pregnancy can reduce their risk of preeclampsia, and future research should address this question,” said Dr. Purdue-Smithe.

Additional testing showed that associations with preeclampsia and gestational hypertension did not vary according to age and other obstetrical risks.

The Nurses’ Health Study II did not have information on number and severity of migraine attacks, so the researchers were unable to determine if these factors affect pregnancy outcomes.

“Understanding whether specific migraine features, such as attack frequency, are associated with adverse pregnancy outcomes will be an important area for future research,” said Dr. Purdue-Smithe. She noted prior studies showed the frequency of migraine attacks is related to ischemic stroke and other cardiovascular outcomes.

The authors acknowledged a limitation for the current study: Although migraine history was reported prior to pregnancy, information on migraine aura was collected after most of the pregnancies in the cohort were over. So the findings for migraine aura may have been influenced by participants’ ability to accurately remember their experiences.
 

Collaboration is key

Commenting on the research, Nina Riggins, MD, PhD, director of the Headache and Traumatic Brain Injury Center in the department of neurosciences at the University of California, San Diego, said the study “stands out” because it distinguishes pregnancy complications between those with and without aura among women with migraine. 

Dr. Riggins noted the investigators found the risk of preeclampsia, which on average occurs in about 3%-5% of pregnancies, is higher among women with migraine with aura.  

“The good news is that treatments are available,” she said. “Preconception planning should include this discussion for patients living with migraine.”

However, the study did not compare risks for patients who have frequent migraine attacks versus episodic migraine, Dr. Riggins noted. “We need to learn more about whether any treatments can be safe and effective to decrease risks of complications during pregnancy in this population,” she said.

“I believe, ultimately, what this study reveals is that collaboration among primary care, ob.gyn., maternal-fetal medicine specialists, and neurologists will likely benefit pregnant patients with migraine,” Dr. Riggins said.

The study received funding from the National Institutes of Health. Dr. Purdue-Smithe has disclosed no relevant financial relationships.

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