MDedge Neurology

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Dr. Kim

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Dr. Kim

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Dr. Kim

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

Although the prevalence of migraine in the United States has remained stable over the past three decades, migraine-related disability has nearly doubled during that time, a new systematic review showed.

“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.

The study was published online in Headache.

Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.

The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.

Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.

For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.

In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.

Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.

Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.

Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.

Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.

The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.

In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.

It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.

No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

Although the prevalence of migraine in the United States has remained stable over the past three decades, migraine-related disability has nearly doubled during that time, a new systematic review showed.

“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.

The study was published online in Headache.

Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.

The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.

Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.

For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.

In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.

Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.

Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.

Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.

Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.

The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.

In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.

It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.

No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

Although the prevalence of migraine in the United States has remained stable over the past three decades, migraine-related disability has nearly doubled during that time, a new systematic review showed.

“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.

The study was published online in Headache.

Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.

The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.

Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.

For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.

In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.

Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.

Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.

Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.

Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.

The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.

In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.

It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.

No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

I don’t write many checks anymore.

When I started my practice in 2000 I wrote a lot. Paychecks for my staff, my rent, insurance, IRA contributions, federal & state withholding, payments on my EMG machine, pretty much everything.

Checks are old. We’ve been using them in some form for roughly 2000 years.

But the online world has changed a lot of that. Now I write maybe 2-3 a month. I could probably do fewer, but haven’t bothered to set those accounts up that way.

I recently was down to my last few checks, so ordered replacements. The minimum order was 600. As I unpacked the box I realized they’re probably the last ones I’ll need, both because checks are gradually passing by and because there are more days behind in my neurology career than ahead.

The checks are a minor thing, but they do make you think. Certainly we’re in the last generation of people who will ever need to use paper checks. Some phrases like “blank check” will likely be with us long after they’re gone (like “dialing a phone”), but the real deal is heading the same way as 8-Track and VHS tapes.

As my 600 checks dwindle down, realistically, so will my career. There is no rewind button on life. I have no desire to leave medicine right now, but the passage of time changes things.

Does that mean I, like my checks, am also getting obsolete?

I hope not. I’d like to think I still have something to offer. I have 30 years of neurology experience behind me, and try to keep up to date on my field. My patients and staff depend on me to bring my best to the office every day.

I hope to stay that way to the end. I’d rather leave voluntarily, still at the top of my game. Even if I end up leaving a few unused checks behind.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

I don’t write many checks anymore.

When I started my practice in 2000 I wrote a lot. Paychecks for my staff, my rent, insurance, IRA contributions, federal & state withholding, payments on my EMG machine, pretty much everything.

Checks are old. We’ve been using them in some form for roughly 2000 years.

But the online world has changed a lot of that. Now I write maybe 2-3 a month. I could probably do fewer, but haven’t bothered to set those accounts up that way.

I recently was down to my last few checks, so ordered replacements. The minimum order was 600. As I unpacked the box I realized they’re probably the last ones I’ll need, both because checks are gradually passing by and because there are more days behind in my neurology career than ahead.

The checks are a minor thing, but they do make you think. Certainly we’re in the last generation of people who will ever need to use paper checks. Some phrases like “blank check” will likely be with us long after they’re gone (like “dialing a phone”), but the real deal is heading the same way as 8-Track and VHS tapes.

As my 600 checks dwindle down, realistically, so will my career. There is no rewind button on life. I have no desire to leave medicine right now, but the passage of time changes things.

Does that mean I, like my checks, am also getting obsolete?

I hope not. I’d like to think I still have something to offer. I have 30 years of neurology experience behind me, and try to keep up to date on my field. My patients and staff depend on me to bring my best to the office every day.

I hope to stay that way to the end. I’d rather leave voluntarily, still at the top of my game. Even if I end up leaving a few unused checks behind.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

I don’t write many checks anymore.

When I started my practice in 2000 I wrote a lot. Paychecks for my staff, my rent, insurance, IRA contributions, federal & state withholding, payments on my EMG machine, pretty much everything.

Checks are old. We’ve been using them in some form for roughly 2000 years.

But the online world has changed a lot of that. Now I write maybe 2-3 a month. I could probably do fewer, but haven’t bothered to set those accounts up that way.

I recently was down to my last few checks, so ordered replacements. The minimum order was 600. As I unpacked the box I realized they’re probably the last ones I’ll need, both because checks are gradually passing by and because there are more days behind in my neurology career than ahead.

The checks are a minor thing, but they do make you think. Certainly we’re in the last generation of people who will ever need to use paper checks. Some phrases like “blank check” will likely be with us long after they’re gone (like “dialing a phone”), but the real deal is heading the same way as 8-Track and VHS tapes.

As my 600 checks dwindle down, realistically, so will my career. There is no rewind button on life. I have no desire to leave medicine right now, but the passage of time changes things.

Does that mean I, like my checks, am also getting obsolete?

I hope not. I’d like to think I still have something to offer. I have 30 years of neurology experience behind me, and try to keep up to date on my field. My patients and staff depend on me to bring my best to the office every day.

I hope to stay that way to the end. I’d rather leave voluntarily, still at the top of my game. Even if I end up leaving a few unused checks behind.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

BASEL, SWITZERLAND — New findings challenge the practice of rapidly lowering blood pressure (BP) in acute ischemic stroke to allow for speedy thrombolysis.

The observational cluster study showed that patients treated in hospitals that followed the guideline-recommended practice of rapidly reducing BP did no better — and actually showed a trend toward worse outcomes — than those treated in hospitals that did not lower BP, even though this meant fewer patient received thrombolysis. 

“We found insufficient evidence to recommend active blood pressure lowering in patients with ischemic stroke who have blood pressure levels exceeding the guidelines but are otherwise eligible for thrombolytic therapy,” said senior study author Nyika D. Kruyt, MD, PhD, Leiden University Medical Center, the Netherlands. 

“Our results suggest that if the blood pressure is too high for thrombolysis, then it is best to wait and only treat with thrombolysis if the blood pressure drops spontaneously,” Dr. Kruyt said.

The findings were presented at the European Stroke Organisation Conference (ESOC) annual meeting and published online in The Lancet Neurology. 
 

Guidelines Without Evidence?

Owing to concerns about high BP increasing the risk for intracerebral hemorrhage after thrombolysis, the original trials evaluating thrombolysis in stroke set an arbitrary threshold of 185/110 mm Hg, which has been incorporated into stroke guidelines. These trials cautioned against lowering BP rapidly, which is not included in guidelines. 

Most stroke centers therefore tend to rapidly lower BP in patients who have values greater than 185/110 mm Hg and who are otherwise eligible for thrombolysis, investigators noted. Because thrombolysis is more effective the earlier it is administered, there is some urgency to reduce the BP quickly when patients first arrive at the hospital. 

“But there has never been any evidence for the lowering of blood pressure with IV [intravenous] antihypertensives before thrombolysis, and some centers have never adopted this approach because of concerns that a rapid decline in blood pressure may reduce perfusion of the brain at a time when there is already ischemia present,” Dr. Kruyt noted. 

However, if BP is lowered quickly, there is a greater chance that patients will not be able to receive thrombolysis because the 4.5-hour time limit could be exceeded.

For the prospective, observational TRUTH study, researchers compared outcomes in 853 patients treated at 27 stroke centers in the Netherlands with an active BP-lowering strategy vs 199 patients treated at 10 hospitals with no such strategy. 

Baseline characteristics of participants in the two groups were similar. 

Results showed a strong trend toward worse outcomes in participants whose BP was lowered, with an adjusted odds ratio (aOR) for a shift toward a worse 90-day functional outcome on the modified Rankin Scale of 1.27 (95% CI, 0.96-1.68). 

This was despite the fact that many more patients whose BP was reduced received thrombolysis (94% vs 52% of those with no BP lowering) and had shorter times to treatment, with average door-to-needle times of 35 minutes (vs 47 minutes among those with no BP lowering). 

Symptomatic intracranial hemorrhage occurred in 5% of the active BP-lowering group versus 3% of those who did not have their BP lowered (aOR, 1.28; 95% CI, 0.62-2.62).
 

Reconsider Guidelines?

These results are consistent with those from the INTERACT4 trial, which was also presented at the ESOC 2024 meeting. That trial showed a harmful effect of lowering BP in the ambulance in patients with acute ischemic stroke, but a beneficial effect in patients with hemorrhagic stroke.

“I think the guidelines need to be reconsidered after these studies and we should refrain from active blood pressure–lowering in patients with acute ischemic stroke,” Dr. Kruyt said. 

But he acknowledged that not rapidly lowering BP will mean fewer patients will be able to receive thrombolysis within the 4.5-hour treatment window.

Dr. Kruyt estimated that the combination of being eligible for thrombolysis, with the only exclusion criterion being BP greater than 185/110 mm Hg, applies to about 10%-15% of patients. 

“If we have a watch-and-wait policy, then about half of those patients will still get treated with thrombolysis within in the 4.5-hour limit but later than if blood pressure was reduced with IV antihypertensives,” he added. 

Dr. Kruyt noted that there has never been a randomized trial on the practice of BP lowering in order to be able to administer thrombolysis. 

“The 185/110 mm Hg blood pressure level is an arbitrary threshold that was chosen for the original thrombolysis stroke trials,” he said. “I believe we need trials to investigate whether we can give thrombolysis safely to patients with higher blood pressure levels than this, without needing to rapidly reduce the pressure.”
 

Caution Advised

Discussing the TRUTH study at the ESOC meeting, Guillaume Turc, MD, professor of neurology at Sainte-Anne Hospital, Paris, said he thought the findings were “very thought provoking.”

Simona Sacco, MD, professor of neurology at the University of L’Aquila, Italy, said the result was surprising, but she advised caution in acting on this finding. 

“I don’t think this study can change practice or guidelines as it is not a randomized trial. Yes, it can generate a hypothesis, but we need more research before changing clinical practice,” she said. 

In an accompanying editorial, Verónica Olavarría, MD, Clínica Alemana Universidad del Desarrollo, Santiago, Chile, also suggested the trial should be interpreted cautiously because there was “insufficient evidence for a definitive conclusion.”

But Dr. Kruyt noted that even though the TRUTH study was not a randomized trial, the results are in line with those of recent randomized trials such as INTERACT4.

He added that the ENCHANTED trial also showed no benefit of intensive BP management immediately after thrombolysis in mild to moderate stroke and even suggested harm in severe stroke. And other trials (OPTIMAL-BP and ENCHANTED2/MT) have shown worse outcomes with BP lowering in patients with acute ischemic stroke undergoing thrombectomy. 

“All these studies are showing similar signals throughout the whole timeline in acute ischemic stroke. The results are very much in line with each other. I think this strengthens our findings,” Dr. Kruyt said. 

“With this data, I think the guidelines should be revised, and until randomized data become available showing that reducing blood pressure in acute ischemic stroke patients in order for them to receive early thrombolysis is beneficial, then we should refrain from doing so,” he added.

INTERACT4 investigator Craig Anderson, MD, George Institute for Global Health, Sydney, New South Wales, Australia, agreed. 

“The TRUTH study gives the same message as INTERACT4. They are completely in line with each other, both suggesting harm with blood pressure lowering in acute ischemic stroke. These two together are going to rattle the cage around blood pressure control in acute ischemic stroke patients,” Dr. Anderson said. 

The TRUTH study was funded by a grant from Fonds NutsOhra. Dr. Kruyt reported no relevant financial disclosures. Dr. Olavarría reported receiving a grant from Boehringer Ingelheim for the RECCA registry and honoraria from Novo Nordisk.

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — New findings challenge the practice of rapidly lowering blood pressure (BP) in acute ischemic stroke to allow for speedy thrombolysis.

The observational cluster study showed that patients treated in hospitals that followed the guideline-recommended practice of rapidly reducing BP did no better — and actually showed a trend toward worse outcomes — than those treated in hospitals that did not lower BP, even though this meant fewer patient received thrombolysis. 

“We found insufficient evidence to recommend active blood pressure lowering in patients with ischemic stroke who have blood pressure levels exceeding the guidelines but are otherwise eligible for thrombolytic therapy,” said senior study author Nyika D. Kruyt, MD, PhD, Leiden University Medical Center, the Netherlands. 

“Our results suggest that if the blood pressure is too high for thrombolysis, then it is best to wait and only treat with thrombolysis if the blood pressure drops spontaneously,” Dr. Kruyt said.

The findings were presented at the European Stroke Organisation Conference (ESOC) annual meeting and published online in The Lancet Neurology. 
 

Guidelines Without Evidence?

Owing to concerns about high BP increasing the risk for intracerebral hemorrhage after thrombolysis, the original trials evaluating thrombolysis in stroke set an arbitrary threshold of 185/110 mm Hg, which has been incorporated into stroke guidelines. These trials cautioned against lowering BP rapidly, which is not included in guidelines. 

Most stroke centers therefore tend to rapidly lower BP in patients who have values greater than 185/110 mm Hg and who are otherwise eligible for thrombolysis, investigators noted. Because thrombolysis is more effective the earlier it is administered, there is some urgency to reduce the BP quickly when patients first arrive at the hospital. 

“But there has never been any evidence for the lowering of blood pressure with IV [intravenous] antihypertensives before thrombolysis, and some centers have never adopted this approach because of concerns that a rapid decline in blood pressure may reduce perfusion of the brain at a time when there is already ischemia present,” Dr. Kruyt noted. 

However, if BP is lowered quickly, there is a greater chance that patients will not be able to receive thrombolysis because the 4.5-hour time limit could be exceeded.

For the prospective, observational TRUTH study, researchers compared outcomes in 853 patients treated at 27 stroke centers in the Netherlands with an active BP-lowering strategy vs 199 patients treated at 10 hospitals with no such strategy. 

Baseline characteristics of participants in the two groups were similar. 

Results showed a strong trend toward worse outcomes in participants whose BP was lowered, with an adjusted odds ratio (aOR) for a shift toward a worse 90-day functional outcome on the modified Rankin Scale of 1.27 (95% CI, 0.96-1.68). 

This was despite the fact that many more patients whose BP was reduced received thrombolysis (94% vs 52% of those with no BP lowering) and had shorter times to treatment, with average door-to-needle times of 35 minutes (vs 47 minutes among those with no BP lowering). 

Symptomatic intracranial hemorrhage occurred in 5% of the active BP-lowering group versus 3% of those who did not have their BP lowered (aOR, 1.28; 95% CI, 0.62-2.62).
 

Reconsider Guidelines?

These results are consistent with those from the INTERACT4 trial, which was also presented at the ESOC 2024 meeting. That trial showed a harmful effect of lowering BP in the ambulance in patients with acute ischemic stroke, but a beneficial effect in patients with hemorrhagic stroke.

“I think the guidelines need to be reconsidered after these studies and we should refrain from active blood pressure–lowering in patients with acute ischemic stroke,” Dr. Kruyt said. 

But he acknowledged that not rapidly lowering BP will mean fewer patients will be able to receive thrombolysis within the 4.5-hour treatment window.

Dr. Kruyt estimated that the combination of being eligible for thrombolysis, with the only exclusion criterion being BP greater than 185/110 mm Hg, applies to about 10%-15% of patients. 

“If we have a watch-and-wait policy, then about half of those patients will still get treated with thrombolysis within in the 4.5-hour limit but later than if blood pressure was reduced with IV antihypertensives,” he added. 

Dr. Kruyt noted that there has never been a randomized trial on the practice of BP lowering in order to be able to administer thrombolysis. 

“The 185/110 mm Hg blood pressure level is an arbitrary threshold that was chosen for the original thrombolysis stroke trials,” he said. “I believe we need trials to investigate whether we can give thrombolysis safely to patients with higher blood pressure levels than this, without needing to rapidly reduce the pressure.”
 

Caution Advised

Discussing the TRUTH study at the ESOC meeting, Guillaume Turc, MD, professor of neurology at Sainte-Anne Hospital, Paris, said he thought the findings were “very thought provoking.”

Simona Sacco, MD, professor of neurology at the University of L’Aquila, Italy, said the result was surprising, but she advised caution in acting on this finding. 

“I don’t think this study can change practice or guidelines as it is not a randomized trial. Yes, it can generate a hypothesis, but we need more research before changing clinical practice,” she said. 

In an accompanying editorial, Verónica Olavarría, MD, Clínica Alemana Universidad del Desarrollo, Santiago, Chile, also suggested the trial should be interpreted cautiously because there was “insufficient evidence for a definitive conclusion.”

But Dr. Kruyt noted that even though the TRUTH study was not a randomized trial, the results are in line with those of recent randomized trials such as INTERACT4.

He added that the ENCHANTED trial also showed no benefit of intensive BP management immediately after thrombolysis in mild to moderate stroke and even suggested harm in severe stroke. And other trials (OPTIMAL-BP and ENCHANTED2/MT) have shown worse outcomes with BP lowering in patients with acute ischemic stroke undergoing thrombectomy. 

“All these studies are showing similar signals throughout the whole timeline in acute ischemic stroke. The results are very much in line with each other. I think this strengthens our findings,” Dr. Kruyt said. 

“With this data, I think the guidelines should be revised, and until randomized data become available showing that reducing blood pressure in acute ischemic stroke patients in order for them to receive early thrombolysis is beneficial, then we should refrain from doing so,” he added.

INTERACT4 investigator Craig Anderson, MD, George Institute for Global Health, Sydney, New South Wales, Australia, agreed. 

“The TRUTH study gives the same message as INTERACT4. They are completely in line with each other, both suggesting harm with blood pressure lowering in acute ischemic stroke. These two together are going to rattle the cage around blood pressure control in acute ischemic stroke patients,” Dr. Anderson said. 

The TRUTH study was funded by a grant from Fonds NutsOhra. Dr. Kruyt reported no relevant financial disclosures. Dr. Olavarría reported receiving a grant from Boehringer Ingelheim for the RECCA registry and honoraria from Novo Nordisk.

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — New findings challenge the practice of rapidly lowering blood pressure (BP) in acute ischemic stroke to allow for speedy thrombolysis.

The observational cluster study showed that patients treated in hospitals that followed the guideline-recommended practice of rapidly reducing BP did no better — and actually showed a trend toward worse outcomes — than those treated in hospitals that did not lower BP, even though this meant fewer patient received thrombolysis. 

“We found insufficient evidence to recommend active blood pressure lowering in patients with ischemic stroke who have blood pressure levels exceeding the guidelines but are otherwise eligible for thrombolytic therapy,” said senior study author Nyika D. Kruyt, MD, PhD, Leiden University Medical Center, the Netherlands. 

“Our results suggest that if the blood pressure is too high for thrombolysis, then it is best to wait and only treat with thrombolysis if the blood pressure drops spontaneously,” Dr. Kruyt said.

The findings were presented at the European Stroke Organisation Conference (ESOC) annual meeting and published online in The Lancet Neurology. 
 

Guidelines Without Evidence?

Owing to concerns about high BP increasing the risk for intracerebral hemorrhage after thrombolysis, the original trials evaluating thrombolysis in stroke set an arbitrary threshold of 185/110 mm Hg, which has been incorporated into stroke guidelines. These trials cautioned against lowering BP rapidly, which is not included in guidelines. 

Most stroke centers therefore tend to rapidly lower BP in patients who have values greater than 185/110 mm Hg and who are otherwise eligible for thrombolysis, investigators noted. Because thrombolysis is more effective the earlier it is administered, there is some urgency to reduce the BP quickly when patients first arrive at the hospital. 

“But there has never been any evidence for the lowering of blood pressure with IV [intravenous] antihypertensives before thrombolysis, and some centers have never adopted this approach because of concerns that a rapid decline in blood pressure may reduce perfusion of the brain at a time when there is already ischemia present,” Dr. Kruyt noted. 

However, if BP is lowered quickly, there is a greater chance that patients will not be able to receive thrombolysis because the 4.5-hour time limit could be exceeded.

For the prospective, observational TRUTH study, researchers compared outcomes in 853 patients treated at 27 stroke centers in the Netherlands with an active BP-lowering strategy vs 199 patients treated at 10 hospitals with no such strategy. 

Baseline characteristics of participants in the two groups were similar. 

Results showed a strong trend toward worse outcomes in participants whose BP was lowered, with an adjusted odds ratio (aOR) for a shift toward a worse 90-day functional outcome on the modified Rankin Scale of 1.27 (95% CI, 0.96-1.68). 

This was despite the fact that many more patients whose BP was reduced received thrombolysis (94% vs 52% of those with no BP lowering) and had shorter times to treatment, with average door-to-needle times of 35 minutes (vs 47 minutes among those with no BP lowering). 

Symptomatic intracranial hemorrhage occurred in 5% of the active BP-lowering group versus 3% of those who did not have their BP lowered (aOR, 1.28; 95% CI, 0.62-2.62).
 

Reconsider Guidelines?

These results are consistent with those from the INTERACT4 trial, which was also presented at the ESOC 2024 meeting. That trial showed a harmful effect of lowering BP in the ambulance in patients with acute ischemic stroke, but a beneficial effect in patients with hemorrhagic stroke.

“I think the guidelines need to be reconsidered after these studies and we should refrain from active blood pressure–lowering in patients with acute ischemic stroke,” Dr. Kruyt said. 

But he acknowledged that not rapidly lowering BP will mean fewer patients will be able to receive thrombolysis within the 4.5-hour treatment window.

Dr. Kruyt estimated that the combination of being eligible for thrombolysis, with the only exclusion criterion being BP greater than 185/110 mm Hg, applies to about 10%-15% of patients. 

“If we have a watch-and-wait policy, then about half of those patients will still get treated with thrombolysis within in the 4.5-hour limit but later than if blood pressure was reduced with IV antihypertensives,” he added. 

Dr. Kruyt noted that there has never been a randomized trial on the practice of BP lowering in order to be able to administer thrombolysis. 

“The 185/110 mm Hg blood pressure level is an arbitrary threshold that was chosen for the original thrombolysis stroke trials,” he said. “I believe we need trials to investigate whether we can give thrombolysis safely to patients with higher blood pressure levels than this, without needing to rapidly reduce the pressure.”
 

Caution Advised

Discussing the TRUTH study at the ESOC meeting, Guillaume Turc, MD, professor of neurology at Sainte-Anne Hospital, Paris, said he thought the findings were “very thought provoking.”

Simona Sacco, MD, professor of neurology at the University of L’Aquila, Italy, said the result was surprising, but she advised caution in acting on this finding. 

“I don’t think this study can change practice or guidelines as it is not a randomized trial. Yes, it can generate a hypothesis, but we need more research before changing clinical practice,” she said. 

In an accompanying editorial, Verónica Olavarría, MD, Clínica Alemana Universidad del Desarrollo, Santiago, Chile, also suggested the trial should be interpreted cautiously because there was “insufficient evidence for a definitive conclusion.”

But Dr. Kruyt noted that even though the TRUTH study was not a randomized trial, the results are in line with those of recent randomized trials such as INTERACT4.

He added that the ENCHANTED trial also showed no benefit of intensive BP management immediately after thrombolysis in mild to moderate stroke and even suggested harm in severe stroke. And other trials (OPTIMAL-BP and ENCHANTED2/MT) have shown worse outcomes with BP lowering in patients with acute ischemic stroke undergoing thrombectomy. 

“All these studies are showing similar signals throughout the whole timeline in acute ischemic stroke. The results are very much in line with each other. I think this strengthens our findings,” Dr. Kruyt said. 

“With this data, I think the guidelines should be revised, and until randomized data become available showing that reducing blood pressure in acute ischemic stroke patients in order for them to receive early thrombolysis is beneficial, then we should refrain from doing so,” he added.

INTERACT4 investigator Craig Anderson, MD, George Institute for Global Health, Sydney, New South Wales, Australia, agreed. 

“The TRUTH study gives the same message as INTERACT4. They are completely in line with each other, both suggesting harm with blood pressure lowering in acute ischemic stroke. These two together are going to rattle the cage around blood pressure control in acute ischemic stroke patients,” Dr. Anderson said. 

The TRUTH study was funded by a grant from Fonds NutsOhra. Dr. Kruyt reported no relevant financial disclosures. Dr. Olavarría reported receiving a grant from Boehringer Ingelheim for the RECCA registry and honoraria from Novo Nordisk.

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — Minor ischemic stroke patients with intracranial occlusion should not be treated with IV thrombolysis, a new trial has concluded.

Results from the randomized controlled trial TEMPO-2 showed no benefit from treatment with tenecteplase following ischemic stroke. In addition, investigators found a small increased risk for symptomatic intracranial hemorrhage (ICH) and more deaths in the tenecteplase group compared with the control group.

The research suggests that although it makes sense to open up vessels in patients with minor stroke, they didn’t do better with thrombolysis.

“This is not the result we were hoping for, but I think the question of whether to treat these minor stroke patients who are not disabled has now been answered,” said lead investigator Shelagh B. Coutts, MD, University of Calgary, Alberta, Canada.

“After these results, I think we should scan these patients, admit them, give them dual antiplatelet therapy and IV fluids, and watch them like a hawk. If they deteriorate, we can intervene at that point.”

The findings were presented at the European Stroke Organization Conference (ESOC) 2024 annual meeting and published online simultaneously in The Lancet.
 

Very Little Data

Up to half of patients with ischemic stroke initially present with minimal symptoms, which are not disabling, investigators noted. Despite having low scores on the National Institutes of Health Stroke Scale (NIHSS) that typically range from 0 to 5, a third of these patients are dead or disabled at 90-day follow-up if thrombolysis is withheld.

Patients with minor deficits and evidence of an intracranial occlusion are a subpopulation at a high risk for early neurological deterioration, which most often occurs within the first 24 hours after presentation.

However, many physicians have concerns about giving thrombolysis to these patients because of the potential harm from bleeding in the absence of major deficits, and most trials of thrombolysis have excluded patients with minor stroke. That leaves very little high-quality data to guide practice for these patients.

Two previous studies have compared alteplase with antiplatelet agents in minor stroke, but no trial has specifically looked at the subset of patients with minor stroke who have intracranial occlusion. The TEMPO-2 trial was conducted to evaluate the use of tenecteplase in this patient population.

The multicenter, parallel group, open-label study was conducted at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the United Kingdom.

The trial included patients with minor acute ischemic stroke (NIHSS score of 0-5) and intracranial occlusion or focal perfusion abnormality who were within 12 hours from stroke onset.

Patients received IV tenecteplase (0.25 mg/kg) or non-thrombolytic standard of care (control). Most patients in the control group were treated with dual antiplatelet therapy with aspirin and clopidogrel (57%) or aspirin monotherapy (23%).

The trial was stopped early for futility after 886 patients had been enrolled. The median NIHSS score was 2.

The primary outcome — a return to baseline functioning on the modified Rankin Scale score at 90 days — occurred in 75% of the control group and in 72% of the tenecteplase group (risk ratio [RR], 0.96; P = .29).

Although there were significantly more patients with early recanalization and an NIHSS score of 0 at day 5 or discharge after tenecteplase treatment, this did not translate into improved functional outcomes at 90 days.

More patients died in the tenecteplase group compared with the control group (5% vs 1%; adjusted hazard ratio, 3.8; P = .0085).

There were eight (2%) symptomatic ICHs in the tenecteplase group versus two (< 1%) in the control group (RR, 4.2; P = .059).

The ICH rate was not different in patients treated after 4.5 hours versus before 4.5 hours. The subgroup of patients treated at 4.5-12.0 hours showed weaker evidence of better outcomes with thrombolysis than those treated before 4.5 hours, suggesting that the 12-hour window for TEMPO-2 did not explain the absence of benefit seen with tenecteplase.

Patients in the control group did better than expected, which may have been the result of chance, patient selection, or greater use of dual antiplatelet therapy, researchers noted.

Despite higher recanalization rates in the tenecteplase group (48% vs 22%), there was no change in the rate of stroke progression between groups, with an 8% rate of progression seen overall in the study.

Noting that previous studies have shown that patients with minor stroke and intracranial occlusion are at a risk for both progression and disability, the authors suggested that good supportive care may have improved outcomes in both groups.
 

More Trials Needed

Commenting on the study at the ESOC meeting, Urs Fischer, MD, Basel University Hospital, Switzerland, said “What should we do for patients with mild stroke with vessel occlusion has been a huge unanswered question. The TEMPO-2 study did not show a benefit with thrombolysis, and there was a tendency toward an increased risk of ICH. This is an important finding.”

In an accompanying editorial, Simona Sacco, MD, University of L’Aquila, Italy, and Guillaume Turc, MD, Université Paris Cité, France, noted that different minor ischemic stroke populations pose different therapeutic challenges.

Observational data suggest a benefit of endovascular treatment for minor stroke with large vessel occlusion, and dedicated randomized controlled trials in this group are ongoing, they added.

Early dual antiplatelet treatment is now the recommended treatment of minor stroke and should therefore be the active comparator for non-cardioembolic strokes in future trials.

While TEMPO-2 did not prove that tenecteplase is better than the standard of care for the acute treatment of minor stroke, Dr. Sacco and Dr. Turc said the study confirms that tenecteplase is associated with a high rate of recanalization.

“Fast recanalization with intravenous thrombolysis, endovascular treatment, proper patient selection, and combination with dual antiplatelet treatment or early initiation of anticoagulants may translate into tangible clinical benefits for patients with minor ischemic stroke, which should be tested in future studies,” they wrote.

This trial was funded by grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the British Heart Foundation. Boehringer Ingelheim provided tenecteplase for the study. Dr. Coutts reported no conflicts of interest. Dr. Sacco reported receiving grants for research from Novartis and Uriach; consulting fees from Novartis, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca; payment for lectures from Novartis, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca; and support for attending conferences from Lilly, Novartis, Teva, Lundbeck, and Pfizer. She is president elect of the European Stroke Organization and editor-in-chief of Cephalalgia. Dr. Turc reported payment for lectures from Guerbet France, is a member of the scientific advisory board of AI-Stroke, and is the Secretary General of the European Stroke Organisation.

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — Minor ischemic stroke patients with intracranial occlusion should not be treated with IV thrombolysis, a new trial has concluded.

Results from the randomized controlled trial TEMPO-2 showed no benefit from treatment with tenecteplase following ischemic stroke. In addition, investigators found a small increased risk for symptomatic intracranial hemorrhage (ICH) and more deaths in the tenecteplase group compared with the control group.

The research suggests that although it makes sense to open up vessels in patients with minor stroke, they didn’t do better with thrombolysis.

“This is not the result we were hoping for, but I think the question of whether to treat these minor stroke patients who are not disabled has now been answered,” said lead investigator Shelagh B. Coutts, MD, University of Calgary, Alberta, Canada.

“After these results, I think we should scan these patients, admit them, give them dual antiplatelet therapy and IV fluids, and watch them like a hawk. If they deteriorate, we can intervene at that point.”

The findings were presented at the European Stroke Organization Conference (ESOC) 2024 annual meeting and published online simultaneously in The Lancet.
 

Very Little Data

Up to half of patients with ischemic stroke initially present with minimal symptoms, which are not disabling, investigators noted. Despite having low scores on the National Institutes of Health Stroke Scale (NIHSS) that typically range from 0 to 5, a third of these patients are dead or disabled at 90-day follow-up if thrombolysis is withheld.

Patients with minor deficits and evidence of an intracranial occlusion are a subpopulation at a high risk for early neurological deterioration, which most often occurs within the first 24 hours after presentation.

However, many physicians have concerns about giving thrombolysis to these patients because of the potential harm from bleeding in the absence of major deficits, and most trials of thrombolysis have excluded patients with minor stroke. That leaves very little high-quality data to guide practice for these patients.

Two previous studies have compared alteplase with antiplatelet agents in minor stroke, but no trial has specifically looked at the subset of patients with minor stroke who have intracranial occlusion. The TEMPO-2 trial was conducted to evaluate the use of tenecteplase in this patient population.

The multicenter, parallel group, open-label study was conducted at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the United Kingdom.

The trial included patients with minor acute ischemic stroke (NIHSS score of 0-5) and intracranial occlusion or focal perfusion abnormality who were within 12 hours from stroke onset.

Patients received IV tenecteplase (0.25 mg/kg) or non-thrombolytic standard of care (control). Most patients in the control group were treated with dual antiplatelet therapy with aspirin and clopidogrel (57%) or aspirin monotherapy (23%).

The trial was stopped early for futility after 886 patients had been enrolled. The median NIHSS score was 2.

The primary outcome — a return to baseline functioning on the modified Rankin Scale score at 90 days — occurred in 75% of the control group and in 72% of the tenecteplase group (risk ratio [RR], 0.96; P = .29).

Although there were significantly more patients with early recanalization and an NIHSS score of 0 at day 5 or discharge after tenecteplase treatment, this did not translate into improved functional outcomes at 90 days.

More patients died in the tenecteplase group compared with the control group (5% vs 1%; adjusted hazard ratio, 3.8; P = .0085).

There were eight (2%) symptomatic ICHs in the tenecteplase group versus two (< 1%) in the control group (RR, 4.2; P = .059).

The ICH rate was not different in patients treated after 4.5 hours versus before 4.5 hours. The subgroup of patients treated at 4.5-12.0 hours showed weaker evidence of better outcomes with thrombolysis than those treated before 4.5 hours, suggesting that the 12-hour window for TEMPO-2 did not explain the absence of benefit seen with tenecteplase.

Patients in the control group did better than expected, which may have been the result of chance, patient selection, or greater use of dual antiplatelet therapy, researchers noted.

Despite higher recanalization rates in the tenecteplase group (48% vs 22%), there was no change in the rate of stroke progression between groups, with an 8% rate of progression seen overall in the study.

Noting that previous studies have shown that patients with minor stroke and intracranial occlusion are at a risk for both progression and disability, the authors suggested that good supportive care may have improved outcomes in both groups.
 

More Trials Needed

Commenting on the study at the ESOC meeting, Urs Fischer, MD, Basel University Hospital, Switzerland, said “What should we do for patients with mild stroke with vessel occlusion has been a huge unanswered question. The TEMPO-2 study did not show a benefit with thrombolysis, and there was a tendency toward an increased risk of ICH. This is an important finding.”

In an accompanying editorial, Simona Sacco, MD, University of L’Aquila, Italy, and Guillaume Turc, MD, Université Paris Cité, France, noted that different minor ischemic stroke populations pose different therapeutic challenges.

Observational data suggest a benefit of endovascular treatment for minor stroke with large vessel occlusion, and dedicated randomized controlled trials in this group are ongoing, they added.

Early dual antiplatelet treatment is now the recommended treatment of minor stroke and should therefore be the active comparator for non-cardioembolic strokes in future trials.

While TEMPO-2 did not prove that tenecteplase is better than the standard of care for the acute treatment of minor stroke, Dr. Sacco and Dr. Turc said the study confirms that tenecteplase is associated with a high rate of recanalization.

“Fast recanalization with intravenous thrombolysis, endovascular treatment, proper patient selection, and combination with dual antiplatelet treatment or early initiation of anticoagulants may translate into tangible clinical benefits for patients with minor ischemic stroke, which should be tested in future studies,” they wrote.

This trial was funded by grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the British Heart Foundation. Boehringer Ingelheim provided tenecteplase for the study. Dr. Coutts reported no conflicts of interest. Dr. Sacco reported receiving grants for research from Novartis and Uriach; consulting fees from Novartis, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca; payment for lectures from Novartis, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca; and support for attending conferences from Lilly, Novartis, Teva, Lundbeck, and Pfizer. She is president elect of the European Stroke Organization and editor-in-chief of Cephalalgia. Dr. Turc reported payment for lectures from Guerbet France, is a member of the scientific advisory board of AI-Stroke, and is the Secretary General of the European Stroke Organisation.

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — Minor ischemic stroke patients with intracranial occlusion should not be treated with IV thrombolysis, a new trial has concluded.

Results from the randomized controlled trial TEMPO-2 showed no benefit from treatment with tenecteplase following ischemic stroke. In addition, investigators found a small increased risk for symptomatic intracranial hemorrhage (ICH) and more deaths in the tenecteplase group compared with the control group.

The research suggests that although it makes sense to open up vessels in patients with minor stroke, they didn’t do better with thrombolysis.

“This is not the result we were hoping for, but I think the question of whether to treat these minor stroke patients who are not disabled has now been answered,” said lead investigator Shelagh B. Coutts, MD, University of Calgary, Alberta, Canada.

“After these results, I think we should scan these patients, admit them, give them dual antiplatelet therapy and IV fluids, and watch them like a hawk. If they deteriorate, we can intervene at that point.”

The findings were presented at the European Stroke Organization Conference (ESOC) 2024 annual meeting and published online simultaneously in The Lancet.
 

Very Little Data

Up to half of patients with ischemic stroke initially present with minimal symptoms, which are not disabling, investigators noted. Despite having low scores on the National Institutes of Health Stroke Scale (NIHSS) that typically range from 0 to 5, a third of these patients are dead or disabled at 90-day follow-up if thrombolysis is withheld.

Patients with minor deficits and evidence of an intracranial occlusion are a subpopulation at a high risk for early neurological deterioration, which most often occurs within the first 24 hours after presentation.

However, many physicians have concerns about giving thrombolysis to these patients because of the potential harm from bleeding in the absence of major deficits, and most trials of thrombolysis have excluded patients with minor stroke. That leaves very little high-quality data to guide practice for these patients.

Two previous studies have compared alteplase with antiplatelet agents in minor stroke, but no trial has specifically looked at the subset of patients with minor stroke who have intracranial occlusion. The TEMPO-2 trial was conducted to evaluate the use of tenecteplase in this patient population.

The multicenter, parallel group, open-label study was conducted at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the United Kingdom.

The trial included patients with minor acute ischemic stroke (NIHSS score of 0-5) and intracranial occlusion or focal perfusion abnormality who were within 12 hours from stroke onset.

Patients received IV tenecteplase (0.25 mg/kg) or non-thrombolytic standard of care (control). Most patients in the control group were treated with dual antiplatelet therapy with aspirin and clopidogrel (57%) or aspirin monotherapy (23%).

The trial was stopped early for futility after 886 patients had been enrolled. The median NIHSS score was 2.

The primary outcome — a return to baseline functioning on the modified Rankin Scale score at 90 days — occurred in 75% of the control group and in 72% of the tenecteplase group (risk ratio [RR], 0.96; P = .29).

Although there were significantly more patients with early recanalization and an NIHSS score of 0 at day 5 or discharge after tenecteplase treatment, this did not translate into improved functional outcomes at 90 days.

More patients died in the tenecteplase group compared with the control group (5% vs 1%; adjusted hazard ratio, 3.8; P = .0085).

There were eight (2%) symptomatic ICHs in the tenecteplase group versus two (< 1%) in the control group (RR, 4.2; P = .059).

The ICH rate was not different in patients treated after 4.5 hours versus before 4.5 hours. The subgroup of patients treated at 4.5-12.0 hours showed weaker evidence of better outcomes with thrombolysis than those treated before 4.5 hours, suggesting that the 12-hour window for TEMPO-2 did not explain the absence of benefit seen with tenecteplase.

Patients in the control group did better than expected, which may have been the result of chance, patient selection, or greater use of dual antiplatelet therapy, researchers noted.

Despite higher recanalization rates in the tenecteplase group (48% vs 22%), there was no change in the rate of stroke progression between groups, with an 8% rate of progression seen overall in the study.

Noting that previous studies have shown that patients with minor stroke and intracranial occlusion are at a risk for both progression and disability, the authors suggested that good supportive care may have improved outcomes in both groups.
 

More Trials Needed

Commenting on the study at the ESOC meeting, Urs Fischer, MD, Basel University Hospital, Switzerland, said “What should we do for patients with mild stroke with vessel occlusion has been a huge unanswered question. The TEMPO-2 study did not show a benefit with thrombolysis, and there was a tendency toward an increased risk of ICH. This is an important finding.”

In an accompanying editorial, Simona Sacco, MD, University of L’Aquila, Italy, and Guillaume Turc, MD, Université Paris Cité, France, noted that different minor ischemic stroke populations pose different therapeutic challenges.

Observational data suggest a benefit of endovascular treatment for minor stroke with large vessel occlusion, and dedicated randomized controlled trials in this group are ongoing, they added.

Early dual antiplatelet treatment is now the recommended treatment of minor stroke and should therefore be the active comparator for non-cardioembolic strokes in future trials.

While TEMPO-2 did not prove that tenecteplase is better than the standard of care for the acute treatment of minor stroke, Dr. Sacco and Dr. Turc said the study confirms that tenecteplase is associated with a high rate of recanalization.

“Fast recanalization with intravenous thrombolysis, endovascular treatment, proper patient selection, and combination with dual antiplatelet treatment or early initiation of anticoagulants may translate into tangible clinical benefits for patients with minor ischemic stroke, which should be tested in future studies,” they wrote.

This trial was funded by grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the British Heart Foundation. Boehringer Ingelheim provided tenecteplase for the study. Dr. Coutts reported no conflicts of interest. Dr. Sacco reported receiving grants for research from Novartis and Uriach; consulting fees from Novartis, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca; payment for lectures from Novartis, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca; and support for attending conferences from Lilly, Novartis, Teva, Lundbeck, and Pfizer. She is president elect of the European Stroke Organization and editor-in-chief of Cephalalgia. Dr. Turc reported payment for lectures from Guerbet France, is a member of the scientific advisory board of AI-Stroke, and is the Secretary General of the European Stroke Organisation.

A version of this article appeared on Medscape.com.

Incorporating eye-tracking biomarkers into pediatric autism assessments may make identifying the condition easier, according to new findings published in JAMA Network Open.

Researchers created an artificial intelligence–based tool to help primary care clinicians and pediatricians spot potential cases of the neurological condition, according to Brandon Keehn, PhD, associate professor in the Department of Speech, Language, and Hearing Sciences at Purdue University in West Lafayette, Indiana, and an author of the study.

Most primary care clinicians do not receive specialized training in identifying autism, and around a third diagnose the condition with uncertainty, according to Dr. Keehn. The tool helps clinicians by incorporating their diagnosis and self-reported level of certainty with eye-tracking biomarkers. A clinical psychologist also assessed children, either verifying or confuting the earlier results.

The tool produced the same diagnosis as that from a psychologist in 90% of cases. When children were assessed using eye biomarkers alone, the diagnosis was aligned with that of a psychologist 77% of the time.

“This is the first step in demonstrating both that eye-tracking biomarkers are sensitive to autism and whether or not these biomarkers provide extra clinical information for primary care physicians to more accurately diagnose autism,” Dr. Keehn told this news organization.

The study took place between 2019 and 2022 and included 146 children between 14 and 48 months old who were treated at seven primary care practices in Indiana. Dr. Keehn and colleagues asked primary care clinicians to rate their level of certainty in their diagnosis.

During the biomarker test, toddlers watched cartoons while researchers tracked their eye movements. Six biomarkers included in the test were based on previous research linking eye movements to autism, according to Dr. Keehn.

These included whether toddlers looked more at images of people or geometric patterns and the speed and size of pupil dilation when exposed to bright light.

Most toddlers produced a positive result for autism in only one biomarker test. Dr. Keehn said this confirms that children should be tested for a variety of biomarkers because each patient’s condition manifests differently.

Dr. Keehn said his team is still a few steps away from determining how the model would work in a real clinical setting and that they are planning more research with a larger study population.

Alice Kuo, MD, a pediatrician specializing in autism at the University of California, Los Angeles (UCLA), said primary care clinicians should feel comfortable making an autism diagnosis.

“Any tool that helps them to do that can be useful, since wait times for a specialist can take years,” Dr. Kuo, also the director of the Autism Intervention Research Network on Physical Health at UCLA, said.

However, Dr. Kuo said she is concerned about the cases that were falsely identified as positive or negative.

“To be told your kid is autistic when he’s not, or to be told your kid is not when he clinically is, has huge ramifications,” she said.

The study was funded by the National Institute of Mental Health, the Riley Children’s Foundation, and the Indiana Clinical and Translational Sciences Institute. Dr. Keehn reported payments for workshops on the use of the Autism Diagnostic Observation Schedule.

A version of this article appeared on Medscape.com .

Incorporating eye-tracking biomarkers into pediatric autism assessments may make identifying the condition easier, according to new findings published in JAMA Network Open.

Researchers created an artificial intelligence–based tool to help primary care clinicians and pediatricians spot potential cases of the neurological condition, according to Brandon Keehn, PhD, associate professor in the Department of Speech, Language, and Hearing Sciences at Purdue University in West Lafayette, Indiana, and an author of the study.

Most primary care clinicians do not receive specialized training in identifying autism, and around a third diagnose the condition with uncertainty, according to Dr. Keehn. The tool helps clinicians by incorporating their diagnosis and self-reported level of certainty with eye-tracking biomarkers. A clinical psychologist also assessed children, either verifying or confuting the earlier results.

The tool produced the same diagnosis as that from a psychologist in 90% of cases. When children were assessed using eye biomarkers alone, the diagnosis was aligned with that of a psychologist 77% of the time.

“This is the first step in demonstrating both that eye-tracking biomarkers are sensitive to autism and whether or not these biomarkers provide extra clinical information for primary care physicians to more accurately diagnose autism,” Dr. Keehn told this news organization.

The study took place between 2019 and 2022 and included 146 children between 14 and 48 months old who were treated at seven primary care practices in Indiana. Dr. Keehn and colleagues asked primary care clinicians to rate their level of certainty in their diagnosis.

During the biomarker test, toddlers watched cartoons while researchers tracked their eye movements. Six biomarkers included in the test were based on previous research linking eye movements to autism, according to Dr. Keehn.

These included whether toddlers looked more at images of people or geometric patterns and the speed and size of pupil dilation when exposed to bright light.

Most toddlers produced a positive result for autism in only one biomarker test. Dr. Keehn said this confirms that children should be tested for a variety of biomarkers because each patient’s condition manifests differently.

Dr. Keehn said his team is still a few steps away from determining how the model would work in a real clinical setting and that they are planning more research with a larger study population.

Alice Kuo, MD, a pediatrician specializing in autism at the University of California, Los Angeles (UCLA), said primary care clinicians should feel comfortable making an autism diagnosis.

“Any tool that helps them to do that can be useful, since wait times for a specialist can take years,” Dr. Kuo, also the director of the Autism Intervention Research Network on Physical Health at UCLA, said.

However, Dr. Kuo said she is concerned about the cases that were falsely identified as positive or negative.

“To be told your kid is autistic when he’s not, or to be told your kid is not when he clinically is, has huge ramifications,” she said.

The study was funded by the National Institute of Mental Health, the Riley Children’s Foundation, and the Indiana Clinical and Translational Sciences Institute. Dr. Keehn reported payments for workshops on the use of the Autism Diagnostic Observation Schedule.

A version of this article appeared on Medscape.com .

Incorporating eye-tracking biomarkers into pediatric autism assessments may make identifying the condition easier, according to new findings published in JAMA Network Open.

Researchers created an artificial intelligence–based tool to help primary care clinicians and pediatricians spot potential cases of the neurological condition, according to Brandon Keehn, PhD, associate professor in the Department of Speech, Language, and Hearing Sciences at Purdue University in West Lafayette, Indiana, and an author of the study.

Most primary care clinicians do not receive specialized training in identifying autism, and around a third diagnose the condition with uncertainty, according to Dr. Keehn. The tool helps clinicians by incorporating their diagnosis and self-reported level of certainty with eye-tracking biomarkers. A clinical psychologist also assessed children, either verifying or confuting the earlier results.

The tool produced the same diagnosis as that from a psychologist in 90% of cases. When children were assessed using eye biomarkers alone, the diagnosis was aligned with that of a psychologist 77% of the time.

“This is the first step in demonstrating both that eye-tracking biomarkers are sensitive to autism and whether or not these biomarkers provide extra clinical information for primary care physicians to more accurately diagnose autism,” Dr. Keehn told this news organization.

The study took place between 2019 and 2022 and included 146 children between 14 and 48 months old who were treated at seven primary care practices in Indiana. Dr. Keehn and colleagues asked primary care clinicians to rate their level of certainty in their diagnosis.

During the biomarker test, toddlers watched cartoons while researchers tracked their eye movements. Six biomarkers included in the test were based on previous research linking eye movements to autism, according to Dr. Keehn.

These included whether toddlers looked more at images of people or geometric patterns and the speed and size of pupil dilation when exposed to bright light.

Most toddlers produced a positive result for autism in only one biomarker test. Dr. Keehn said this confirms that children should be tested for a variety of biomarkers because each patient’s condition manifests differently.

Dr. Keehn said his team is still a few steps away from determining how the model would work in a real clinical setting and that they are planning more research with a larger study population.

Alice Kuo, MD, a pediatrician specializing in autism at the University of California, Los Angeles (UCLA), said primary care clinicians should feel comfortable making an autism diagnosis.

“Any tool that helps them to do that can be useful, since wait times for a specialist can take years,” Dr. Kuo, also the director of the Autism Intervention Research Network on Physical Health at UCLA, said.

However, Dr. Kuo said she is concerned about the cases that were falsely identified as positive or negative.

“To be told your kid is autistic when he’s not, or to be told your kid is not when he clinically is, has huge ramifications,” she said.

The study was funded by the National Institute of Mental Health, the Riley Children’s Foundation, and the Indiana Clinical and Translational Sciences Institute. Dr. Keehn reported payments for workshops on the use of the Autism Diagnostic Observation Schedule.

A version of this article appeared on Medscape.com .

Consuming highly processed foods may be harmful to the aging brain, independent of other risk factors for adverse neurologic outcomes and adherence to recommended dietary patterns, new research suggests.

Observations from a large cohort of adults followed for more than 10 years suggested that eating more ultraprocessed foods (UPFs) may increase the risk for cognitive decline and stroke, while eating more unprocessed or minimally processed foods may lower the risk.

“The first key takeaway is that the type of food that we eat matters for brain health, but it’s equally important to think about how it’s made and handled when thinking about brain health,” said study investigator W. Taylor Kimberly, MD, PhD, with Massachusetts General Hospital in Boston.

“The second is that it’s not just all a bad news story because while increased consumption of ultra-processed foods is associated with a higher risk of cognitive impairment and stroke, unprocessed foods appear to be protective,” Dr. Kimberly added.

The study was published online on May 22 in Neurology.
 

Food Processing Matters

UPFs are highly manipulated, low in protein and fiber, and packed with added ingredients, including sugar, fat, and salt. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

Unprocessed or minimally processed foods include meats such as simple cuts of beef, pork, and chicken, and vegetables and fruits.

Research has shown associations between high UPF consumption and increased risk for metabolic and neurologic disorders.

As reported previously, in the ELSA-Brasil study, higher intake of UPFs was significantly associated with a faster rate of decline in executive and global cognitive function.

Yet, it’s unclear whether the extent of food processing contributes to the risk of adverse neurologic outcomes independent of dietary patterns.

Dr. Kimberly and colleagues examined the association of food processing levels with the risk for cognitive impairment and stroke in the long-running REGARDS study, a large prospective US cohort of Black and White adults aged 45 years and older.

Food processing levels were defined by the NOVA food classification system, which ranges from unprocessed or minimally processed foods (NOVA1) to UPFs (NOVA4). Dietary patterns were characterized based on food frequency questionnaires.

In the cognitive impairment cohort, 768 of 14,175 adults without evidence of impairment at baseline who underwent follow-up testing developed cognitive impairment.
 

Diet an Opportunity to Protect Brain Health

In multivariable Cox proportional hazards models adjusting for age, sex, high blood pressure, and other factors, a 10% increase in relative intake of UPFs was associated with a 16% higher risk for cognitive impairment (hazard ratio [HR], 1.16). Conversely, a higher intake of unprocessed or minimally processed foods correlated with a 12% lower risk for cognitive impairment (HR, 0.88).

In the stroke cohort, 1108 of 20,243 adults without a history of stroke had a stroke during the follow-up.

In multivariable Cox models, greater intake of UPFs was associated with an 8% increased risk for stroke (HR, 1.08), while greater intake of unprocessed or minimally processed foods correlated with a 9% lower risk for stroke (HR, 0.91).

The effect of UPFs on stroke risk was greater among Black than among White adults (UPF-by-race interaction HR, 1.15).

The associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay diet.

These results “highlight the possibility that we have the capacity to maintain our brain health and prevent poor brain health outcomes by focusing on unprocessed foods in the long term,” Dr. Kimberly said.

He cautioned that this was “an observational study and not an interventional study, so we can’t say with certainty that substituting ultra-processed foods with unprocessed foods will definitively improve brain health,” Dr. Kimberly said. “That’s a clinical trial question that has not been done but our results certainly are provocative.”
 

Consider UPFs in National Guidelines?

The coauthors of an accompanying editorial said the “robust” results from Kimberly and colleagues highlight the “significant role of food processing levels and their relationship with adverse neurologic outcomes, independent of conventional dietary patterns.”

Peipei Gao, MS, with Harvard T.H. Chan School of Public Health, and Zhendong Mei, PhD, with Harvard Medical School, both in Boston, noted that the mechanisms underlying the impact of UPFs on adverse neurologic outcomes “can be attributed not only to their nutritional profiles,” including poor nutrient composition and high glycemic load, “but also to the presence of additives including emulsifiers, colorants, sweeteners, and nitrates/nitrites, which have been associated with disruptions in the gut microbial ecosystem and inflammation.

“Understanding how food processing levels are associated with human health offers a fresh take on the saying ‘you are what you eat,’ ” the editorialists wrote.

This new study, they noted, adds to the evidence by highlighting the link between UPFs and brain health, independent of traditional dietary patterns and “raises questions about whether considerations of UPFs should be included in dietary guidelines, as well as national and global public health policies for improving brain health.”

The editorialists called for large prospective population studies and randomized controlled trials to better understand the link between UPF consumption and brain health. “In addition, mechanistic studies are warranted to identify specific foods, detrimental processes, and additives that play a role in UPFs and their association with neurologic disorders,” they concluded.

Funding for the study was provided by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, National Institutes of Health, and Department of Health and Human Services. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

Consuming highly processed foods may be harmful to the aging brain, independent of other risk factors for adverse neurologic outcomes and adherence to recommended dietary patterns, new research suggests.

Observations from a large cohort of adults followed for more than 10 years suggested that eating more ultraprocessed foods (UPFs) may increase the risk for cognitive decline and stroke, while eating more unprocessed or minimally processed foods may lower the risk.

“The first key takeaway is that the type of food that we eat matters for brain health, but it’s equally important to think about how it’s made and handled when thinking about brain health,” said study investigator W. Taylor Kimberly, MD, PhD, with Massachusetts General Hospital in Boston.

“The second is that it’s not just all a bad news story because while increased consumption of ultra-processed foods is associated with a higher risk of cognitive impairment and stroke, unprocessed foods appear to be protective,” Dr. Kimberly added.

The study was published online on May 22 in Neurology.
 

Food Processing Matters

UPFs are highly manipulated, low in protein and fiber, and packed with added ingredients, including sugar, fat, and salt. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

Unprocessed or minimally processed foods include meats such as simple cuts of beef, pork, and chicken, and vegetables and fruits.

Research has shown associations between high UPF consumption and increased risk for metabolic and neurologic disorders.

As reported previously, in the ELSA-Brasil study, higher intake of UPFs was significantly associated with a faster rate of decline in executive and global cognitive function.

Yet, it’s unclear whether the extent of food processing contributes to the risk of adverse neurologic outcomes independent of dietary patterns.

Dr. Kimberly and colleagues examined the association of food processing levels with the risk for cognitive impairment and stroke in the long-running REGARDS study, a large prospective US cohort of Black and White adults aged 45 years and older.

Food processing levels were defined by the NOVA food classification system, which ranges from unprocessed or minimally processed foods (NOVA1) to UPFs (NOVA4). Dietary patterns were characterized based on food frequency questionnaires.

In the cognitive impairment cohort, 768 of 14,175 adults without evidence of impairment at baseline who underwent follow-up testing developed cognitive impairment.
 

Diet an Opportunity to Protect Brain Health

In multivariable Cox proportional hazards models adjusting for age, sex, high blood pressure, and other factors, a 10% increase in relative intake of UPFs was associated with a 16% higher risk for cognitive impairment (hazard ratio [HR], 1.16). Conversely, a higher intake of unprocessed or minimally processed foods correlated with a 12% lower risk for cognitive impairment (HR, 0.88).

In the stroke cohort, 1108 of 20,243 adults without a history of stroke had a stroke during the follow-up.

In multivariable Cox models, greater intake of UPFs was associated with an 8% increased risk for stroke (HR, 1.08), while greater intake of unprocessed or minimally processed foods correlated with a 9% lower risk for stroke (HR, 0.91).

The effect of UPFs on stroke risk was greater among Black than among White adults (UPF-by-race interaction HR, 1.15).

The associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay diet.

These results “highlight the possibility that we have the capacity to maintain our brain health and prevent poor brain health outcomes by focusing on unprocessed foods in the long term,” Dr. Kimberly said.

He cautioned that this was “an observational study and not an interventional study, so we can’t say with certainty that substituting ultra-processed foods with unprocessed foods will definitively improve brain health,” Dr. Kimberly said. “That’s a clinical trial question that has not been done but our results certainly are provocative.”
 

Consider UPFs in National Guidelines?

The coauthors of an accompanying editorial said the “robust” results from Kimberly and colleagues highlight the “significant role of food processing levels and their relationship with adverse neurologic outcomes, independent of conventional dietary patterns.”

Peipei Gao, MS, with Harvard T.H. Chan School of Public Health, and Zhendong Mei, PhD, with Harvard Medical School, both in Boston, noted that the mechanisms underlying the impact of UPFs on adverse neurologic outcomes “can be attributed not only to their nutritional profiles,” including poor nutrient composition and high glycemic load, “but also to the presence of additives including emulsifiers, colorants, sweeteners, and nitrates/nitrites, which have been associated with disruptions in the gut microbial ecosystem and inflammation.

“Understanding how food processing levels are associated with human health offers a fresh take on the saying ‘you are what you eat,’ ” the editorialists wrote.

This new study, they noted, adds to the evidence by highlighting the link between UPFs and brain health, independent of traditional dietary patterns and “raises questions about whether considerations of UPFs should be included in dietary guidelines, as well as national and global public health policies for improving brain health.”

The editorialists called for large prospective population studies and randomized controlled trials to better understand the link between UPF consumption and brain health. “In addition, mechanistic studies are warranted to identify specific foods, detrimental processes, and additives that play a role in UPFs and their association with neurologic disorders,” they concluded.

Funding for the study was provided by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, National Institutes of Health, and Department of Health and Human Services. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

Consuming highly processed foods may be harmful to the aging brain, independent of other risk factors for adverse neurologic outcomes and adherence to recommended dietary patterns, new research suggests.

Observations from a large cohort of adults followed for more than 10 years suggested that eating more ultraprocessed foods (UPFs) may increase the risk for cognitive decline and stroke, while eating more unprocessed or minimally processed foods may lower the risk.

“The first key takeaway is that the type of food that we eat matters for brain health, but it’s equally important to think about how it’s made and handled when thinking about brain health,” said study investigator W. Taylor Kimberly, MD, PhD, with Massachusetts General Hospital in Boston.

“The second is that it’s not just all a bad news story because while increased consumption of ultra-processed foods is associated with a higher risk of cognitive impairment and stroke, unprocessed foods appear to be protective,” Dr. Kimberly added.

The study was published online on May 22 in Neurology.
 

Food Processing Matters

UPFs are highly manipulated, low in protein and fiber, and packed with added ingredients, including sugar, fat, and salt. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

Unprocessed or minimally processed foods include meats such as simple cuts of beef, pork, and chicken, and vegetables and fruits.

Research has shown associations between high UPF consumption and increased risk for metabolic and neurologic disorders.

As reported previously, in the ELSA-Brasil study, higher intake of UPFs was significantly associated with a faster rate of decline in executive and global cognitive function.

Yet, it’s unclear whether the extent of food processing contributes to the risk of adverse neurologic outcomes independent of dietary patterns.

Dr. Kimberly and colleagues examined the association of food processing levels with the risk for cognitive impairment and stroke in the long-running REGARDS study, a large prospective US cohort of Black and White adults aged 45 years and older.

Food processing levels were defined by the NOVA food classification system, which ranges from unprocessed or minimally processed foods (NOVA1) to UPFs (NOVA4). Dietary patterns were characterized based on food frequency questionnaires.

In the cognitive impairment cohort, 768 of 14,175 adults without evidence of impairment at baseline who underwent follow-up testing developed cognitive impairment.
 

Diet an Opportunity to Protect Brain Health

In multivariable Cox proportional hazards models adjusting for age, sex, high blood pressure, and other factors, a 10% increase in relative intake of UPFs was associated with a 16% higher risk for cognitive impairment (hazard ratio [HR], 1.16). Conversely, a higher intake of unprocessed or minimally processed foods correlated with a 12% lower risk for cognitive impairment (HR, 0.88).

In the stroke cohort, 1108 of 20,243 adults without a history of stroke had a stroke during the follow-up.

In multivariable Cox models, greater intake of UPFs was associated with an 8% increased risk for stroke (HR, 1.08), while greater intake of unprocessed or minimally processed foods correlated with a 9% lower risk for stroke (HR, 0.91).

The effect of UPFs on stroke risk was greater among Black than among White adults (UPF-by-race interaction HR, 1.15).

The associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay diet.

These results “highlight the possibility that we have the capacity to maintain our brain health and prevent poor brain health outcomes by focusing on unprocessed foods in the long term,” Dr. Kimberly said.

He cautioned that this was “an observational study and not an interventional study, so we can’t say with certainty that substituting ultra-processed foods with unprocessed foods will definitively improve brain health,” Dr. Kimberly said. “That’s a clinical trial question that has not been done but our results certainly are provocative.”
 

Consider UPFs in National Guidelines?

The coauthors of an accompanying editorial said the “robust” results from Kimberly and colleagues highlight the “significant role of food processing levels and their relationship with adverse neurologic outcomes, independent of conventional dietary patterns.”

Peipei Gao, MS, with Harvard T.H. Chan School of Public Health, and Zhendong Mei, PhD, with Harvard Medical School, both in Boston, noted that the mechanisms underlying the impact of UPFs on adverse neurologic outcomes “can be attributed not only to their nutritional profiles,” including poor nutrient composition and high glycemic load, “but also to the presence of additives including emulsifiers, colorants, sweeteners, and nitrates/nitrites, which have been associated with disruptions in the gut microbial ecosystem and inflammation.

“Understanding how food processing levels are associated with human health offers a fresh take on the saying ‘you are what you eat,’ ” the editorialists wrote.

This new study, they noted, adds to the evidence by highlighting the link between UPFs and brain health, independent of traditional dietary patterns and “raises questions about whether considerations of UPFs should be included in dietary guidelines, as well as national and global public health policies for improving brain health.”

The editorialists called for large prospective population studies and randomized controlled trials to better understand the link between UPF consumption and brain health. “In addition, mechanistic studies are warranted to identify specific foods, detrimental processes, and additives that play a role in UPFs and their association with neurologic disorders,” they concluded.

Funding for the study was provided by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, National Institutes of Health, and Department of Health and Human Services. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.