Neurology

Neurologists across the country are reporting a drop in the number of acute stroke patients seeking emergency care during the COVID-19 pandemic – suggesting that some patients may be intentionally staying home rather than risking coronavirus exposure at hospital emergency departments (EDs).

Stroke specialists in New Orleans, Chicago, Seattle, and elsewhere told Medscape Medical News they are seeing a precipitous drop in the number of acute strokes at their institutions – and not just in the number of milder cases. Doctors on Twitter are sharing similar reports and are using social media to highlight this issue.

Gabriel Vidal, MD, a vascular and interventional neurologist at the Ochsner Medical Center, New Orleans, Louisiana, said there are “definitely” fewer patients with stroke and transient ischemic attack (TIA) seeking care at his facility and others throughout the New Orleans area, which has been hard hit by COVID-19.

“Even in Louisiana, we have a very large 53-hospital telestroke network, and the number of consults has diminished greatly,” Vidal added.

In Chicago, emergency medical service activations for patients with suspected strokes are down about 30%, Shyam Prabhakaran, MD, professor and chair of neurology at the University of Chicago Biological Sciences, Illinois, told Medscape Medical News.

“It appears to be that mild stroke and TIA patients may be more likely to stay at home and seek alternative care rather than come to the ED,” Prabhakaran said. However, “the severe strokes may be less affected and continue to come to emergency departments.”

“Getting the Word Out”

That may not be the whole story in Seattle, Washington, where a stroke specialist at Harborview Medical Center reported a drop in patients across the stroke-severity spectrum.

Some patients with milder strokes no longer come to Harborview for a comprehensive evaluation and workup, but that is only “a partial explanation,” said David Tirschwell, MD, medical director of comprehensive stroke care at the University of Washington (UW) Medicine Stroke Center at Harborview and a professor of neurology at UW.

“The thrombectomies are down also,” he added. “It’s hard to have great numbers in real time, but it’s probably safe to say it’s at least a 50% reduction in the number of admissions.”

As a stroke referral center, his institution is seeing fewer local cases and referrals from outside hospitals. “I think both of those sources for admissions of stroke cases are down,” Tirschwell said.

Recognizing the seriousness of forgoing essential care for acute stroke, neurologists, institutions, and medical groups are taking to social media to potentially save lives.

“Across our @FLStrokeReg we are seeing less patients with #stroke symptoms coming to our hospitals. We need to get the word out that our teams are working hard to safely provide care when needed during #COVID19,” tweeted Ralph Sacco, MD, chief and professor of neurology, University of Miami Miller School of Medicine in South Florida.

Although Florida Stroke Registry data are not publicly available, anecdotal reports suggest that stroke admissions are down among many hospitals, Sacco told Medscape Medical News.

Furthermore, this is not a phenomenon only in the United States. “This has also been reported in other nations hit by COVID-19,” he said.

China is a prime example. There, many stroke centers have shown reduced functioning “because of fear of in-hospital cross infection and lack of experienced stroke care experts,” Jing Zhao, MD, PhD, and colleagues write in an editorial published online March 31 in Stroke.

Preliminary data show that “thrombectomies in Shanghai decreased by 50% in the first month after the Spring Festival compared with the same period in 2019,” write the editorialists, who are from Kings College London and the University of Pennsylvania in Philadelphia.

“Although the control of the COVID-19 is very important, at the same time, the management of stroke must not be neglected,” they add.

“Over 9000 new stroke cases occur each day in China alone. It cannot be right that treatment for one potentially curable disease is euthanized at the expense of another.”
 

Fear Factor?

The reasons individuals who may have experienced a stroke are avoiding emergency care is unclear at the moment. “I’m not really sure anyone really understands why, quite honestly,” Tirschwell said.

Until survey data or other data emerge, many experts are assuming that fear of COVID-19 is trumping other medical concerns, including emergency treatment of stroke.

“We believe this could represent patients being fearful to come to medical facilities with stroke-like symptoms, given the COVID-19 pandemic,” said Sacco, who is also incoming editor-in-chief of Stroke.

The BBC has been getting the word out in the United Kingdom via social media, with a tweet to “Dial 999 for stroke emergencies despite coronavirus.”

The World Stroke Campaign is also using Twitter to emphasize the need for urgent stroke care when appropriate:

“Don’t let concerns about COVID19 prevent you from seeking emergency treatment for stroke. If you spot the signs of stroke act FAST. Get emergency medical assistance,” the group urged in a tweet.

Don’t Hesitate

The American Heart Association (AHA) has addressed this troubling trend as well.

“People with serious symptoms shouldn’t ignore them,” Sarah Perlman, MD, associate professor of emergency medicine at the University of Colorado School of Medicine, Denver, states in an article on the AHA website.

Perlman added that some individuals who have signs of stroke and heart disease may hesitate to seek care because of fear that they are adding to an overburdened healthcare staff and system. However, she dismissed those concerns outright.

“If you’re experiencing warning signs of a heart attack or stroke, call 911,” she said. “Clearly, if there’s an emergency, we are available and capable and eager to take care of you.”

This article first appeared on Medscape.com.

Neurologists across the country are reporting a drop in the number of acute stroke patients seeking emergency care during the COVID-19 pandemic – suggesting that some patients may be intentionally staying home rather than risking coronavirus exposure at hospital emergency departments (EDs).

Stroke specialists in New Orleans, Chicago, Seattle, and elsewhere told Medscape Medical News they are seeing a precipitous drop in the number of acute strokes at their institutions – and not just in the number of milder cases. Doctors on Twitter are sharing similar reports and are using social media to highlight this issue.

Gabriel Vidal, MD, a vascular and interventional neurologist at the Ochsner Medical Center, New Orleans, Louisiana, said there are “definitely” fewer patients with stroke and transient ischemic attack (TIA) seeking care at his facility and others throughout the New Orleans area, which has been hard hit by COVID-19.

“Even in Louisiana, we have a very large 53-hospital telestroke network, and the number of consults has diminished greatly,” Vidal added.

In Chicago, emergency medical service activations for patients with suspected strokes are down about 30%, Shyam Prabhakaran, MD, professor and chair of neurology at the University of Chicago Biological Sciences, Illinois, told Medscape Medical News.

“It appears to be that mild stroke and TIA patients may be more likely to stay at home and seek alternative care rather than come to the ED,” Prabhakaran said. However, “the severe strokes may be less affected and continue to come to emergency departments.”

“Getting the Word Out”

That may not be the whole story in Seattle, Washington, where a stroke specialist at Harborview Medical Center reported a drop in patients across the stroke-severity spectrum.

Some patients with milder strokes no longer come to Harborview for a comprehensive evaluation and workup, but that is only “a partial explanation,” said David Tirschwell, MD, medical director of comprehensive stroke care at the University of Washington (UW) Medicine Stroke Center at Harborview and a professor of neurology at UW.

“The thrombectomies are down also,” he added. “It’s hard to have great numbers in real time, but it’s probably safe to say it’s at least a 50% reduction in the number of admissions.”

As a stroke referral center, his institution is seeing fewer local cases and referrals from outside hospitals. “I think both of those sources for admissions of stroke cases are down,” Tirschwell said.

Recognizing the seriousness of forgoing essential care for acute stroke, neurologists, institutions, and medical groups are taking to social media to potentially save lives.

“Across our @FLStrokeReg we are seeing less patients with #stroke symptoms coming to our hospitals. We need to get the word out that our teams are working hard to safely provide care when needed during #COVID19,” tweeted Ralph Sacco, MD, chief and professor of neurology, University of Miami Miller School of Medicine in South Florida.

Although Florida Stroke Registry data are not publicly available, anecdotal reports suggest that stroke admissions are down among many hospitals, Sacco told Medscape Medical News.

Furthermore, this is not a phenomenon only in the United States. “This has also been reported in other nations hit by COVID-19,” he said.

China is a prime example. There, many stroke centers have shown reduced functioning “because of fear of in-hospital cross infection and lack of experienced stroke care experts,” Jing Zhao, MD, PhD, and colleagues write in an editorial published online March 31 in Stroke.

Preliminary data show that “thrombectomies in Shanghai decreased by 50% in the first month after the Spring Festival compared with the same period in 2019,” write the editorialists, who are from Kings College London and the University of Pennsylvania in Philadelphia.

“Although the control of the COVID-19 is very important, at the same time, the management of stroke must not be neglected,” they add.

“Over 9000 new stroke cases occur each day in China alone. It cannot be right that treatment for one potentially curable disease is euthanized at the expense of another.”
 

Fear Factor?

The reasons individuals who may have experienced a stroke are avoiding emergency care is unclear at the moment. “I’m not really sure anyone really understands why, quite honestly,” Tirschwell said.

Until survey data or other data emerge, many experts are assuming that fear of COVID-19 is trumping other medical concerns, including emergency treatment of stroke.

“We believe this could represent patients being fearful to come to medical facilities with stroke-like symptoms, given the COVID-19 pandemic,” said Sacco, who is also incoming editor-in-chief of Stroke.

The BBC has been getting the word out in the United Kingdom via social media, with a tweet to “Dial 999 for stroke emergencies despite coronavirus.”

The World Stroke Campaign is also using Twitter to emphasize the need for urgent stroke care when appropriate:

“Don’t let concerns about COVID19 prevent you from seeking emergency treatment for stroke. If you spot the signs of stroke act FAST. Get emergency medical assistance,” the group urged in a tweet.

Don’t Hesitate

The American Heart Association (AHA) has addressed this troubling trend as well.

“People with serious symptoms shouldn’t ignore them,” Sarah Perlman, MD, associate professor of emergency medicine at the University of Colorado School of Medicine, Denver, states in an article on the AHA website.

Perlman added that some individuals who have signs of stroke and heart disease may hesitate to seek care because of fear that they are adding to an overburdened healthcare staff and system. However, she dismissed those concerns outright.

“If you’re experiencing warning signs of a heart attack or stroke, call 911,” she said. “Clearly, if there’s an emergency, we are available and capable and eager to take care of you.”

This article first appeared on Medscape.com.

Neurologists across the country are reporting a drop in the number of acute stroke patients seeking emergency care during the COVID-19 pandemic – suggesting that some patients may be intentionally staying home rather than risking coronavirus exposure at hospital emergency departments (EDs).

Stroke specialists in New Orleans, Chicago, Seattle, and elsewhere told Medscape Medical News they are seeing a precipitous drop in the number of acute strokes at their institutions – and not just in the number of milder cases. Doctors on Twitter are sharing similar reports and are using social media to highlight this issue.

Gabriel Vidal, MD, a vascular and interventional neurologist at the Ochsner Medical Center, New Orleans, Louisiana, said there are “definitely” fewer patients with stroke and transient ischemic attack (TIA) seeking care at his facility and others throughout the New Orleans area, which has been hard hit by COVID-19.

“Even in Louisiana, we have a very large 53-hospital telestroke network, and the number of consults has diminished greatly,” Vidal added.

In Chicago, emergency medical service activations for patients with suspected strokes are down about 30%, Shyam Prabhakaran, MD, professor and chair of neurology at the University of Chicago Biological Sciences, Illinois, told Medscape Medical News.

“It appears to be that mild stroke and TIA patients may be more likely to stay at home and seek alternative care rather than come to the ED,” Prabhakaran said. However, “the severe strokes may be less affected and continue to come to emergency departments.”

“Getting the Word Out”

That may not be the whole story in Seattle, Washington, where a stroke specialist at Harborview Medical Center reported a drop in patients across the stroke-severity spectrum.

Some patients with milder strokes no longer come to Harborview for a comprehensive evaluation and workup, but that is only “a partial explanation,” said David Tirschwell, MD, medical director of comprehensive stroke care at the University of Washington (UW) Medicine Stroke Center at Harborview and a professor of neurology at UW.

“The thrombectomies are down also,” he added. “It’s hard to have great numbers in real time, but it’s probably safe to say it’s at least a 50% reduction in the number of admissions.”

As a stroke referral center, his institution is seeing fewer local cases and referrals from outside hospitals. “I think both of those sources for admissions of stroke cases are down,” Tirschwell said.

Recognizing the seriousness of forgoing essential care for acute stroke, neurologists, institutions, and medical groups are taking to social media to potentially save lives.

“Across our @FLStrokeReg we are seeing less patients with #stroke symptoms coming to our hospitals. We need to get the word out that our teams are working hard to safely provide care when needed during #COVID19,” tweeted Ralph Sacco, MD, chief and professor of neurology, University of Miami Miller School of Medicine in South Florida.

Although Florida Stroke Registry data are not publicly available, anecdotal reports suggest that stroke admissions are down among many hospitals, Sacco told Medscape Medical News.

Furthermore, this is not a phenomenon only in the United States. “This has also been reported in other nations hit by COVID-19,” he said.

China is a prime example. There, many stroke centers have shown reduced functioning “because of fear of in-hospital cross infection and lack of experienced stroke care experts,” Jing Zhao, MD, PhD, and colleagues write in an editorial published online March 31 in Stroke.

Preliminary data show that “thrombectomies in Shanghai decreased by 50% in the first month after the Spring Festival compared with the same period in 2019,” write the editorialists, who are from Kings College London and the University of Pennsylvania in Philadelphia.

“Although the control of the COVID-19 is very important, at the same time, the management of stroke must not be neglected,” they add.

“Over 9000 new stroke cases occur each day in China alone. It cannot be right that treatment for one potentially curable disease is euthanized at the expense of another.”
 

Fear Factor?

The reasons individuals who may have experienced a stroke are avoiding emergency care is unclear at the moment. “I’m not really sure anyone really understands why, quite honestly,” Tirschwell said.

Until survey data or other data emerge, many experts are assuming that fear of COVID-19 is trumping other medical concerns, including emergency treatment of stroke.

“We believe this could represent patients being fearful to come to medical facilities with stroke-like symptoms, given the COVID-19 pandemic,” said Sacco, who is also incoming editor-in-chief of Stroke.

The BBC has been getting the word out in the United Kingdom via social media, with a tweet to “Dial 999 for stroke emergencies despite coronavirus.”

The World Stroke Campaign is also using Twitter to emphasize the need for urgent stroke care when appropriate:

“Don’t let concerns about COVID19 prevent you from seeking emergency treatment for stroke. If you spot the signs of stroke act FAST. Get emergency medical assistance,” the group urged in a tweet.

Don’t Hesitate

The American Heart Association (AHA) has addressed this troubling trend as well.

“People with serious symptoms shouldn’t ignore them,” Sarah Perlman, MD, associate professor of emergency medicine at the University of Colorado School of Medicine, Denver, states in an article on the AHA website.

Perlman added that some individuals who have signs of stroke and heart disease may hesitate to seek care because of fear that they are adding to an overburdened healthcare staff and system. However, she dismissed those concerns outright.

“If you’re experiencing warning signs of a heart attack or stroke, call 911,” she said. “Clearly, if there’s an emergency, we are available and capable and eager to take care of you.”

This article first appeared on Medscape.com.

STOWE, VT – The preventive treatment of migraine has the potential to change patients’ lives and modify the trajectory of the disease, said Rebecca Burch, MD, staff attending neurologist at Brigham and Women’s Hospital in Boston. Clinical observation suggests that preventive treatment provides benefits for appropriately selected migraineurs, although few data confirm a modifying effect on disease course, she said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England. In her overview, Dr. Burch discussed when preventive treatment is appropriate, which patients are candidates for preventive therapy, and what the levels of evidence are for the preventive therapies.

Identifying candidates for preventive treatment

Migraine is the second most disabling condition worldwide and imposes a large social and economic burden, said Dr. Burch. Preventive therapy reduces the disability associated with migraine. It reduces headache frequency and, thus, the risk that episodic migraine will transform into chronic migraine. By reducing the number of headache days, preventive treatment also may reduce the overuse of acute medication, which is a risk factor for migraine chronification.

Neurologists can consider preventive therapy for migraineurs with frequent headaches, but the term “frequent” is not clearly defined. Common definitions include one headache per week and two headaches per month with significant disability. These definitions are based on expert consensus and do not have strong evidential support, said Dr. Burch. Preventive therapy also may be appropriate for migraineurs who overuse acute medication or who have failed acute medications. Special cases, such as patients with exceptional anxiety or disability, may also call for preventive treatment, said Dr. Burch.

Data suggest that preventive treatment for migraine is underused. The American Migraine Prevalence and Prevention study of 2007 found that half of patients who should be offered preventive treatment are currently receiving it. In 2016, the Chronic Migraine Epidemiology and Outcomes study found that 4.5% of chronic migraineurs take both acute and preventive treatment.

Other data published in Cephalalgia in 2015 indicate that adherence to migraine preventive treatment is approximately 20%. About 45% of patients discontinue medication because of side effects, and 45% cite lack of efficacy as their reason for discontinuation. Patients also mentioned cost, interactions with other medications, and the inconvenience of daily medication as other reasons for discontinuation.

Neurologists can take several steps to increase adherence to preventive treatment, said Dr. Burch. First, neurologists should confirm that patients want preventive medication. A clear discussion of the goals of preventive treatment is helpful as well. Furthermore, neurologists should explain that they are offering patients a trial, said Dr. Burch. The medication can be titrated slowly from a low dose to minimize side effects. Patients can be reassured that ineffective medications will be stopped. Neurologists can emphasize that their relationship with the patient is a partnership and that the treatment strategy will be improved over time.
 

Examining the evidence on treatments’ efficacy

Many drug classes, such as antiepileptics, antidepressants, beta blockers, neurotoxins, and calcitonin gene-related peptide (CGRP) antibodies, include therapies that are used as preventive treatments for migraine. When selecting a medication, a neurologist should start with one that is supported by Level A or Level B evidence, said Dr. Burch. Medications with Level A evidence include divalproex, topiramate, metoprolol, propranolol, erenumab, galcanezumab, fremanezumab, eptinezumab, and onabotulinumtoxinA. Medications with Level B evidence include amitriptyline, venlafaxine, memantine, lisinopril, and candesartan. Neurologists sometimes prescribe gabapentin and verapamil, although the evidence for them is Level U. Duloxetine, nortriptyline, and pregabalin also are used, but the evidence for them has not been evaluated. “We need more evidence in these areas,” said Dr. Burch.

Neurologists should consider access (e.g., cost and insurance coverage), efficacy, side effects, and comorbidities and contraindications when choosing a preventive therapy, she added. Verapamil and memantine are well tolerated and appropriate choices if the goal is to avoid side effects in general. If weight gain or fatigue is a concern, then topiramate and venlafaxine should be considered. Neurologists should avoid prescribing antiepileptic drugs if cognitive symptoms are a concern, said Dr. Burch. Beta blockers and venlafaxine would be better options in this case.

In clinical trials of CGRP therapies, the rates of adverse events were similar between the active and control arms. “But it’s become fairly clear that the clinical trials did not fully capture the side-effect profile that we are seeing in clinical practice,” said Dr. Burch. In a paper currently in review, she and her colleagues retrospectively studied 241 patients that they had treated with CGRP monoclonal antibodies at their headache center. The most common adverse events were constipation (43%), injection-site reaction (24%), muscle or joint pain (17%), and fatigue (15%). Furthermore, CGRP antagonists were associated with maternal hypertension, fetal growth restriction, and fetal mortality in animal studies. The current recommendation is to avoid CGRP monoclonal antibodies during pregnancy or in any patient who is at risk of becoming pregnant, said Dr. Burch.
 

How should neurologists assess preventive efficacy?

The assessment of a medication’s preventive efficacy “is a moving target in the headache world,” said Dr. Burch. “Historically, we have used headache days per month, and that is still, according to the International Headache Society clinical trials guidelines, how we should be judging whether a medication is working or not. But that doesn’t necessarily tell us what’s going to happen to an individual patient in front of us.”

In 2017, the Institute for Clinical Effectiveness Research compared data for old and new migraine treatments in a network meta-analysis. They all tended to reduce the number of monthly migraine days by one to two, compared with placebo. When one analyzes clinical trials of the drugs using this criterion, “most of these treatments come out about the same,” said Dr. Burch.

More recently, investigators have examined responder rates. They commonly report the proportions of patients who had a reduction in headache days of 50%, 75%, or 100%, for example. To extrapolate responder rates from the trial participants to the general population, a neurologist must know which groups of patients got worse on treatment, said Dr. Burch. Furthermore, the responder rates for older medications are unknown, because they were not examined. This situation makes comparisons of newer and older therapies more complicated.

Phase 3 trials of the CGRP drugs included analyses of the therapies’ 50% responder rates. This rate was about 42% for the 70-mg dose of erenumab and 50% for the 140-mg dose. The 50% responder rates for fremanezumab were 47.7% for the 225-mg dose and 44.4% for the 675-mg dose. In two trials of galcanezumab, the 50% responder rate for the 120-mg dose was approximately 60%, and the rate for the 240-mg dose was about 59%. The 50% responder rates for eptinezumab were 50% for the 100-mg dose and 56% for the 300-mg dose. The 50% responder rate across all trials was around 50%-60% in the active group, which is roughly 25% over the placebo group, said Dr. Burch.

Another measurement of efficacy is the efficacy-to-harm ratio, which is derived from the number needed to treat and the number needed to harm. To calculate this ratio, however, harm needs to be assessed adequately during a clinical trial. Although the ratio can provide a clinically relevant overview of a drug’s effects, patients may differ from each other in the way they evaluate efficacy and harm.

In addition, many questions about preventive treatment of migraine have no clear answers yet. It is uncertain, for example, how long a patient should receive preventive treatment and when treatment should be withdrawn, said Dr. Burch. “Can we expect that a lot of people are going to need to be on it for life, or is there a subpopulation who will get better and [for whom] we can withdraw [treatment]?” she asked. “How do we identify them?” Also, more data are needed before neurologists can understand why a given patient responds to one treatment, but not to another. It is difficult to predict which patients will respond to which treatments. Finally, it remains unclear how much of patients’ improvement can be attributed to regression to the mean, rather than preventive treatment.

egreb@mdedge.com

STOWE, VT – The preventive treatment of migraine has the potential to change patients’ lives and modify the trajectory of the disease, said Rebecca Burch, MD, staff attending neurologist at Brigham and Women’s Hospital in Boston. Clinical observation suggests that preventive treatment provides benefits for appropriately selected migraineurs, although few data confirm a modifying effect on disease course, she said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England. In her overview, Dr. Burch discussed when preventive treatment is appropriate, which patients are candidates for preventive therapy, and what the levels of evidence are for the preventive therapies.

Identifying candidates for preventive treatment

Migraine is the second most disabling condition worldwide and imposes a large social and economic burden, said Dr. Burch. Preventive therapy reduces the disability associated with migraine. It reduces headache frequency and, thus, the risk that episodic migraine will transform into chronic migraine. By reducing the number of headache days, preventive treatment also may reduce the overuse of acute medication, which is a risk factor for migraine chronification.

Neurologists can consider preventive therapy for migraineurs with frequent headaches, but the term “frequent” is not clearly defined. Common definitions include one headache per week and two headaches per month with significant disability. These definitions are based on expert consensus and do not have strong evidential support, said Dr. Burch. Preventive therapy also may be appropriate for migraineurs who overuse acute medication or who have failed acute medications. Special cases, such as patients with exceptional anxiety or disability, may also call for preventive treatment, said Dr. Burch.

Data suggest that preventive treatment for migraine is underused. The American Migraine Prevalence and Prevention study of 2007 found that half of patients who should be offered preventive treatment are currently receiving it. In 2016, the Chronic Migraine Epidemiology and Outcomes study found that 4.5% of chronic migraineurs take both acute and preventive treatment.

Other data published in Cephalalgia in 2015 indicate that adherence to migraine preventive treatment is approximately 20%. About 45% of patients discontinue medication because of side effects, and 45% cite lack of efficacy as their reason for discontinuation. Patients also mentioned cost, interactions with other medications, and the inconvenience of daily medication as other reasons for discontinuation.

Neurologists can take several steps to increase adherence to preventive treatment, said Dr. Burch. First, neurologists should confirm that patients want preventive medication. A clear discussion of the goals of preventive treatment is helpful as well. Furthermore, neurologists should explain that they are offering patients a trial, said Dr. Burch. The medication can be titrated slowly from a low dose to minimize side effects. Patients can be reassured that ineffective medications will be stopped. Neurologists can emphasize that their relationship with the patient is a partnership and that the treatment strategy will be improved over time.
 

Examining the evidence on treatments’ efficacy

Many drug classes, such as antiepileptics, antidepressants, beta blockers, neurotoxins, and calcitonin gene-related peptide (CGRP) antibodies, include therapies that are used as preventive treatments for migraine. When selecting a medication, a neurologist should start with one that is supported by Level A or Level B evidence, said Dr. Burch. Medications with Level A evidence include divalproex, topiramate, metoprolol, propranolol, erenumab, galcanezumab, fremanezumab, eptinezumab, and onabotulinumtoxinA. Medications with Level B evidence include amitriptyline, venlafaxine, memantine, lisinopril, and candesartan. Neurologists sometimes prescribe gabapentin and verapamil, although the evidence for them is Level U. Duloxetine, nortriptyline, and pregabalin also are used, but the evidence for them has not been evaluated. “We need more evidence in these areas,” said Dr. Burch.

Neurologists should consider access (e.g., cost and insurance coverage), efficacy, side effects, and comorbidities and contraindications when choosing a preventive therapy, she added. Verapamil and memantine are well tolerated and appropriate choices if the goal is to avoid side effects in general. If weight gain or fatigue is a concern, then topiramate and venlafaxine should be considered. Neurologists should avoid prescribing antiepileptic drugs if cognitive symptoms are a concern, said Dr. Burch. Beta blockers and venlafaxine would be better options in this case.

In clinical trials of CGRP therapies, the rates of adverse events were similar between the active and control arms. “But it’s become fairly clear that the clinical trials did not fully capture the side-effect profile that we are seeing in clinical practice,” said Dr. Burch. In a paper currently in review, she and her colleagues retrospectively studied 241 patients that they had treated with CGRP monoclonal antibodies at their headache center. The most common adverse events were constipation (43%), injection-site reaction (24%), muscle or joint pain (17%), and fatigue (15%). Furthermore, CGRP antagonists were associated with maternal hypertension, fetal growth restriction, and fetal mortality in animal studies. The current recommendation is to avoid CGRP monoclonal antibodies during pregnancy or in any patient who is at risk of becoming pregnant, said Dr. Burch.
 

How should neurologists assess preventive efficacy?

The assessment of a medication’s preventive efficacy “is a moving target in the headache world,” said Dr. Burch. “Historically, we have used headache days per month, and that is still, according to the International Headache Society clinical trials guidelines, how we should be judging whether a medication is working or not. But that doesn’t necessarily tell us what’s going to happen to an individual patient in front of us.”

In 2017, the Institute for Clinical Effectiveness Research compared data for old and new migraine treatments in a network meta-analysis. They all tended to reduce the number of monthly migraine days by one to two, compared with placebo. When one analyzes clinical trials of the drugs using this criterion, “most of these treatments come out about the same,” said Dr. Burch.

More recently, investigators have examined responder rates. They commonly report the proportions of patients who had a reduction in headache days of 50%, 75%, or 100%, for example. To extrapolate responder rates from the trial participants to the general population, a neurologist must know which groups of patients got worse on treatment, said Dr. Burch. Furthermore, the responder rates for older medications are unknown, because they were not examined. This situation makes comparisons of newer and older therapies more complicated.

Phase 3 trials of the CGRP drugs included analyses of the therapies’ 50% responder rates. This rate was about 42% for the 70-mg dose of erenumab and 50% for the 140-mg dose. The 50% responder rates for fremanezumab were 47.7% for the 225-mg dose and 44.4% for the 675-mg dose. In two trials of galcanezumab, the 50% responder rate for the 120-mg dose was approximately 60%, and the rate for the 240-mg dose was about 59%. The 50% responder rates for eptinezumab were 50% for the 100-mg dose and 56% for the 300-mg dose. The 50% responder rate across all trials was around 50%-60% in the active group, which is roughly 25% over the placebo group, said Dr. Burch.

Another measurement of efficacy is the efficacy-to-harm ratio, which is derived from the number needed to treat and the number needed to harm. To calculate this ratio, however, harm needs to be assessed adequately during a clinical trial. Although the ratio can provide a clinically relevant overview of a drug’s effects, patients may differ from each other in the way they evaluate efficacy and harm.

In addition, many questions about preventive treatment of migraine have no clear answers yet. It is uncertain, for example, how long a patient should receive preventive treatment and when treatment should be withdrawn, said Dr. Burch. “Can we expect that a lot of people are going to need to be on it for life, or is there a subpopulation who will get better and [for whom] we can withdraw [treatment]?” she asked. “How do we identify them?” Also, more data are needed before neurologists can understand why a given patient responds to one treatment, but not to another. It is difficult to predict which patients will respond to which treatments. Finally, it remains unclear how much of patients’ improvement can be attributed to regression to the mean, rather than preventive treatment.

egreb@mdedge.com

STOWE, VT – The preventive treatment of migraine has the potential to change patients’ lives and modify the trajectory of the disease, said Rebecca Burch, MD, staff attending neurologist at Brigham and Women’s Hospital in Boston. Clinical observation suggests that preventive treatment provides benefits for appropriately selected migraineurs, although few data confirm a modifying effect on disease course, she said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England. In her overview, Dr. Burch discussed when preventive treatment is appropriate, which patients are candidates for preventive therapy, and what the levels of evidence are for the preventive therapies.

Identifying candidates for preventive treatment

Migraine is the second most disabling condition worldwide and imposes a large social and economic burden, said Dr. Burch. Preventive therapy reduces the disability associated with migraine. It reduces headache frequency and, thus, the risk that episodic migraine will transform into chronic migraine. By reducing the number of headache days, preventive treatment also may reduce the overuse of acute medication, which is a risk factor for migraine chronification.

Neurologists can consider preventive therapy for migraineurs with frequent headaches, but the term “frequent” is not clearly defined. Common definitions include one headache per week and two headaches per month with significant disability. These definitions are based on expert consensus and do not have strong evidential support, said Dr. Burch. Preventive therapy also may be appropriate for migraineurs who overuse acute medication or who have failed acute medications. Special cases, such as patients with exceptional anxiety or disability, may also call for preventive treatment, said Dr. Burch.

Data suggest that preventive treatment for migraine is underused. The American Migraine Prevalence and Prevention study of 2007 found that half of patients who should be offered preventive treatment are currently receiving it. In 2016, the Chronic Migraine Epidemiology and Outcomes study found that 4.5% of chronic migraineurs take both acute and preventive treatment.

Other data published in Cephalalgia in 2015 indicate that adherence to migraine preventive treatment is approximately 20%. About 45% of patients discontinue medication because of side effects, and 45% cite lack of efficacy as their reason for discontinuation. Patients also mentioned cost, interactions with other medications, and the inconvenience of daily medication as other reasons for discontinuation.

Neurologists can take several steps to increase adherence to preventive treatment, said Dr. Burch. First, neurologists should confirm that patients want preventive medication. A clear discussion of the goals of preventive treatment is helpful as well. Furthermore, neurologists should explain that they are offering patients a trial, said Dr. Burch. The medication can be titrated slowly from a low dose to minimize side effects. Patients can be reassured that ineffective medications will be stopped. Neurologists can emphasize that their relationship with the patient is a partnership and that the treatment strategy will be improved over time.
 

Examining the evidence on treatments’ efficacy

Many drug classes, such as antiepileptics, antidepressants, beta blockers, neurotoxins, and calcitonin gene-related peptide (CGRP) antibodies, include therapies that are used as preventive treatments for migraine. When selecting a medication, a neurologist should start with one that is supported by Level A or Level B evidence, said Dr. Burch. Medications with Level A evidence include divalproex, topiramate, metoprolol, propranolol, erenumab, galcanezumab, fremanezumab, eptinezumab, and onabotulinumtoxinA. Medications with Level B evidence include amitriptyline, venlafaxine, memantine, lisinopril, and candesartan. Neurologists sometimes prescribe gabapentin and verapamil, although the evidence for them is Level U. Duloxetine, nortriptyline, and pregabalin also are used, but the evidence for them has not been evaluated. “We need more evidence in these areas,” said Dr. Burch.

Neurologists should consider access (e.g., cost and insurance coverage), efficacy, side effects, and comorbidities and contraindications when choosing a preventive therapy, she added. Verapamil and memantine are well tolerated and appropriate choices if the goal is to avoid side effects in general. If weight gain or fatigue is a concern, then topiramate and venlafaxine should be considered. Neurologists should avoid prescribing antiepileptic drugs if cognitive symptoms are a concern, said Dr. Burch. Beta blockers and venlafaxine would be better options in this case.

In clinical trials of CGRP therapies, the rates of adverse events were similar between the active and control arms. “But it’s become fairly clear that the clinical trials did not fully capture the side-effect profile that we are seeing in clinical practice,” said Dr. Burch. In a paper currently in review, she and her colleagues retrospectively studied 241 patients that they had treated with CGRP monoclonal antibodies at their headache center. The most common adverse events were constipation (43%), injection-site reaction (24%), muscle or joint pain (17%), and fatigue (15%). Furthermore, CGRP antagonists were associated with maternal hypertension, fetal growth restriction, and fetal mortality in animal studies. The current recommendation is to avoid CGRP monoclonal antibodies during pregnancy or in any patient who is at risk of becoming pregnant, said Dr. Burch.
 

How should neurologists assess preventive efficacy?

The assessment of a medication’s preventive efficacy “is a moving target in the headache world,” said Dr. Burch. “Historically, we have used headache days per month, and that is still, according to the International Headache Society clinical trials guidelines, how we should be judging whether a medication is working or not. But that doesn’t necessarily tell us what’s going to happen to an individual patient in front of us.”

In 2017, the Institute for Clinical Effectiveness Research compared data for old and new migraine treatments in a network meta-analysis. They all tended to reduce the number of monthly migraine days by one to two, compared with placebo. When one analyzes clinical trials of the drugs using this criterion, “most of these treatments come out about the same,” said Dr. Burch.

More recently, investigators have examined responder rates. They commonly report the proportions of patients who had a reduction in headache days of 50%, 75%, or 100%, for example. To extrapolate responder rates from the trial participants to the general population, a neurologist must know which groups of patients got worse on treatment, said Dr. Burch. Furthermore, the responder rates for older medications are unknown, because they were not examined. This situation makes comparisons of newer and older therapies more complicated.

Phase 3 trials of the CGRP drugs included analyses of the therapies’ 50% responder rates. This rate was about 42% for the 70-mg dose of erenumab and 50% for the 140-mg dose. The 50% responder rates for fremanezumab were 47.7% for the 225-mg dose and 44.4% for the 675-mg dose. In two trials of galcanezumab, the 50% responder rate for the 120-mg dose was approximately 60%, and the rate for the 240-mg dose was about 59%. The 50% responder rates for eptinezumab were 50% for the 100-mg dose and 56% for the 300-mg dose. The 50% responder rate across all trials was around 50%-60% in the active group, which is roughly 25% over the placebo group, said Dr. Burch.

Another measurement of efficacy is the efficacy-to-harm ratio, which is derived from the number needed to treat and the number needed to harm. To calculate this ratio, however, harm needs to be assessed adequately during a clinical trial. Although the ratio can provide a clinically relevant overview of a drug’s effects, patients may differ from each other in the way they evaluate efficacy and harm.

In addition, many questions about preventive treatment of migraine have no clear answers yet. It is uncertain, for example, how long a patient should receive preventive treatment and when treatment should be withdrawn, said Dr. Burch. “Can we expect that a lot of people are going to need to be on it for life, or is there a subpopulation who will get better and [for whom] we can withdraw [treatment]?” she asked. “How do we identify them?” Also, more data are needed before neurologists can understand why a given patient responds to one treatment, but not to another. It is difficult to predict which patients will respond to which treatments. Finally, it remains unclear how much of patients’ improvement can be attributed to regression to the mean, rather than preventive treatment.

egreb@mdedge.com

STOWE, VT. – Menstrual migraine is more disabling than migraine that has no association with menstruation, said Susan Hutchinson, MD, director of the Orange County Migraine and Headache Center in Irvine, Calif. Compared with headaches associated with nonmenstrual migraine, headaches resulting from menstrual migraine last longer and are more difficult to treat. They tend to be associated with morning awakening and with nausea and vomiting. But in younger women with regular menses, menstrual migraine is predictable. The disorder offers “an incredible chance to be preemptive and think about short-term preventive strategies,” Dr. Hutchinson said at the annual meeting of the Headache Cooperative of New England.

What is menstrual migraine?

Menstrual migraine occurs during the perimenstrual window, which begins at 2 days before onset of bleeding and ends at 3 days of menses. Migraine that occurs during this window at least two-thirds of the time satisfies the criteria for menstrual migraine. A prospective headache diary is recommended, but not required, for making the diagnosis, said Dr. Hutchinson.

Most women with migraine have perimenstrual exacerbation of their headaches, as well as headaches at other times of the month. This phenotype is called menstrually related migraine. Pure menstrual migraine is migraine associated exclusively with menses. The International Classification of Headache Disorders-3 recognizes that menstrual migraine can be with or without aura. A headache diary can help distinguish between menstrual migraine and menstrually related migraine.

For pure menstrual migraine, it is appropriate to treat during the perimenstrual window. Preventive treatment may not be necessary throughout the month, said Dr. Hutchinson. Furthermore, hormonal treatment is the type of therapy most likely to be effective, she added. Menstrually related migraine requires a broader approach.
 

Gathering information during the visit

A 1972 study by Somerville and colleagues indicated that a decrease in estrogen is a powerful trigger of migraine. The investigators administered estrogen (i.e., intramuscular estradiol) or progesterone during the late luteal phase to women with menstrual migraine. Among women who received estrogen, migraine onset was postponed until the estrogen level decreased. The administration of progesterone postponed bleeding, but did not affect migraine. Progesterone treatment prevents migraine effectively on occasion, but estrogen treatment is much more likely to be a successful strategy, said Dr. Hutchinson.

Neurologists should ask certain questions of women with migraine, whether the patients are new or not, to gather information needed to make treatment decisions. For example, it is advisable to ask a woman whether she often has a headache with her period. “You may not want to use the word ‘migraine,’ because many women have been taught that headache is part of PMS,” said Dr. Hutchinson. Asking a woman how pregnancy, delivery, and breastfeeding affected her headaches can add further detail to her history and provide insight about the effects of hormonal changes. Asking what type of birth control the woman is taking can influence the choice of treatment, since some therapies are not appropriate during pregnancy.
 

Available treatments

NSAIDs are among the treatments that neurologists should consider for the short-term prevention of menstrually related migraine, said Dr. Hutchinson. A study of 35 patients by Sances et al. compared placebo with 550 mg of naproxen sodium given twice daily. Treatment began at 7 days before bleeding onset and continued until the 6th day of menses. Patients underwent treatment for three menstrual cycles. Naproxen sodium significantly reduced headache intensity, headache duration, and the number of headache days, compared with baseline. Treatment was superior to placebo at 3 months. Approximately 33% of patients in the active group were headache free, but no controls were.

Magnesium is another potentially effective option. Facchinetti et al. compared placebo with 360 mg/day of magnesium in a study of 20 patients. Treatment, which was given for two cycles, began at 15 days before menses and ended at the start of menses. Compared with placebo, magnesium reduced the number of headache days and the total pain index. Magnesium is inexpensive, but it causes diarrhea in some patients. “Some women choose to take magnesium all month long, other women start at around ovulation,” said Dr. Hutchinson.

Hormonal treatments are another possible option for the short-term prevention of menstrually related migraine. For women who do not plan to become pregnant, oral contraceptive pills can keep estrogen levels high enough to prevent menstrually related migraine. Gynecologists may suggest that a woman take the pill continuously, skipping the placebo, for an entire year, but Dr. Hutchinson recommends that a woman stop taking the pill for 4 days approximately every 3 months. This discontinuation allows for withdrawal bleeding, but is not likely to cause a prolonged enough decrease in estrogen to provoke migraine, she said. The continuous contraceptive ring, which is inserted vaginally, is an alternative to the pill.

For women who do not want or need contraception, an estrogen patch or gel may be appropriate. Two studies in the 1980s found that a gel containing 1.5 mg of estradiol per 2.5 g reduced migraine frequency, duration, and severity. These studies did not gather long-term safety data, however. A 2006 study by MacGregor et al. found that percutaneous estradiol was associated with a 22% reduction in the number of migraine days, as well as with decreases in headache severity and associated nausea. But the risk of migraine during the 5 days following treatment cessation was increased by 40%. This finding suggests that the treatment period should be extended, said Dr. Hutchinson.

In addition to the timing, the dose of treatment affects the outcome. Smite et al. found no benefit of a 50-mcg dose of estradiol, compared with placebo. Pradalier and colleagues found that a 100-mcg dose was associated with decreased use of rescue medication, compared with a 25-mcg dose. These studies did not gather long-term safety data.
 

Oral contraceptives and the risk of stroke

Combined oral contraceptives, however, are associated with increased risk of stroke in women with migraine with aura. The dose of estrogen in the contraceptive affects the level of risk, said Dr. Hutchinson. A systematic review by Sheikh et al. found that high-dose ethinyl estradiol (i.e., greater than 50 mcg) was associated with a higher risk of ischemic and hemorrhagic stroke than low-dose ethinyl estradiol (i.e., less than 50 mcg) was. A 20-mcg dose was associated with an odds ratio of stroke of 1.7. Furthermore, among women using combined hormonal contraception, the risk of stroke was higher in women with aura than in women without aura.

“I like to look at the big picture,” said Dr. Hutchinson. “There’s a big difference between a woman who has one or two auras a year that last for 10 minutes and a woman who has complicated aura. I’m going to approach [the latter] woman differently.”

No consensus guidelines for prescribing combined oral contraceptives to women with migraine and aura have been developed. The International Headache Society says that physicians may prescribe low-dose estrogen to women with simple visual aura. The American College of Obstetricians and Gynecologists recommends progestin-only intrauterine or barrier contraception for this population. The World Health Organization holds that estrogen-containing contraception is contraindicated in all women who have migraine with aura.

“If you have women who have migraine without aura, low–estrogen dose combined hormonal contraceptives can be quite appropriate,” said Dr. Hutchinson. “I would tend to go with a 10- or 20-mcg low dose. It could be an option for women with migraine with aura, but only if the benefits outweigh the risks.” In a study by Calhoun et al., the vaginal ring was associated with reduced aura frequency in women with migraine and aura.
 

Choosing preventive and rescue medications

Although no triptan has FDA approval for the short-term prevention of menstrual migraine, studies have suggested that they are effective. In a study by Sances and colleagues, a twice-daily 1-mg dose of naratriptan taken 6 days perimenstrually reduced the frequency of menstrual-related migraine. At least 50% of treated patients in the study had no menstrual-related migraine. Silberstein and colleagues found that 59% of women who took 2.5 mg of frovatriptan twice daily had no menstrual-related migraine during the 6-day perimenstrual period, compared with 33% of women who received placebo.

Patients with menstrual migraine sometimes need rescue medication. Sumatriptan, either as an injection or an inhaled therapy, is one option. Another injectable option is a 60-mg intramuscular dose of ketorolac. Finally, occipital or sphenopalatine nerve block may be effective as well.

Dr. Hutchinson reported consulting for or serving on the advisory board of Alder, Allergan, Amgen, Biohaven, electroCore, Lilly, Novartis, Supernus, Teva, Theranica, and Upsher-Smith. She has served on speakers bureaus for Allergan, Amgen, electroCore, Lilly, Novartis, Supernus, and Teva.

egreb@mdedge.com

STOWE, VT. – Menstrual migraine is more disabling than migraine that has no association with menstruation, said Susan Hutchinson, MD, director of the Orange County Migraine and Headache Center in Irvine, Calif. Compared with headaches associated with nonmenstrual migraine, headaches resulting from menstrual migraine last longer and are more difficult to treat. They tend to be associated with morning awakening and with nausea and vomiting. But in younger women with regular menses, menstrual migraine is predictable. The disorder offers “an incredible chance to be preemptive and think about short-term preventive strategies,” Dr. Hutchinson said at the annual meeting of the Headache Cooperative of New England.

What is menstrual migraine?

Menstrual migraine occurs during the perimenstrual window, which begins at 2 days before onset of bleeding and ends at 3 days of menses. Migraine that occurs during this window at least two-thirds of the time satisfies the criteria for menstrual migraine. A prospective headache diary is recommended, but not required, for making the diagnosis, said Dr. Hutchinson.

Most women with migraine have perimenstrual exacerbation of their headaches, as well as headaches at other times of the month. This phenotype is called menstrually related migraine. Pure menstrual migraine is migraine associated exclusively with menses. The International Classification of Headache Disorders-3 recognizes that menstrual migraine can be with or without aura. A headache diary can help distinguish between menstrual migraine and menstrually related migraine.

For pure menstrual migraine, it is appropriate to treat during the perimenstrual window. Preventive treatment may not be necessary throughout the month, said Dr. Hutchinson. Furthermore, hormonal treatment is the type of therapy most likely to be effective, she added. Menstrually related migraine requires a broader approach.
 

Gathering information during the visit

A 1972 study by Somerville and colleagues indicated that a decrease in estrogen is a powerful trigger of migraine. The investigators administered estrogen (i.e., intramuscular estradiol) or progesterone during the late luteal phase to women with menstrual migraine. Among women who received estrogen, migraine onset was postponed until the estrogen level decreased. The administration of progesterone postponed bleeding, but did not affect migraine. Progesterone treatment prevents migraine effectively on occasion, but estrogen treatment is much more likely to be a successful strategy, said Dr. Hutchinson.

Neurologists should ask certain questions of women with migraine, whether the patients are new or not, to gather information needed to make treatment decisions. For example, it is advisable to ask a woman whether she often has a headache with her period. “You may not want to use the word ‘migraine,’ because many women have been taught that headache is part of PMS,” said Dr. Hutchinson. Asking a woman how pregnancy, delivery, and breastfeeding affected her headaches can add further detail to her history and provide insight about the effects of hormonal changes. Asking what type of birth control the woman is taking can influence the choice of treatment, since some therapies are not appropriate during pregnancy.
 

Available treatments

NSAIDs are among the treatments that neurologists should consider for the short-term prevention of menstrually related migraine, said Dr. Hutchinson. A study of 35 patients by Sances et al. compared placebo with 550 mg of naproxen sodium given twice daily. Treatment began at 7 days before bleeding onset and continued until the 6th day of menses. Patients underwent treatment for three menstrual cycles. Naproxen sodium significantly reduced headache intensity, headache duration, and the number of headache days, compared with baseline. Treatment was superior to placebo at 3 months. Approximately 33% of patients in the active group were headache free, but no controls were.

Magnesium is another potentially effective option. Facchinetti et al. compared placebo with 360 mg/day of magnesium in a study of 20 patients. Treatment, which was given for two cycles, began at 15 days before menses and ended at the start of menses. Compared with placebo, magnesium reduced the number of headache days and the total pain index. Magnesium is inexpensive, but it causes diarrhea in some patients. “Some women choose to take magnesium all month long, other women start at around ovulation,” said Dr. Hutchinson.

Hormonal treatments are another possible option for the short-term prevention of menstrually related migraine. For women who do not plan to become pregnant, oral contraceptive pills can keep estrogen levels high enough to prevent menstrually related migraine. Gynecologists may suggest that a woman take the pill continuously, skipping the placebo, for an entire year, but Dr. Hutchinson recommends that a woman stop taking the pill for 4 days approximately every 3 months. This discontinuation allows for withdrawal bleeding, but is not likely to cause a prolonged enough decrease in estrogen to provoke migraine, she said. The continuous contraceptive ring, which is inserted vaginally, is an alternative to the pill.

For women who do not want or need contraception, an estrogen patch or gel may be appropriate. Two studies in the 1980s found that a gel containing 1.5 mg of estradiol per 2.5 g reduced migraine frequency, duration, and severity. These studies did not gather long-term safety data, however. A 2006 study by MacGregor et al. found that percutaneous estradiol was associated with a 22% reduction in the number of migraine days, as well as with decreases in headache severity and associated nausea. But the risk of migraine during the 5 days following treatment cessation was increased by 40%. This finding suggests that the treatment period should be extended, said Dr. Hutchinson.

In addition to the timing, the dose of treatment affects the outcome. Smite et al. found no benefit of a 50-mcg dose of estradiol, compared with placebo. Pradalier and colleagues found that a 100-mcg dose was associated with decreased use of rescue medication, compared with a 25-mcg dose. These studies did not gather long-term safety data.
 

Oral contraceptives and the risk of stroke

Combined oral contraceptives, however, are associated with increased risk of stroke in women with migraine with aura. The dose of estrogen in the contraceptive affects the level of risk, said Dr. Hutchinson. A systematic review by Sheikh et al. found that high-dose ethinyl estradiol (i.e., greater than 50 mcg) was associated with a higher risk of ischemic and hemorrhagic stroke than low-dose ethinyl estradiol (i.e., less than 50 mcg) was. A 20-mcg dose was associated with an odds ratio of stroke of 1.7. Furthermore, among women using combined hormonal contraception, the risk of stroke was higher in women with aura than in women without aura.

“I like to look at the big picture,” said Dr. Hutchinson. “There’s a big difference between a woman who has one or two auras a year that last for 10 minutes and a woman who has complicated aura. I’m going to approach [the latter] woman differently.”

No consensus guidelines for prescribing combined oral contraceptives to women with migraine and aura have been developed. The International Headache Society says that physicians may prescribe low-dose estrogen to women with simple visual aura. The American College of Obstetricians and Gynecologists recommends progestin-only intrauterine or barrier contraception for this population. The World Health Organization holds that estrogen-containing contraception is contraindicated in all women who have migraine with aura.

“If you have women who have migraine without aura, low–estrogen dose combined hormonal contraceptives can be quite appropriate,” said Dr. Hutchinson. “I would tend to go with a 10- or 20-mcg low dose. It could be an option for women with migraine with aura, but only if the benefits outweigh the risks.” In a study by Calhoun et al., the vaginal ring was associated with reduced aura frequency in women with migraine and aura.
 

Choosing preventive and rescue medications

Although no triptan has FDA approval for the short-term prevention of menstrual migraine, studies have suggested that they are effective. In a study by Sances and colleagues, a twice-daily 1-mg dose of naratriptan taken 6 days perimenstrually reduced the frequency of menstrual-related migraine. At least 50% of treated patients in the study had no menstrual-related migraine. Silberstein and colleagues found that 59% of women who took 2.5 mg of frovatriptan twice daily had no menstrual-related migraine during the 6-day perimenstrual period, compared with 33% of women who received placebo.

Patients with menstrual migraine sometimes need rescue medication. Sumatriptan, either as an injection or an inhaled therapy, is one option. Another injectable option is a 60-mg intramuscular dose of ketorolac. Finally, occipital or sphenopalatine nerve block may be effective as well.

Dr. Hutchinson reported consulting for or serving on the advisory board of Alder, Allergan, Amgen, Biohaven, electroCore, Lilly, Novartis, Supernus, Teva, Theranica, and Upsher-Smith. She has served on speakers bureaus for Allergan, Amgen, electroCore, Lilly, Novartis, Supernus, and Teva.

egreb@mdedge.com

STOWE, VT. – Menstrual migraine is more disabling than migraine that has no association with menstruation, said Susan Hutchinson, MD, director of the Orange County Migraine and Headache Center in Irvine, Calif. Compared with headaches associated with nonmenstrual migraine, headaches resulting from menstrual migraine last longer and are more difficult to treat. They tend to be associated with morning awakening and with nausea and vomiting. But in younger women with regular menses, menstrual migraine is predictable. The disorder offers “an incredible chance to be preemptive and think about short-term preventive strategies,” Dr. Hutchinson said at the annual meeting of the Headache Cooperative of New England.

What is menstrual migraine?

Menstrual migraine occurs during the perimenstrual window, which begins at 2 days before onset of bleeding and ends at 3 days of menses. Migraine that occurs during this window at least two-thirds of the time satisfies the criteria for menstrual migraine. A prospective headache diary is recommended, but not required, for making the diagnosis, said Dr. Hutchinson.

Most women with migraine have perimenstrual exacerbation of their headaches, as well as headaches at other times of the month. This phenotype is called menstrually related migraine. Pure menstrual migraine is migraine associated exclusively with menses. The International Classification of Headache Disorders-3 recognizes that menstrual migraine can be with or without aura. A headache diary can help distinguish between menstrual migraine and menstrually related migraine.

For pure menstrual migraine, it is appropriate to treat during the perimenstrual window. Preventive treatment may not be necessary throughout the month, said Dr. Hutchinson. Furthermore, hormonal treatment is the type of therapy most likely to be effective, she added. Menstrually related migraine requires a broader approach.
 

Gathering information during the visit

A 1972 study by Somerville and colleagues indicated that a decrease in estrogen is a powerful trigger of migraine. The investigators administered estrogen (i.e., intramuscular estradiol) or progesterone during the late luteal phase to women with menstrual migraine. Among women who received estrogen, migraine onset was postponed until the estrogen level decreased. The administration of progesterone postponed bleeding, but did not affect migraine. Progesterone treatment prevents migraine effectively on occasion, but estrogen treatment is much more likely to be a successful strategy, said Dr. Hutchinson.

Neurologists should ask certain questions of women with migraine, whether the patients are new or not, to gather information needed to make treatment decisions. For example, it is advisable to ask a woman whether she often has a headache with her period. “You may not want to use the word ‘migraine,’ because many women have been taught that headache is part of PMS,” said Dr. Hutchinson. Asking a woman how pregnancy, delivery, and breastfeeding affected her headaches can add further detail to her history and provide insight about the effects of hormonal changes. Asking what type of birth control the woman is taking can influence the choice of treatment, since some therapies are not appropriate during pregnancy.
 

Available treatments

NSAIDs are among the treatments that neurologists should consider for the short-term prevention of menstrually related migraine, said Dr. Hutchinson. A study of 35 patients by Sances et al. compared placebo with 550 mg of naproxen sodium given twice daily. Treatment began at 7 days before bleeding onset and continued until the 6th day of menses. Patients underwent treatment for three menstrual cycles. Naproxen sodium significantly reduced headache intensity, headache duration, and the number of headache days, compared with baseline. Treatment was superior to placebo at 3 months. Approximately 33% of patients in the active group were headache free, but no controls were.

Magnesium is another potentially effective option. Facchinetti et al. compared placebo with 360 mg/day of magnesium in a study of 20 patients. Treatment, which was given for two cycles, began at 15 days before menses and ended at the start of menses. Compared with placebo, magnesium reduced the number of headache days and the total pain index. Magnesium is inexpensive, but it causes diarrhea in some patients. “Some women choose to take magnesium all month long, other women start at around ovulation,” said Dr. Hutchinson.

Hormonal treatments are another possible option for the short-term prevention of menstrually related migraine. For women who do not plan to become pregnant, oral contraceptive pills can keep estrogen levels high enough to prevent menstrually related migraine. Gynecologists may suggest that a woman take the pill continuously, skipping the placebo, for an entire year, but Dr. Hutchinson recommends that a woman stop taking the pill for 4 days approximately every 3 months. This discontinuation allows for withdrawal bleeding, but is not likely to cause a prolonged enough decrease in estrogen to provoke migraine, she said. The continuous contraceptive ring, which is inserted vaginally, is an alternative to the pill.

For women who do not want or need contraception, an estrogen patch or gel may be appropriate. Two studies in the 1980s found that a gel containing 1.5 mg of estradiol per 2.5 g reduced migraine frequency, duration, and severity. These studies did not gather long-term safety data, however. A 2006 study by MacGregor et al. found that percutaneous estradiol was associated with a 22% reduction in the number of migraine days, as well as with decreases in headache severity and associated nausea. But the risk of migraine during the 5 days following treatment cessation was increased by 40%. This finding suggests that the treatment period should be extended, said Dr. Hutchinson.

In addition to the timing, the dose of treatment affects the outcome. Smite et al. found no benefit of a 50-mcg dose of estradiol, compared with placebo. Pradalier and colleagues found that a 100-mcg dose was associated with decreased use of rescue medication, compared with a 25-mcg dose. These studies did not gather long-term safety data.
 

Oral contraceptives and the risk of stroke

Combined oral contraceptives, however, are associated with increased risk of stroke in women with migraine with aura. The dose of estrogen in the contraceptive affects the level of risk, said Dr. Hutchinson. A systematic review by Sheikh et al. found that high-dose ethinyl estradiol (i.e., greater than 50 mcg) was associated with a higher risk of ischemic and hemorrhagic stroke than low-dose ethinyl estradiol (i.e., less than 50 mcg) was. A 20-mcg dose was associated with an odds ratio of stroke of 1.7. Furthermore, among women using combined hormonal contraception, the risk of stroke was higher in women with aura than in women without aura.

“I like to look at the big picture,” said Dr. Hutchinson. “There’s a big difference between a woman who has one or two auras a year that last for 10 minutes and a woman who has complicated aura. I’m going to approach [the latter] woman differently.”

No consensus guidelines for prescribing combined oral contraceptives to women with migraine and aura have been developed. The International Headache Society says that physicians may prescribe low-dose estrogen to women with simple visual aura. The American College of Obstetricians and Gynecologists recommends progestin-only intrauterine or barrier contraception for this population. The World Health Organization holds that estrogen-containing contraception is contraindicated in all women who have migraine with aura.

“If you have women who have migraine without aura, low–estrogen dose combined hormonal contraceptives can be quite appropriate,” said Dr. Hutchinson. “I would tend to go with a 10- or 20-mcg low dose. It could be an option for women with migraine with aura, but only if the benefits outweigh the risks.” In a study by Calhoun et al., the vaginal ring was associated with reduced aura frequency in women with migraine and aura.
 

Choosing preventive and rescue medications

Although no triptan has FDA approval for the short-term prevention of menstrual migraine, studies have suggested that they are effective. In a study by Sances and colleagues, a twice-daily 1-mg dose of naratriptan taken 6 days perimenstrually reduced the frequency of menstrual-related migraine. At least 50% of treated patients in the study had no menstrual-related migraine. Silberstein and colleagues found that 59% of women who took 2.5 mg of frovatriptan twice daily had no menstrual-related migraine during the 6-day perimenstrual period, compared with 33% of women who received placebo.

Patients with menstrual migraine sometimes need rescue medication. Sumatriptan, either as an injection or an inhaled therapy, is one option. Another injectable option is a 60-mg intramuscular dose of ketorolac. Finally, occipital or sphenopalatine nerve block may be effective as well.

Dr. Hutchinson reported consulting for or serving on the advisory board of Alder, Allergan, Amgen, Biohaven, electroCore, Lilly, Novartis, Supernus, Teva, Theranica, and Upsher-Smith. She has served on speakers bureaus for Allergan, Amgen, electroCore, Lilly, Novartis, Supernus, and Teva.

egreb@mdedge.com

Since the Centers for Disease Control and Prevention (CDC) confirmed the first US case of novel coronavirus infection on January 20, much of the clinical focus has naturally centered on the virus’ prodromal symptoms and severe respiratory effects.

However, US neurologists are now reporting that COVID-19 symptoms may also include encephalopathy, ataxia, and other neurologic signs.

“I am hearing about strokes, ataxia, myelitis, etc,” Stephan Mayer, MD, a neurointensivist in Troy, Michigan, posted on Twitter on March 26.

Other possible signs and symptoms include subtle neurologic deficits, severe fatigue, trigeminal neuralgia, complete/severe anosmia, and myalgia as reported by clinicians who responded to the tweet.

On March 31, the first presumptive case of encephalitis linked to COVID-19 was documented in a 58-year-old woman treated at Henry Ford Health System in Detroit.

Physicians who reported the acute necrotizing hemorrhagic encephalopathy case in the journal Radiology counseled neurologists to suspect the virus in patients presenting with altered levels of consciousness.

Researchers in China also reported the first presumptive case of Guillain-Barre syndrome (GBS) associated with COVID-19. A 61-year-old woman initially presented with signs of the autoimmune neuropathy GBS, including leg weakness, and severe fatigue after returning from Wuhan, China. She did not initially present with the common COVID-19 symptoms of fever, cough, or chest pain.

Her muscle weakness and distal areflexia progressed over time. On day 8, the patient developed more characteristic COVID-19 signs, including ‘ground glass’ lung opacities, dry cough, and fever. She was treated with antivirals, immunoglobulins, and supportive care, recovering slowly until discharge on day 30.

“Our single-case report only suggests a possible association between GBS and SARS-CoV-2 infection. It may or may not have causal relationship. More cases with epidemiological data are necessary,” said senior author Sheng Chen, MD, PhD.

However, “we still suggest physicians who encounter acute GBS patients from pandemic areas protect themselves carefully and test for the virus on admission. If the results are positive, the patient needs to be isolated,” added Dr. Chen, a neurologist at Shanghai Ruijin Hospital and Shanghai Jiao Tong University School of Medicine in China.

Neurologic presentations of COVID-19 “are not common, but could happen,” Dr. Chen added. Headache, muscle weakness, and myalgias have been documented in other patients in China, he said.
 

Early days

Despite this growing number of anecdotal reports and observational data documenting neurologic effects, the majority of patients with COVID-19 do not present with such symptoms.

“Most COVID-19 patients we have seen have a normal neurological presentation. Abnormal neurological findings we have seen include loss of smell and taste sensation, and states of altered mental status including confusion, lethargy, and coma,” said Robert Stevens, MD, who focuses on neuroscience critical care at the Johns Hopkins School of Medicine in Baltimore, Maryland.

Other groups are reporting seizures, spinal cord disease, and brain stem disease. It has been suggested that brain stem dysfunction may account for the loss of hypoxic respiratory drive seen in a subset of patients with severe COVID-19 disease, he added.

However, Dr. Stevens, who plans to track neurologic outcomes in COVID-19 patients, also cautioned that it’s still early and these case reports are preliminary.

“An important caveat is that our knowledge of the different neurological presentations reported in association with COVID-19 is purely descriptive. We know almost nothing about the potential interactions between COVID-19 and the nervous system,” he noted.

He added it’s likely that some of the neurologic phenomena in COVID-19 are not causally related to the virus.

“This is why we have decided to establish a multisite neuro–COVID-19 data registry, so that we can gain epidemiological and mechanistic insight on these phenomena,” he said.

Nevertheless, in an online report February 27 in the Journal of Medical Virology, Yan-Chao Li, MD, and colleagues wrote that “increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system, inducing neurological diseases.”

Dr. Li is affiliated with the Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine, Jilin University, Changchun, China.
 

A global view

Scientists observed SARS-CoV in the brains of infected people and animals, particularly the brainstem, they noted. Given the similarity of SARS-CoV to SARS-CoV-2, the virus that causes COVID-19, the researchers suggest a similar invasive mechanism could be occurring in some patients.

Although it hasn’t been proven, Dr. Li and colleagues suggest COVID-19 could act beyond receptors in the lungs, traveling via “a synapse‐connected route to the medullary cardiorespiratory center” in the brain. This action, in turn, could add to the acute respiratory failure observed in many people with COVID-19.

Other neurologists tracking and monitoring case reports of neurologic symptoms potentially related to COVID-19 include Dr. Mayer and Amelia Boehme, PhD, MSPH, an epidemiologist at Columbia University specializing in stroke and cardiovascular disease.

Dr. Boehme suggested on Twitter that the neurology community conduct a multicenter study to examine the relationship between the virus and neurologic symptoms/sequelae.

Medscape Medical News interviewed Michel Dib, MD, a neurologist at the Pitié Salpêtrière hospital in Paris, who said primary neurologic presentations of COVID-19 occur rarely – and primarily in older adults. As other clinicians note, these include confusion and disorientation. He also reports cases of encephalitis and one patient who initially presented with epilepsy.

Initial reports also came from neurologists in countries where COVID-19 struck first. For example, stroke, delirium, epileptic seizures and more are being treated by neurologists at the University of Brescia in Italy in a dedicated unit designed to treat both COVID-19 and neurologic syndromes, Alessandro Pezzini, MD, reported in Neurology Today, a publication of the American Academy of Neurology.

Dr. Pezzini noted that the mechanisms behind the observed increase in vascular complications warrant further investigation. He and colleagues are planning a multicenter study in Italy to dive deeper into the central nervous system effects of COVID-19 infection.

Clinicians in China also report neurologic symptoms in some patients. A study of 221 consecutive COVID-19 patients in Wuhan revealed 11 patients developed acute ischemic stroke, one experienced cerebral venous sinus thrombosis, and another experienced cerebral hemorrhage.

Older age and more severe disease were associated with a greater likelihood for cerebrovascular disease, the authors reported.

Drs. Chen and Li have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Since the Centers for Disease Control and Prevention (CDC) confirmed the first US case of novel coronavirus infection on January 20, much of the clinical focus has naturally centered on the virus’ prodromal symptoms and severe respiratory effects.

However, US neurologists are now reporting that COVID-19 symptoms may also include encephalopathy, ataxia, and other neurologic signs.

“I am hearing about strokes, ataxia, myelitis, etc,” Stephan Mayer, MD, a neurointensivist in Troy, Michigan, posted on Twitter on March 26.

Other possible signs and symptoms include subtle neurologic deficits, severe fatigue, trigeminal neuralgia, complete/severe anosmia, and myalgia as reported by clinicians who responded to the tweet.

On March 31, the first presumptive case of encephalitis linked to COVID-19 was documented in a 58-year-old woman treated at Henry Ford Health System in Detroit.

Physicians who reported the acute necrotizing hemorrhagic encephalopathy case in the journal Radiology counseled neurologists to suspect the virus in patients presenting with altered levels of consciousness.

Researchers in China also reported the first presumptive case of Guillain-Barre syndrome (GBS) associated with COVID-19. A 61-year-old woman initially presented with signs of the autoimmune neuropathy GBS, including leg weakness, and severe fatigue after returning from Wuhan, China. She did not initially present with the common COVID-19 symptoms of fever, cough, or chest pain.

Her muscle weakness and distal areflexia progressed over time. On day 8, the patient developed more characteristic COVID-19 signs, including ‘ground glass’ lung opacities, dry cough, and fever. She was treated with antivirals, immunoglobulins, and supportive care, recovering slowly until discharge on day 30.

“Our single-case report only suggests a possible association between GBS and SARS-CoV-2 infection. It may or may not have causal relationship. More cases with epidemiological data are necessary,” said senior author Sheng Chen, MD, PhD.

However, “we still suggest physicians who encounter acute GBS patients from pandemic areas protect themselves carefully and test for the virus on admission. If the results are positive, the patient needs to be isolated,” added Dr. Chen, a neurologist at Shanghai Ruijin Hospital and Shanghai Jiao Tong University School of Medicine in China.

Neurologic presentations of COVID-19 “are not common, but could happen,” Dr. Chen added. Headache, muscle weakness, and myalgias have been documented in other patients in China, he said.
 

Early days

Despite this growing number of anecdotal reports and observational data documenting neurologic effects, the majority of patients with COVID-19 do not present with such symptoms.

“Most COVID-19 patients we have seen have a normal neurological presentation. Abnormal neurological findings we have seen include loss of smell and taste sensation, and states of altered mental status including confusion, lethargy, and coma,” said Robert Stevens, MD, who focuses on neuroscience critical care at the Johns Hopkins School of Medicine in Baltimore, Maryland.

Other groups are reporting seizures, spinal cord disease, and brain stem disease. It has been suggested that brain stem dysfunction may account for the loss of hypoxic respiratory drive seen in a subset of patients with severe COVID-19 disease, he added.

However, Dr. Stevens, who plans to track neurologic outcomes in COVID-19 patients, also cautioned that it’s still early and these case reports are preliminary.

“An important caveat is that our knowledge of the different neurological presentations reported in association with COVID-19 is purely descriptive. We know almost nothing about the potential interactions between COVID-19 and the nervous system,” he noted.

He added it’s likely that some of the neurologic phenomena in COVID-19 are not causally related to the virus.

“This is why we have decided to establish a multisite neuro–COVID-19 data registry, so that we can gain epidemiological and mechanistic insight on these phenomena,” he said.

Nevertheless, in an online report February 27 in the Journal of Medical Virology, Yan-Chao Li, MD, and colleagues wrote that “increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system, inducing neurological diseases.”

Dr. Li is affiliated with the Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine, Jilin University, Changchun, China.
 

A global view

Scientists observed SARS-CoV in the brains of infected people and animals, particularly the brainstem, they noted. Given the similarity of SARS-CoV to SARS-CoV-2, the virus that causes COVID-19, the researchers suggest a similar invasive mechanism could be occurring in some patients.

Although it hasn’t been proven, Dr. Li and colleagues suggest COVID-19 could act beyond receptors in the lungs, traveling via “a synapse‐connected route to the medullary cardiorespiratory center” in the brain. This action, in turn, could add to the acute respiratory failure observed in many people with COVID-19.

Other neurologists tracking and monitoring case reports of neurologic symptoms potentially related to COVID-19 include Dr. Mayer and Amelia Boehme, PhD, MSPH, an epidemiologist at Columbia University specializing in stroke and cardiovascular disease.

Dr. Boehme suggested on Twitter that the neurology community conduct a multicenter study to examine the relationship between the virus and neurologic symptoms/sequelae.

Medscape Medical News interviewed Michel Dib, MD, a neurologist at the Pitié Salpêtrière hospital in Paris, who said primary neurologic presentations of COVID-19 occur rarely – and primarily in older adults. As other clinicians note, these include confusion and disorientation. He also reports cases of encephalitis and one patient who initially presented with epilepsy.

Initial reports also came from neurologists in countries where COVID-19 struck first. For example, stroke, delirium, epileptic seizures and more are being treated by neurologists at the University of Brescia in Italy in a dedicated unit designed to treat both COVID-19 and neurologic syndromes, Alessandro Pezzini, MD, reported in Neurology Today, a publication of the American Academy of Neurology.

Dr. Pezzini noted that the mechanisms behind the observed increase in vascular complications warrant further investigation. He and colleagues are planning a multicenter study in Italy to dive deeper into the central nervous system effects of COVID-19 infection.

Clinicians in China also report neurologic symptoms in some patients. A study of 221 consecutive COVID-19 patients in Wuhan revealed 11 patients developed acute ischemic stroke, one experienced cerebral venous sinus thrombosis, and another experienced cerebral hemorrhage.

Older age and more severe disease were associated with a greater likelihood for cerebrovascular disease, the authors reported.

Drs. Chen and Li have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Since the Centers for Disease Control and Prevention (CDC) confirmed the first US case of novel coronavirus infection on January 20, much of the clinical focus has naturally centered on the virus’ prodromal symptoms and severe respiratory effects.

However, US neurologists are now reporting that COVID-19 symptoms may also include encephalopathy, ataxia, and other neurologic signs.

“I am hearing about strokes, ataxia, myelitis, etc,” Stephan Mayer, MD, a neurointensivist in Troy, Michigan, posted on Twitter on March 26.

Other possible signs and symptoms include subtle neurologic deficits, severe fatigue, trigeminal neuralgia, complete/severe anosmia, and myalgia as reported by clinicians who responded to the tweet.

On March 31, the first presumptive case of encephalitis linked to COVID-19 was documented in a 58-year-old woman treated at Henry Ford Health System in Detroit.

Physicians who reported the acute necrotizing hemorrhagic encephalopathy case in the journal Radiology counseled neurologists to suspect the virus in patients presenting with altered levels of consciousness.

Researchers in China also reported the first presumptive case of Guillain-Barre syndrome (GBS) associated with COVID-19. A 61-year-old woman initially presented with signs of the autoimmune neuropathy GBS, including leg weakness, and severe fatigue after returning from Wuhan, China. She did not initially present with the common COVID-19 symptoms of fever, cough, or chest pain.

Her muscle weakness and distal areflexia progressed over time. On day 8, the patient developed more characteristic COVID-19 signs, including ‘ground glass’ lung opacities, dry cough, and fever. She was treated with antivirals, immunoglobulins, and supportive care, recovering slowly until discharge on day 30.

“Our single-case report only suggests a possible association between GBS and SARS-CoV-2 infection. It may or may not have causal relationship. More cases with epidemiological data are necessary,” said senior author Sheng Chen, MD, PhD.

However, “we still suggest physicians who encounter acute GBS patients from pandemic areas protect themselves carefully and test for the virus on admission. If the results are positive, the patient needs to be isolated,” added Dr. Chen, a neurologist at Shanghai Ruijin Hospital and Shanghai Jiao Tong University School of Medicine in China.

Neurologic presentations of COVID-19 “are not common, but could happen,” Dr. Chen added. Headache, muscle weakness, and myalgias have been documented in other patients in China, he said.
 

Early days

Despite this growing number of anecdotal reports and observational data documenting neurologic effects, the majority of patients with COVID-19 do not present with such symptoms.

“Most COVID-19 patients we have seen have a normal neurological presentation. Abnormal neurological findings we have seen include loss of smell and taste sensation, and states of altered mental status including confusion, lethargy, and coma,” said Robert Stevens, MD, who focuses on neuroscience critical care at the Johns Hopkins School of Medicine in Baltimore, Maryland.

Other groups are reporting seizures, spinal cord disease, and brain stem disease. It has been suggested that brain stem dysfunction may account for the loss of hypoxic respiratory drive seen in a subset of patients with severe COVID-19 disease, he added.

However, Dr. Stevens, who plans to track neurologic outcomes in COVID-19 patients, also cautioned that it’s still early and these case reports are preliminary.

“An important caveat is that our knowledge of the different neurological presentations reported in association with COVID-19 is purely descriptive. We know almost nothing about the potential interactions between COVID-19 and the nervous system,” he noted.

He added it’s likely that some of the neurologic phenomena in COVID-19 are not causally related to the virus.

“This is why we have decided to establish a multisite neuro–COVID-19 data registry, so that we can gain epidemiological and mechanistic insight on these phenomena,” he said.

Nevertheless, in an online report February 27 in the Journal of Medical Virology, Yan-Chao Li, MD, and colleagues wrote that “increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system, inducing neurological diseases.”

Dr. Li is affiliated with the Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine, Jilin University, Changchun, China.
 

A global view

Scientists observed SARS-CoV in the brains of infected people and animals, particularly the brainstem, they noted. Given the similarity of SARS-CoV to SARS-CoV-2, the virus that causes COVID-19, the researchers suggest a similar invasive mechanism could be occurring in some patients.

Although it hasn’t been proven, Dr. Li and colleagues suggest COVID-19 could act beyond receptors in the lungs, traveling via “a synapse‐connected route to the medullary cardiorespiratory center” in the brain. This action, in turn, could add to the acute respiratory failure observed in many people with COVID-19.

Other neurologists tracking and monitoring case reports of neurologic symptoms potentially related to COVID-19 include Dr. Mayer and Amelia Boehme, PhD, MSPH, an epidemiologist at Columbia University specializing in stroke and cardiovascular disease.

Dr. Boehme suggested on Twitter that the neurology community conduct a multicenter study to examine the relationship between the virus and neurologic symptoms/sequelae.

Medscape Medical News interviewed Michel Dib, MD, a neurologist at the Pitié Salpêtrière hospital in Paris, who said primary neurologic presentations of COVID-19 occur rarely – and primarily in older adults. As other clinicians note, these include confusion and disorientation. He also reports cases of encephalitis and one patient who initially presented with epilepsy.

Initial reports also came from neurologists in countries where COVID-19 struck first. For example, stroke, delirium, epileptic seizures and more are being treated by neurologists at the University of Brescia in Italy in a dedicated unit designed to treat both COVID-19 and neurologic syndromes, Alessandro Pezzini, MD, reported in Neurology Today, a publication of the American Academy of Neurology.

Dr. Pezzini noted that the mechanisms behind the observed increase in vascular complications warrant further investigation. He and colleagues are planning a multicenter study in Italy to dive deeper into the central nervous system effects of COVID-19 infection.

Clinicians in China also report neurologic symptoms in some patients. A study of 221 consecutive COVID-19 patients in Wuhan revealed 11 patients developed acute ischemic stroke, one experienced cerebral venous sinus thrombosis, and another experienced cerebral hemorrhage.

Older age and more severe disease were associated with a greater likelihood for cerebrovascular disease, the authors reported.

Drs. Chen and Li have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Telephone-based cognitive behavioral therapy (CBT) significantly improves depression, anxiety, and quality of life in patients with Parkinson’s disease, relative to usual care, according to trial results published in Neurology. The treatment’s effect on depression is “moderated by the reduction of negative thoughts,” the target of the intervention, the researchers said.

Telephone-based CBT may be a convenient option for patients, said lead study author Roseanne D. Dobkin, PhD, of the department of psychiatry at Rutgers Robert Wood Johnson Medical School in Piscataway, N.J., and the VA New Jersey Health Care System in Lyons. “A notable proportion of people with Parkinson’s [disease] do not receive the much needed mental health treatment to facilitate proactive coping with the daily challenges superimposed by their medical condition,” Dr. Dobkin said in a news release. “This study suggests that the effects of the [CBT] last long beyond when the treatment stopped and can be used alongside standard neurological care.”

An undertreated problem

Although depression affects about half of patients with Parkinson’s disease and is associated with physical and cognitive decline, it often goes overlooked and undertreated, the study authors said. Data about the efficacy and tolerability of antidepressants are mixed. CBT holds promise for reducing depression in Parkinson’s disease, prior research suggests, but patients may have limited access to in-person sessions because of physical and geographic barriers.

To assess the efficacy of telephone-based CBT for depression in Parkinson’s disease, compared with community-based treatment as usual, Dr. Dobkin and colleagues conducted a randomized controlled trial. Their study included 72 patients with Parkinson’s disease at an academic medical center. Participants had a depressive disorder, were between aged 35 and 85 years, had stable Parkinson’s disease and mental health treatment for at least 6 weeks, and had a family member or friend willing to participate in the study. The investigators excluded patients with possible dementia or marked cognitive impairment and active suicidal plans or intent.

Participants were randomly assigned to receive usual care plus telephone-based CBT or usual care only. Patients taking antidepressants were evenly divided between the groups.

Telephone-based CBT consisted of weekly 1-hour sessions for 10 weeks. During 6 months of follow-up, patients could receive one session per month if desired. The CBT “targeted negative thoughts (e.g., ‘I have no control’; ‘I am helpless’) and behaviors (e.g., avoidance, excessive worry, lack of exercise),” the investigators said. In addition, therapists trained patients’ care partners by telephone to help patients between sessions. Treatment as usual was defined by patients’ health care teams. For most participants in both groups, treatment as usual included taking antidepressant medication or receiving psychotherapy in the community.

Change in Hamilton Depression Rating Scale (HAM-D) score was the primary outcome. Secondary outcomes included whether patients considered their depression much improved and improvements in depression severity (as measured by the Beck Depression Inventory [BDI]), anxiety (as measured by the Hamilton Anxiety Rating Scale [HAM-A]), and quality of life. The researchers also assessed negative thinking using the Inference Questionnaire. Blinded raters assessed outcomes.
 

Sustained improvements

Thirty-seven patients were randomized to receive telephone-based CBT, and 35 were randomized to treatment as usual. Overall, 70% were taking antidepressants, and 14% continued receiving psychotherapy from community providers of their choice during the trial. Participants’ average age was 65 years, and 51% were female.

Post treatment, mean improvement in HAM-D score from baseline was 6.53 points in the telephone-based CBT group, compared with −0.27 points in the control group. “Effects at the end of treatment were maintained at 6-month follow-up,” the researchers reported.

About 40% of patients in the CBT group reported that their depression was much improved or very much improved, compared with none of the patients in the control group. Responders had mild to minimal symptomatology on the HAM-D, which indicates that the changes were clinically significant, the authors said.

Secondary outcomes also favored telephone-based CBT. “The intervention was feasible and highly acceptable, yielding an 88% retention rate over the 9-month trial,” Dr. Dobkin and colleagues said.

Compared with other control conditions, treatment-as-usual controls may enhance the effect size of an intervention, the authors noted. In addition, factors such as therapeutic relationship, time, and attention likely contribute to psychotherapy outcomes.
 

Success may hinge on cognitive ability

“The success of this trial highlights the need for further efficacy studies targeting neuropsychiatric manifestations of [Parkinson’s disease] and adds urgency to the discussion over policies regarding access to tele–mental health, especially for vulnerable populations with limited access to in-person mental health services,” Gregory M. Pontone, MD, and Kelly A. Mills, MD, wrote in an accompanying editorial. Dr. Pontone and Dr. Mills are affiliated with Johns Hopkins University in Baltimore.

“Only rudimentary evidence” exists to guide the treatment of depression in patients with Parkinson’s disease, the editorialists said. “Patient preference and tolerability suggest that nonpharmacologic therapies, such as CBT, are preferred as first-line treatment. Yet access to qualified CBT practitioners, especially those with a clinical knowledge of [Parkinson’s disease], is limited.”

Despite its advantages and the encouraging results, CBT may have important limitations as well, they said. Patients require a certain degree of cognitive ability to benefit from CBT, and the prevalence of dementia among patients with Parkinson’s disease is about 30%.

Nevertheless, the trial provided evidence of target engagement. “Though caveats include the single-blind design and potential confounding by time spent with patient and caregiver, the authors demonstrated that improvement was mediated by the mechanism of CBT – a reduction in negative thinking.”

The trial was funded by the Michael J. Fox Foundation for Parkinson’s Research and the Parkinson’s Alliance (Parkinson’s Unity Walk). Dr. Mills disclosed a patent pending for a system for phase-dependent cortical brain stimulation, National Institutes of Health funding, pending funding from the Michael J. Fox Foundation, and commercial research support from Global Kinetics Corporation. Dr. Pontone is a consultant for Acadia Pharmaceuticals.

jremaly@mdedge.com

SOURCE: Dobkin RD et al. Neurology. 2020 Apr 1. doi: 10.1212/WNL.0000000000009292.

Telephone-based cognitive behavioral therapy (CBT) significantly improves depression, anxiety, and quality of life in patients with Parkinson’s disease, relative to usual care, according to trial results published in Neurology. The treatment’s effect on depression is “moderated by the reduction of negative thoughts,” the target of the intervention, the researchers said.

Telephone-based CBT may be a convenient option for patients, said lead study author Roseanne D. Dobkin, PhD, of the department of psychiatry at Rutgers Robert Wood Johnson Medical School in Piscataway, N.J., and the VA New Jersey Health Care System in Lyons. “A notable proportion of people with Parkinson’s [disease] do not receive the much needed mental health treatment to facilitate proactive coping with the daily challenges superimposed by their medical condition,” Dr. Dobkin said in a news release. “This study suggests that the effects of the [CBT] last long beyond when the treatment stopped and can be used alongside standard neurological care.”

An undertreated problem

Although depression affects about half of patients with Parkinson’s disease and is associated with physical and cognitive decline, it often goes overlooked and undertreated, the study authors said. Data about the efficacy and tolerability of antidepressants are mixed. CBT holds promise for reducing depression in Parkinson’s disease, prior research suggests, but patients may have limited access to in-person sessions because of physical and geographic barriers.

To assess the efficacy of telephone-based CBT for depression in Parkinson’s disease, compared with community-based treatment as usual, Dr. Dobkin and colleagues conducted a randomized controlled trial. Their study included 72 patients with Parkinson’s disease at an academic medical center. Participants had a depressive disorder, were between aged 35 and 85 years, had stable Parkinson’s disease and mental health treatment for at least 6 weeks, and had a family member or friend willing to participate in the study. The investigators excluded patients with possible dementia or marked cognitive impairment and active suicidal plans or intent.

Participants were randomly assigned to receive usual care plus telephone-based CBT or usual care only. Patients taking antidepressants were evenly divided between the groups.

Telephone-based CBT consisted of weekly 1-hour sessions for 10 weeks. During 6 months of follow-up, patients could receive one session per month if desired. The CBT “targeted negative thoughts (e.g., ‘I have no control’; ‘I am helpless’) and behaviors (e.g., avoidance, excessive worry, lack of exercise),” the investigators said. In addition, therapists trained patients’ care partners by telephone to help patients between sessions. Treatment as usual was defined by patients’ health care teams. For most participants in both groups, treatment as usual included taking antidepressant medication or receiving psychotherapy in the community.

Change in Hamilton Depression Rating Scale (HAM-D) score was the primary outcome. Secondary outcomes included whether patients considered their depression much improved and improvements in depression severity (as measured by the Beck Depression Inventory [BDI]), anxiety (as measured by the Hamilton Anxiety Rating Scale [HAM-A]), and quality of life. The researchers also assessed negative thinking using the Inference Questionnaire. Blinded raters assessed outcomes.
 

Sustained improvements

Thirty-seven patients were randomized to receive telephone-based CBT, and 35 were randomized to treatment as usual. Overall, 70% were taking antidepressants, and 14% continued receiving psychotherapy from community providers of their choice during the trial. Participants’ average age was 65 years, and 51% were female.

Post treatment, mean improvement in HAM-D score from baseline was 6.53 points in the telephone-based CBT group, compared with −0.27 points in the control group. “Effects at the end of treatment were maintained at 6-month follow-up,” the researchers reported.

About 40% of patients in the CBT group reported that their depression was much improved or very much improved, compared with none of the patients in the control group. Responders had mild to minimal symptomatology on the HAM-D, which indicates that the changes were clinically significant, the authors said.

Secondary outcomes also favored telephone-based CBT. “The intervention was feasible and highly acceptable, yielding an 88% retention rate over the 9-month trial,” Dr. Dobkin and colleagues said.

Compared with other control conditions, treatment-as-usual controls may enhance the effect size of an intervention, the authors noted. In addition, factors such as therapeutic relationship, time, and attention likely contribute to psychotherapy outcomes.
 

Success may hinge on cognitive ability

“The success of this trial highlights the need for further efficacy studies targeting neuropsychiatric manifestations of [Parkinson’s disease] and adds urgency to the discussion over policies regarding access to tele–mental health, especially for vulnerable populations with limited access to in-person mental health services,” Gregory M. Pontone, MD, and Kelly A. Mills, MD, wrote in an accompanying editorial. Dr. Pontone and Dr. Mills are affiliated with Johns Hopkins University in Baltimore.

“Only rudimentary evidence” exists to guide the treatment of depression in patients with Parkinson’s disease, the editorialists said. “Patient preference and tolerability suggest that nonpharmacologic therapies, such as CBT, are preferred as first-line treatment. Yet access to qualified CBT practitioners, especially those with a clinical knowledge of [Parkinson’s disease], is limited.”

Despite its advantages and the encouraging results, CBT may have important limitations as well, they said. Patients require a certain degree of cognitive ability to benefit from CBT, and the prevalence of dementia among patients with Parkinson’s disease is about 30%.

Nevertheless, the trial provided evidence of target engagement. “Though caveats include the single-blind design and potential confounding by time spent with patient and caregiver, the authors demonstrated that improvement was mediated by the mechanism of CBT – a reduction in negative thinking.”

The trial was funded by the Michael J. Fox Foundation for Parkinson’s Research and the Parkinson’s Alliance (Parkinson’s Unity Walk). Dr. Mills disclosed a patent pending for a system for phase-dependent cortical brain stimulation, National Institutes of Health funding, pending funding from the Michael J. Fox Foundation, and commercial research support from Global Kinetics Corporation. Dr. Pontone is a consultant for Acadia Pharmaceuticals.

jremaly@mdedge.com

SOURCE: Dobkin RD et al. Neurology. 2020 Apr 1. doi: 10.1212/WNL.0000000000009292.

Telephone-based cognitive behavioral therapy (CBT) significantly improves depression, anxiety, and quality of life in patients with Parkinson’s disease, relative to usual care, according to trial results published in Neurology. The treatment’s effect on depression is “moderated by the reduction of negative thoughts,” the target of the intervention, the researchers said.

Telephone-based CBT may be a convenient option for patients, said lead study author Roseanne D. Dobkin, PhD, of the department of psychiatry at Rutgers Robert Wood Johnson Medical School in Piscataway, N.J., and the VA New Jersey Health Care System in Lyons. “A notable proportion of people with Parkinson’s [disease] do not receive the much needed mental health treatment to facilitate proactive coping with the daily challenges superimposed by their medical condition,” Dr. Dobkin said in a news release. “This study suggests that the effects of the [CBT] last long beyond when the treatment stopped and can be used alongside standard neurological care.”

An undertreated problem

Although depression affects about half of patients with Parkinson’s disease and is associated with physical and cognitive decline, it often goes overlooked and undertreated, the study authors said. Data about the efficacy and tolerability of antidepressants are mixed. CBT holds promise for reducing depression in Parkinson’s disease, prior research suggests, but patients may have limited access to in-person sessions because of physical and geographic barriers.

To assess the efficacy of telephone-based CBT for depression in Parkinson’s disease, compared with community-based treatment as usual, Dr. Dobkin and colleagues conducted a randomized controlled trial. Their study included 72 patients with Parkinson’s disease at an academic medical center. Participants had a depressive disorder, were between aged 35 and 85 years, had stable Parkinson’s disease and mental health treatment for at least 6 weeks, and had a family member or friend willing to participate in the study. The investigators excluded patients with possible dementia or marked cognitive impairment and active suicidal plans or intent.

Participants were randomly assigned to receive usual care plus telephone-based CBT or usual care only. Patients taking antidepressants were evenly divided between the groups.

Telephone-based CBT consisted of weekly 1-hour sessions for 10 weeks. During 6 months of follow-up, patients could receive one session per month if desired. The CBT “targeted negative thoughts (e.g., ‘I have no control’; ‘I am helpless’) and behaviors (e.g., avoidance, excessive worry, lack of exercise),” the investigators said. In addition, therapists trained patients’ care partners by telephone to help patients between sessions. Treatment as usual was defined by patients’ health care teams. For most participants in both groups, treatment as usual included taking antidepressant medication or receiving psychotherapy in the community.

Change in Hamilton Depression Rating Scale (HAM-D) score was the primary outcome. Secondary outcomes included whether patients considered their depression much improved and improvements in depression severity (as measured by the Beck Depression Inventory [BDI]), anxiety (as measured by the Hamilton Anxiety Rating Scale [HAM-A]), and quality of life. The researchers also assessed negative thinking using the Inference Questionnaire. Blinded raters assessed outcomes.
 

Sustained improvements

Thirty-seven patients were randomized to receive telephone-based CBT, and 35 were randomized to treatment as usual. Overall, 70% were taking antidepressants, and 14% continued receiving psychotherapy from community providers of their choice during the trial. Participants’ average age was 65 years, and 51% were female.

Post treatment, mean improvement in HAM-D score from baseline was 6.53 points in the telephone-based CBT group, compared with −0.27 points in the control group. “Effects at the end of treatment were maintained at 6-month follow-up,” the researchers reported.

About 40% of patients in the CBT group reported that their depression was much improved or very much improved, compared with none of the patients in the control group. Responders had mild to minimal symptomatology on the HAM-D, which indicates that the changes were clinically significant, the authors said.

Secondary outcomes also favored telephone-based CBT. “The intervention was feasible and highly acceptable, yielding an 88% retention rate over the 9-month trial,” Dr. Dobkin and colleagues said.

Compared with other control conditions, treatment-as-usual controls may enhance the effect size of an intervention, the authors noted. In addition, factors such as therapeutic relationship, time, and attention likely contribute to psychotherapy outcomes.
 

Success may hinge on cognitive ability

“The success of this trial highlights the need for further efficacy studies targeting neuropsychiatric manifestations of [Parkinson’s disease] and adds urgency to the discussion over policies regarding access to tele–mental health, especially for vulnerable populations with limited access to in-person mental health services,” Gregory M. Pontone, MD, and Kelly A. Mills, MD, wrote in an accompanying editorial. Dr. Pontone and Dr. Mills are affiliated with Johns Hopkins University in Baltimore.

“Only rudimentary evidence” exists to guide the treatment of depression in patients with Parkinson’s disease, the editorialists said. “Patient preference and tolerability suggest that nonpharmacologic therapies, such as CBT, are preferred as first-line treatment. Yet access to qualified CBT practitioners, especially those with a clinical knowledge of [Parkinson’s disease], is limited.”

Despite its advantages and the encouraging results, CBT may have important limitations as well, they said. Patients require a certain degree of cognitive ability to benefit from CBT, and the prevalence of dementia among patients with Parkinson’s disease is about 30%.

Nevertheless, the trial provided evidence of target engagement. “Though caveats include the single-blind design and potential confounding by time spent with patient and caregiver, the authors demonstrated that improvement was mediated by the mechanism of CBT – a reduction in negative thinking.”

The trial was funded by the Michael J. Fox Foundation for Parkinson’s Research and the Parkinson’s Alliance (Parkinson’s Unity Walk). Dr. Mills disclosed a patent pending for a system for phase-dependent cortical brain stimulation, National Institutes of Health funding, pending funding from the Michael J. Fox Foundation, and commercial research support from Global Kinetics Corporation. Dr. Pontone is a consultant for Acadia Pharmaceuticals.

jremaly@mdedge.com

SOURCE: Dobkin RD et al. Neurology. 2020 Apr 1. doi: 10.1212/WNL.0000000000009292.

The Food and Drug Administration has updated the labels for peginterferon beta-1a (Plegridy) and interferon beta-1a (Avonex) to include more information about usage of these medications during pregnancy and breastfeeding in women with multiple sclerosis (MS).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The FDA based the decision on data from more than 1,000 real-world pregnancies, including pregnancies from a large epidemiologic study and published studies over several decades, which found no connection between use of interferon-beta products during early pregnancy and an increased risk of major birth defects, according to the FDA.

As a result, the labels for both medications will no longer have the pregnancy category C designation; however, patients should continue to notify their health care provider if they are pregnant or plan to become pregnant.

The FDA decision to remove the warning follows a similar decision by the European Medicines Agency last year.

“Many women with MS are diagnosed during their childbearing years. With this important update for Plegridy and Avonex, healthcare providers have more data to inform appropriate treatment paths for patients who may be pregnant or planning for pregnancy,” said Bernd Kieseier, MD, MHBA, executive director and head of global MS at Worldwide Medical, Biogen, in a press release.

lfranki@mdedge.com

The Food and Drug Administration has updated the labels for peginterferon beta-1a (Plegridy) and interferon beta-1a (Avonex) to include more information about usage of these medications during pregnancy and breastfeeding in women with multiple sclerosis (MS).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The FDA based the decision on data from more than 1,000 real-world pregnancies, including pregnancies from a large epidemiologic study and published studies over several decades, which found no connection between use of interferon-beta products during early pregnancy and an increased risk of major birth defects, according to the FDA.

As a result, the labels for both medications will no longer have the pregnancy category C designation; however, patients should continue to notify their health care provider if they are pregnant or plan to become pregnant.

The FDA decision to remove the warning follows a similar decision by the European Medicines Agency last year.

“Many women with MS are diagnosed during their childbearing years. With this important update for Plegridy and Avonex, healthcare providers have more data to inform appropriate treatment paths for patients who may be pregnant or planning for pregnancy,” said Bernd Kieseier, MD, MHBA, executive director and head of global MS at Worldwide Medical, Biogen, in a press release.

lfranki@mdedge.com

The Food and Drug Administration has updated the labels for peginterferon beta-1a (Plegridy) and interferon beta-1a (Avonex) to include more information about usage of these medications during pregnancy and breastfeeding in women with multiple sclerosis (MS).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The FDA based the decision on data from more than 1,000 real-world pregnancies, including pregnancies from a large epidemiologic study and published studies over several decades, which found no connection between use of interferon-beta products during early pregnancy and an increased risk of major birth defects, according to the FDA.

As a result, the labels for both medications will no longer have the pregnancy category C designation; however, patients should continue to notify their health care provider if they are pregnant or plan to become pregnant.

The FDA decision to remove the warning follows a similar decision by the European Medicines Agency last year.

“Many women with MS are diagnosed during their childbearing years. With this important update for Plegridy and Avonex, healthcare providers have more data to inform appropriate treatment paths for patients who may be pregnant or planning for pregnancy,” said Bernd Kieseier, MD, MHBA, executive director and head of global MS at Worldwide Medical, Biogen, in a press release.

lfranki@mdedge.com

Neurologists are offering guidance regarding how COVID-19 may affects patients with neurologic disorders, often based on scientific principles and limited evidence from the current pandemic. Neurologic disorders are among the “underlying medical conditions that may increase the risk of serious COVID-19 for individuals of any age,” according to the Centers for Disease Control and Prevention.

Potentially relevant drug interactions, how immunosuppressive medications may influence the risk of COVID-19, and neurologic diseases that may be associated with greater risk are among the questions that experts and groups have addressed.

According to the CDC, neurologic conditions that may heighten the risk of severe COVID-19 include “disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.” Many patients, however, may not have substantially increased risks, neurologists suggest.

“Patients with conditions that do not affect their swallowing or breathing muscles and in whom the immune system is working normally are not considered to be at increased risk from COVID-19,” according to March 26 guidance from the Association of British Neurologists (ABN). “Milder or moderate forms of many of the commoner neurological disorders, such as Parkinson’s disease, multiple sclerosis, epilepsy, are not currently considered to confer increased risk, so long as the breathing and swallowing muscles are functioning well.”

Neurologists should tailor treatment decisions to individual patients, according to the ABN. “Although some neurological conditions or treatments increase the risk of complicated COVID-19, most patients in these groups will overcome the infection,” the association noted.
 

Interactions with potential COVID-19 treatments

Standard drugs in neurology may interact with potential COVID-19 treatments. For example, “preliminary experience suggests that there is a possible benefit from hydroxychloroquine and azithromycin treatment in COVID-19 infection,” but either of those drugs “may lead to a deterioration in myasthenia gravis,” the ABN notes. “Doctors will have to balance the risks from myasthenia and COVID-19 on a case-by-case basis.” The Liverpool Drug Interactions Group has published tables that describe interactions between potential COVID-19 treatments and anticonvulsants, analgesics, immunosuppressants, and other medication classes.

Many muscle diseases and neuromuscular junction diseases may entail higher risks of complicated COVID-19, the ABN suggested. For patients on immunotherapy, the medication may be a more important consideration for COVID-19 than the underlying disease. Other comorbidities such as hypertension, renal impairment, neutropenia, lymphopenia, liver disease, diabetes mellitus, ischemic heart disease, and lung disease may be important factors, according to the association.
 

Seizures may not worsen

After the CDC added epilepsy to its list of conditions that entail higher risk of severe COVID-19, M. Scott Perry, MD, medical director of neurology at Cook Children’s Medical Center in Fort Worth, Tex., commented on Twitter that “most healthy people with controlled epilepsy [are] probably at no more risk than others.”

“Those treated with steroids or other immunosuppressive drugs are likely higher risk,” Dr. Perry said. “Likewise, patients with other medical comorbidities such as muscle weakness, swallowing or breathing problems, and other complex cases of epilepsy are likely higher risk. Regardless: be responsible, avoid crowds, wash your hands, avoid sick contacts.”

Doctors in Italy, based on small numbers of cases, have found that seizures are not worse in patients with epilepsy and COVID-19, said Dr. Perry. A few children, including several patients with Dravet syndrome, “had uncomplicated illness and seizures were no worse,” he said. “That is reassuring.”

“Until now, there is no evidence of a direct effect of COVID-19 on seizures or epilepsy,” according to the International League Against Epilepsy (ILAE). “However, patients may experience worsening of seizures due to systemic illnesses, drug interactions, decreased access to antiseizure medications, and increased stress.”

“In younger children, the fever that accompanies COVID-19 may exacerbate seizures, as might any febrile illness,” according to an American Epilepsy Society (AES) resource for epilepsy clinicians. “The main known elevated risk factors related to COVID-19 are age, respiratory disease, and other chronic medical conditions not related to epilepsy. As for all, people with epilepsy should adhere to the CDC recommendations for reducing risk of infection.” Neurologists should review with patients the importance of treatment adherence, update plans for managing breakthrough seizures, and ensure necessary medications are on hand, according to the AES.

The Epilepsy Foundation created a page with information about COVID-19 for patients with epilepsy and recorded a discussion with epilepsy specialists. DEE-P (Developmental Epileptic Encephalopathy–Project) Connections recorded a webinar about protecting medically complex or immune-suppressed children with epilepsy from COVID-19.

MS DMTs and the coronavirus

The National Multiple Sclerosis (MS) Society has provided guidance on the use of disease-modifying therapies (DMTs) during the COVID-19 pandemic. “There are numerous recommendations circulating that attempt to provide clarity and guidance, however, differences among the recommendations have created confusion,” the society says. “DMT decision making varies significantly from country to country, ranging from highly provider-directed to a collaborative decision-making model. ... DMT decisions should be individualized and made collaboratively between the person with MS and his/her healthcare provider.”

Patients with MS and their physicians should weigh risks and benefits before starting cell-depleting DMTs such as alemtuzumab, cladribine, ocrelizumab, or rituximab, according the National MS Society. They also should consider the risks and benefits of DMTs that carry warnings of a potentially severe increase in disability after stopping therapy, such as fingolimod and natalizumab. “We endorse the global advice provided by the MS International Federation (MSIF) – but emphasize that DMT decision making must be individualized and based upon multiple factors,” the National MS Society said.

Neurologists currently lack evidence about how COVID-19 affects patients with MS, according to the MSIF, which based its DMT guidance on advice from MS neurologists and research experts from member organizations. Many DMTs suppress or modify the immune system, and “some MS medications might increase the likelihood of developing complications from a COVID-19 infection but this risk needs to be balanced with the risks of stopping treatment,” according to the federation.

Patients currently taking DMTs should continue treatment, and those who develop symptoms of COVID-19 or test positive for the infection should discuss their DMT with a health care professional familiar with their care, the MSIF recommends. Decisions about starting a DMT should take into account a patient’s disease course, disease activity, and regional COVID-19 risks, according to the federation. For patients due to start DMT, treatments that do not reduce lymphocytes, such as interferons, glatiramer acetate, or natalizumab, should be considered.

Fingolimod, dimethyl fumarate, teriflunomide, and siponimod “may reduce the ability of the immune system to respond to an infection,” and “people should carefully consider the risks and benefits of initiating these treatments during the COVID-19 pandemic,” according to the federation. “People with MS who are currently taking alemtuzumab, cladribine, ocrelizumab, rituximab, fingolimod, dimethyl fumarate, teriflunomide or siponimod and are living in a community with a COVID-19 outbreak should isolate as much as possible to reduce their risk of infection.”

Extended isolation during the COVID-19 outbreak may be warranted for patients with MS who have recently undergone autologous hematopoietic stem cell treatment, which entails intensive chemotherapy, the guidance says. In addition, postponement of this procedure should be considered.

Child neurology, migraine, movement disorders, and stroke

The Child Neurology Foundation (CNF) and Child Neurology Society (CNS) published a joint statement about COVID-19. “Most children who contract COVID-19 appear to exhibit only mild symptoms,” said Scott Pomeroy, MD, president of CNF’s board of directors and chair of the department of neurology at Boston Children’s Hospital, in the statement. “However, if your child is taking a medication such as steroids that can lower their immune system response, there could be an increased risk for more significant symptoms. In addition, children with lung disease, such as asthma, may also be at higher risk. Therefore, it is important to practice preventative precautions. We hope that this information will help to reduce some of the fears that families in our community may be experiencing.”

The American Migraine Foundation shared COVID-19 considerations for patients with migraine from Mia Minen, MD, associate professor of neurology and population health at NYU Langone in New York. Patients with migraine who are otherwise in good health are not expected to be at increased risk of severe COVID-19, according to Dr. Minen. Best practices include having an adequate supply of medicine, considering alternatives to in-person doctor visits, and being “mindful of routine and diet to reduce migraine triggers,” the foundation suggests. In addition, patients should try to limit stress and seek out “alternative methods of social interaction.”

“The relationship between COVID-19 and Parkinson’s disease or other movement disorders remains unknown,” the International Parkinson and Movement Disorder Society said. “In general, we recommend that our movement disorder patients do not assume they are at extreme risks, which for the time being are uncertain. Nevertheless, we strongly recommend following the standard measures strictly to avoid exposures to the virus.”

The American Heart Association (AHA) cautions that older patients with coronary heart disease or hypertension “may be more likely than others to be infected by the coronavirus that causes COVID-19 and to develop more severe symptoms.” In addition, people with a history of stroke “may face a higher risk of complications,” according to the AHA. “As a result, people who have heart disease or another underlying condition should stay home to limit their risk of contracting the virus.”

Several groups emphasized the importance of telemedicine as an option for patients with neurologic conditions during the pandemic. The American Headache Society has hosted discussions on conducting neurologic exams via telemedicine. The American Academy of Neurology also conducted a webinar on telemedicine and COVID-19 and created a page with COVID-19 resources. The journal Neurology is publishing invited commentaries about neurologic aspects of the COVID-19 pandemic.

jremaly@mdedge.com

Neurologists are offering guidance regarding how COVID-19 may affects patients with neurologic disorders, often based on scientific principles and limited evidence from the current pandemic. Neurologic disorders are among the “underlying medical conditions that may increase the risk of serious COVID-19 for individuals of any age,” according to the Centers for Disease Control and Prevention.

Potentially relevant drug interactions, how immunosuppressive medications may influence the risk of COVID-19, and neurologic diseases that may be associated with greater risk are among the questions that experts and groups have addressed.

According to the CDC, neurologic conditions that may heighten the risk of severe COVID-19 include “disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.” Many patients, however, may not have substantially increased risks, neurologists suggest.

“Patients with conditions that do not affect their swallowing or breathing muscles and in whom the immune system is working normally are not considered to be at increased risk from COVID-19,” according to March 26 guidance from the Association of British Neurologists (ABN). “Milder or moderate forms of many of the commoner neurological disorders, such as Parkinson’s disease, multiple sclerosis, epilepsy, are not currently considered to confer increased risk, so long as the breathing and swallowing muscles are functioning well.”

Neurologists should tailor treatment decisions to individual patients, according to the ABN. “Although some neurological conditions or treatments increase the risk of complicated COVID-19, most patients in these groups will overcome the infection,” the association noted.
 

Interactions with potential COVID-19 treatments

Standard drugs in neurology may interact with potential COVID-19 treatments. For example, “preliminary experience suggests that there is a possible benefit from hydroxychloroquine and azithromycin treatment in COVID-19 infection,” but either of those drugs “may lead to a deterioration in myasthenia gravis,” the ABN notes. “Doctors will have to balance the risks from myasthenia and COVID-19 on a case-by-case basis.” The Liverpool Drug Interactions Group has published tables that describe interactions between potential COVID-19 treatments and anticonvulsants, analgesics, immunosuppressants, and other medication classes.

Many muscle diseases and neuromuscular junction diseases may entail higher risks of complicated COVID-19, the ABN suggested. For patients on immunotherapy, the medication may be a more important consideration for COVID-19 than the underlying disease. Other comorbidities such as hypertension, renal impairment, neutropenia, lymphopenia, liver disease, diabetes mellitus, ischemic heart disease, and lung disease may be important factors, according to the association.
 

Seizures may not worsen

After the CDC added epilepsy to its list of conditions that entail higher risk of severe COVID-19, M. Scott Perry, MD, medical director of neurology at Cook Children’s Medical Center in Fort Worth, Tex., commented on Twitter that “most healthy people with controlled epilepsy [are] probably at no more risk than others.”

“Those treated with steroids or other immunosuppressive drugs are likely higher risk,” Dr. Perry said. “Likewise, patients with other medical comorbidities such as muscle weakness, swallowing or breathing problems, and other complex cases of epilepsy are likely higher risk. Regardless: be responsible, avoid crowds, wash your hands, avoid sick contacts.”

Doctors in Italy, based on small numbers of cases, have found that seizures are not worse in patients with epilepsy and COVID-19, said Dr. Perry. A few children, including several patients with Dravet syndrome, “had uncomplicated illness and seizures were no worse,” he said. “That is reassuring.”

“Until now, there is no evidence of a direct effect of COVID-19 on seizures or epilepsy,” according to the International League Against Epilepsy (ILAE). “However, patients may experience worsening of seizures due to systemic illnesses, drug interactions, decreased access to antiseizure medications, and increased stress.”

“In younger children, the fever that accompanies COVID-19 may exacerbate seizures, as might any febrile illness,” according to an American Epilepsy Society (AES) resource for epilepsy clinicians. “The main known elevated risk factors related to COVID-19 are age, respiratory disease, and other chronic medical conditions not related to epilepsy. As for all, people with epilepsy should adhere to the CDC recommendations for reducing risk of infection.” Neurologists should review with patients the importance of treatment adherence, update plans for managing breakthrough seizures, and ensure necessary medications are on hand, according to the AES.

The Epilepsy Foundation created a page with information about COVID-19 for patients with epilepsy and recorded a discussion with epilepsy specialists. DEE-P (Developmental Epileptic Encephalopathy–Project) Connections recorded a webinar about protecting medically complex or immune-suppressed children with epilepsy from COVID-19.

MS DMTs and the coronavirus

The National Multiple Sclerosis (MS) Society has provided guidance on the use of disease-modifying therapies (DMTs) during the COVID-19 pandemic. “There are numerous recommendations circulating that attempt to provide clarity and guidance, however, differences among the recommendations have created confusion,” the society says. “DMT decision making varies significantly from country to country, ranging from highly provider-directed to a collaborative decision-making model. ... DMT decisions should be individualized and made collaboratively between the person with MS and his/her healthcare provider.”

Patients with MS and their physicians should weigh risks and benefits before starting cell-depleting DMTs such as alemtuzumab, cladribine, ocrelizumab, or rituximab, according the National MS Society. They also should consider the risks and benefits of DMTs that carry warnings of a potentially severe increase in disability after stopping therapy, such as fingolimod and natalizumab. “We endorse the global advice provided by the MS International Federation (MSIF) – but emphasize that DMT decision making must be individualized and based upon multiple factors,” the National MS Society said.

Neurologists currently lack evidence about how COVID-19 affects patients with MS, according to the MSIF, which based its DMT guidance on advice from MS neurologists and research experts from member organizations. Many DMTs suppress or modify the immune system, and “some MS medications might increase the likelihood of developing complications from a COVID-19 infection but this risk needs to be balanced with the risks of stopping treatment,” according to the federation.

Patients currently taking DMTs should continue treatment, and those who develop symptoms of COVID-19 or test positive for the infection should discuss their DMT with a health care professional familiar with their care, the MSIF recommends. Decisions about starting a DMT should take into account a patient’s disease course, disease activity, and regional COVID-19 risks, according to the federation. For patients due to start DMT, treatments that do not reduce lymphocytes, such as interferons, glatiramer acetate, or natalizumab, should be considered.

Fingolimod, dimethyl fumarate, teriflunomide, and siponimod “may reduce the ability of the immune system to respond to an infection,” and “people should carefully consider the risks and benefits of initiating these treatments during the COVID-19 pandemic,” according to the federation. “People with MS who are currently taking alemtuzumab, cladribine, ocrelizumab, rituximab, fingolimod, dimethyl fumarate, teriflunomide or siponimod and are living in a community with a COVID-19 outbreak should isolate as much as possible to reduce their risk of infection.”

Extended isolation during the COVID-19 outbreak may be warranted for patients with MS who have recently undergone autologous hematopoietic stem cell treatment, which entails intensive chemotherapy, the guidance says. In addition, postponement of this procedure should be considered.

Child neurology, migraine, movement disorders, and stroke

The Child Neurology Foundation (CNF) and Child Neurology Society (CNS) published a joint statement about COVID-19. “Most children who contract COVID-19 appear to exhibit only mild symptoms,” said Scott Pomeroy, MD, president of CNF’s board of directors and chair of the department of neurology at Boston Children’s Hospital, in the statement. “However, if your child is taking a medication such as steroids that can lower their immune system response, there could be an increased risk for more significant symptoms. In addition, children with lung disease, such as asthma, may also be at higher risk. Therefore, it is important to practice preventative precautions. We hope that this information will help to reduce some of the fears that families in our community may be experiencing.”

The American Migraine Foundation shared COVID-19 considerations for patients with migraine from Mia Minen, MD, associate professor of neurology and population health at NYU Langone in New York. Patients with migraine who are otherwise in good health are not expected to be at increased risk of severe COVID-19, according to Dr. Minen. Best practices include having an adequate supply of medicine, considering alternatives to in-person doctor visits, and being “mindful of routine and diet to reduce migraine triggers,” the foundation suggests. In addition, patients should try to limit stress and seek out “alternative methods of social interaction.”

“The relationship between COVID-19 and Parkinson’s disease or other movement disorders remains unknown,” the International Parkinson and Movement Disorder Society said. “In general, we recommend that our movement disorder patients do not assume they are at extreme risks, which for the time being are uncertain. Nevertheless, we strongly recommend following the standard measures strictly to avoid exposures to the virus.”

The American Heart Association (AHA) cautions that older patients with coronary heart disease or hypertension “may be more likely than others to be infected by the coronavirus that causes COVID-19 and to develop more severe symptoms.” In addition, people with a history of stroke “may face a higher risk of complications,” according to the AHA. “As a result, people who have heart disease or another underlying condition should stay home to limit their risk of contracting the virus.”

Several groups emphasized the importance of telemedicine as an option for patients with neurologic conditions during the pandemic. The American Headache Society has hosted discussions on conducting neurologic exams via telemedicine. The American Academy of Neurology also conducted a webinar on telemedicine and COVID-19 and created a page with COVID-19 resources. The journal Neurology is publishing invited commentaries about neurologic aspects of the COVID-19 pandemic.

jremaly@mdedge.com

Neurologists are offering guidance regarding how COVID-19 may affects patients with neurologic disorders, often based on scientific principles and limited evidence from the current pandemic. Neurologic disorders are among the “underlying medical conditions that may increase the risk of serious COVID-19 for individuals of any age,” according to the Centers for Disease Control and Prevention.

Potentially relevant drug interactions, how immunosuppressive medications may influence the risk of COVID-19, and neurologic diseases that may be associated with greater risk are among the questions that experts and groups have addressed.

According to the CDC, neurologic conditions that may heighten the risk of severe COVID-19 include “disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.” Many patients, however, may not have substantially increased risks, neurologists suggest.

“Patients with conditions that do not affect their swallowing or breathing muscles and in whom the immune system is working normally are not considered to be at increased risk from COVID-19,” according to March 26 guidance from the Association of British Neurologists (ABN). “Milder or moderate forms of many of the commoner neurological disorders, such as Parkinson’s disease, multiple sclerosis, epilepsy, are not currently considered to confer increased risk, so long as the breathing and swallowing muscles are functioning well.”

Neurologists should tailor treatment decisions to individual patients, according to the ABN. “Although some neurological conditions or treatments increase the risk of complicated COVID-19, most patients in these groups will overcome the infection,” the association noted.
 

Interactions with potential COVID-19 treatments

Standard drugs in neurology may interact with potential COVID-19 treatments. For example, “preliminary experience suggests that there is a possible benefit from hydroxychloroquine and azithromycin treatment in COVID-19 infection,” but either of those drugs “may lead to a deterioration in myasthenia gravis,” the ABN notes. “Doctors will have to balance the risks from myasthenia and COVID-19 on a case-by-case basis.” The Liverpool Drug Interactions Group has published tables that describe interactions between potential COVID-19 treatments and anticonvulsants, analgesics, immunosuppressants, and other medication classes.

Many muscle diseases and neuromuscular junction diseases may entail higher risks of complicated COVID-19, the ABN suggested. For patients on immunotherapy, the medication may be a more important consideration for COVID-19 than the underlying disease. Other comorbidities such as hypertension, renal impairment, neutropenia, lymphopenia, liver disease, diabetes mellitus, ischemic heart disease, and lung disease may be important factors, according to the association.
 

Seizures may not worsen

After the CDC added epilepsy to its list of conditions that entail higher risk of severe COVID-19, M. Scott Perry, MD, medical director of neurology at Cook Children’s Medical Center in Fort Worth, Tex., commented on Twitter that “most healthy people with controlled epilepsy [are] probably at no more risk than others.”

“Those treated with steroids or other immunosuppressive drugs are likely higher risk,” Dr. Perry said. “Likewise, patients with other medical comorbidities such as muscle weakness, swallowing or breathing problems, and other complex cases of epilepsy are likely higher risk. Regardless: be responsible, avoid crowds, wash your hands, avoid sick contacts.”

Doctors in Italy, based on small numbers of cases, have found that seizures are not worse in patients with epilepsy and COVID-19, said Dr. Perry. A few children, including several patients with Dravet syndrome, “had uncomplicated illness and seizures were no worse,” he said. “That is reassuring.”

“Until now, there is no evidence of a direct effect of COVID-19 on seizures or epilepsy,” according to the International League Against Epilepsy (ILAE). “However, patients may experience worsening of seizures due to systemic illnesses, drug interactions, decreased access to antiseizure medications, and increased stress.”

“In younger children, the fever that accompanies COVID-19 may exacerbate seizures, as might any febrile illness,” according to an American Epilepsy Society (AES) resource for epilepsy clinicians. “The main known elevated risk factors related to COVID-19 are age, respiratory disease, and other chronic medical conditions not related to epilepsy. As for all, people with epilepsy should adhere to the CDC recommendations for reducing risk of infection.” Neurologists should review with patients the importance of treatment adherence, update plans for managing breakthrough seizures, and ensure necessary medications are on hand, according to the AES.

The Epilepsy Foundation created a page with information about COVID-19 for patients with epilepsy and recorded a discussion with epilepsy specialists. DEE-P (Developmental Epileptic Encephalopathy–Project) Connections recorded a webinar about protecting medically complex or immune-suppressed children with epilepsy from COVID-19.

MS DMTs and the coronavirus

The National Multiple Sclerosis (MS) Society has provided guidance on the use of disease-modifying therapies (DMTs) during the COVID-19 pandemic. “There are numerous recommendations circulating that attempt to provide clarity and guidance, however, differences among the recommendations have created confusion,” the society says. “DMT decision making varies significantly from country to country, ranging from highly provider-directed to a collaborative decision-making model. ... DMT decisions should be individualized and made collaboratively between the person with MS and his/her healthcare provider.”

Patients with MS and their physicians should weigh risks and benefits before starting cell-depleting DMTs such as alemtuzumab, cladribine, ocrelizumab, or rituximab, according the National MS Society. They also should consider the risks and benefits of DMTs that carry warnings of a potentially severe increase in disability after stopping therapy, such as fingolimod and natalizumab. “We endorse the global advice provided by the MS International Federation (MSIF) – but emphasize that DMT decision making must be individualized and based upon multiple factors,” the National MS Society said.

Neurologists currently lack evidence about how COVID-19 affects patients with MS, according to the MSIF, which based its DMT guidance on advice from MS neurologists and research experts from member organizations. Many DMTs suppress or modify the immune system, and “some MS medications might increase the likelihood of developing complications from a COVID-19 infection but this risk needs to be balanced with the risks of stopping treatment,” according to the federation.

Patients currently taking DMTs should continue treatment, and those who develop symptoms of COVID-19 or test positive for the infection should discuss their DMT with a health care professional familiar with their care, the MSIF recommends. Decisions about starting a DMT should take into account a patient’s disease course, disease activity, and regional COVID-19 risks, according to the federation. For patients due to start DMT, treatments that do not reduce lymphocytes, such as interferons, glatiramer acetate, or natalizumab, should be considered.

Fingolimod, dimethyl fumarate, teriflunomide, and siponimod “may reduce the ability of the immune system to respond to an infection,” and “people should carefully consider the risks and benefits of initiating these treatments during the COVID-19 pandemic,” according to the federation. “People with MS who are currently taking alemtuzumab, cladribine, ocrelizumab, rituximab, fingolimod, dimethyl fumarate, teriflunomide or siponimod and are living in a community with a COVID-19 outbreak should isolate as much as possible to reduce their risk of infection.”

Extended isolation during the COVID-19 outbreak may be warranted for patients with MS who have recently undergone autologous hematopoietic stem cell treatment, which entails intensive chemotherapy, the guidance says. In addition, postponement of this procedure should be considered.

Child neurology, migraine, movement disorders, and stroke

The Child Neurology Foundation (CNF) and Child Neurology Society (CNS) published a joint statement about COVID-19. “Most children who contract COVID-19 appear to exhibit only mild symptoms,” said Scott Pomeroy, MD, president of CNF’s board of directors and chair of the department of neurology at Boston Children’s Hospital, in the statement. “However, if your child is taking a medication such as steroids that can lower their immune system response, there could be an increased risk for more significant symptoms. In addition, children with lung disease, such as asthma, may also be at higher risk. Therefore, it is important to practice preventative precautions. We hope that this information will help to reduce some of the fears that families in our community may be experiencing.”

The American Migraine Foundation shared COVID-19 considerations for patients with migraine from Mia Minen, MD, associate professor of neurology and population health at NYU Langone in New York. Patients with migraine who are otherwise in good health are not expected to be at increased risk of severe COVID-19, according to Dr. Minen. Best practices include having an adequate supply of medicine, considering alternatives to in-person doctor visits, and being “mindful of routine and diet to reduce migraine triggers,” the foundation suggests. In addition, patients should try to limit stress and seek out “alternative methods of social interaction.”

“The relationship between COVID-19 and Parkinson’s disease or other movement disorders remains unknown,” the International Parkinson and Movement Disorder Society said. “In general, we recommend that our movement disorder patients do not assume they are at extreme risks, which for the time being are uncertain. Nevertheless, we strongly recommend following the standard measures strictly to avoid exposures to the virus.”

The American Heart Association (AHA) cautions that older patients with coronary heart disease or hypertension “may be more likely than others to be infected by the coronavirus that causes COVID-19 and to develop more severe symptoms.” In addition, people with a history of stroke “may face a higher risk of complications,” according to the AHA. “As a result, people who have heart disease or another underlying condition should stay home to limit their risk of contracting the virus.”

Several groups emphasized the importance of telemedicine as an option for patients with neurologic conditions during the pandemic. The American Headache Society has hosted discussions on conducting neurologic exams via telemedicine. The American Academy of Neurology also conducted a webinar on telemedicine and COVID-19 and created a page with COVID-19 resources. The journal Neurology is publishing invited commentaries about neurologic aspects of the COVID-19 pandemic.

jremaly@mdedge.com

Older adults exposed to air pollution long term – even at fairly low levels – have an increased risk of dementia, and cardiovascular disease (CVD) appears to both modify and mediate this association, according to the results of the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) study.

Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.

In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).

The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.

Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.

Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m³ in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m³ in nitrogen oxide during that time period.

Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.

In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).

Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.

The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.

Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.

SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
 

Older adults exposed to air pollution long term – even at fairly low levels – have an increased risk of dementia, and cardiovascular disease (CVD) appears to both modify and mediate this association, according to the results of the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) study.

Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.

In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).

The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.

Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.

Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m³ in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m³ in nitrogen oxide during that time period.

Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.

In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).

Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.

The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.

Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.

SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
 

Older adults exposed to air pollution long term – even at fairly low levels – have an increased risk of dementia, and cardiovascular disease (CVD) appears to both modify and mediate this association, according to the results of the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) study.

Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.

In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).

The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.

Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.

Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m³ in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m³ in nitrogen oxide during that time period.

Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.

In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).

Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.

The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.

Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.

SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
 

In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals. The ubiquity and remarkable technological progress of personal computing devices, including wearables, smartphones, and tablets, along with the multitude of sensor modalities embedded within these devices, enables a continuous connection with individuals wanting to share information about their behavior and daily life.

Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
 

Identifying a disease early

One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.

In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.¹

Courtesy of Evidation Health, Inc.

A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
 

Leading to better health outcomes

The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.²

This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.

Presenting new challenges

While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.³

Cortesy of Evidation Health

The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.

This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.

Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.⁴ With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events.  Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.⁵ This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.

Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.

Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.

References

1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.

2. The Heartline Study. https://www.heartline.com.

3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.

4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.

5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.

In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals. The ubiquity and remarkable technological progress of personal computing devices, including wearables, smartphones, and tablets, along with the multitude of sensor modalities embedded within these devices, enables a continuous connection with individuals wanting to share information about their behavior and daily life.

Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
 

Identifying a disease early

One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.

In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.¹

Courtesy of Evidation Health, Inc.

A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
 

Leading to better health outcomes

The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.²

This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.

Presenting new challenges

While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.³

Cortesy of Evidation Health

The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.

This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.

Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.⁴ With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events.  Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.⁵ This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.

Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.

Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.

References

1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.

2. The Heartline Study. https://www.heartline.com.

3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.

4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.

5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.

In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals. The ubiquity and remarkable technological progress of personal computing devices, including wearables, smartphones, and tablets, along with the multitude of sensor modalities embedded within these devices, enables a continuous connection with individuals wanting to share information about their behavior and daily life.

Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
 

Identifying a disease early

One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.

In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.¹

Courtesy of Evidation Health, Inc.

A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
 

Leading to better health outcomes

The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.²

This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.

Presenting new challenges

While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.³

Cortesy of Evidation Health

The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.

This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.

Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.⁴ With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events.  Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.⁵ This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.

Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.

Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.

References

1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.

2. The Heartline Study. https://www.heartline.com.

3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.

4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.

5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.

Differences in metabolism of levodopa between patients with Parkinson’s disease may be caused by variations in gut bacteria, according to investigators.

Specifically, patients with a higher abundance of Enterococcus faecalis may be converting levodopa into dopamine via decarboxylation before it can cross the blood-brain barrier, reported Emily P. Balskus, PhD, of Harvard University in Cambridge, Mass.

Although existing decarboxylase inhibitors, such as carbidopa, can reduce metabolism of levodopa by host enzymes, these drugs are unable to inhibit the enzymatic activity of E. faecalis in the gut, Dr. Balskus said at the annual Gut Microbiota for Health World Summit, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

“[Carbidopa] is actually completely ineffective at inhibiting decarboxylation in human fecal suspension,” Dr. Balskus said, referring to research led by PhD student Vayu Maini Rekdal. “We think that this could indicate that patients who are taking carbidopa are not inhibiting any bacterial metabolism that they may have.”

While previous research showed that E. faecalis could decarboxylate levodopa, Dr. Balskus and colleagues linked this process with the tyrosine decarboxylase gene (TyrDC), and showed that the of abundance E. faecalis and TyrDC correlate with levodopa metabolism.

Unlike the human enzyme responsible for decarboxylation of levodopa, the E. faecalis enzyme preferentially binds with L-tyrosine. This could explain why existing decarboxylase inhibitors have little impact on decarboxylation in the gut, Dr. Balskus said.

She also noted that this unique characteristic may open doors to new therapeutics. In the lab, Dr. Balskus and colleagues tested a decarboxylase inhibitor that resembled L-tyrosine, (S)-alpha-fluoromethyltyrosine (AFMT). Indeed, AFMT completely inhibited of decarboxylation of levodopa in both E. faecalis cells and complex human microbiome samples.

“We think this is pretty exciting,” Dr. Balskus said.

Early animal studies support this enthusiasm, as germ-free mice colonized with E. faecalis maintain higher serum levels of levodopa with concurrent administration of AFMT.

“We think that this could indicate that a promising way to improve levodopa therapy for Parkinson’s patients would be to develop compounds that inhibit bacterial drug metabolism activity,” Dr. Balskus said.

Concluding her presentation, Dr. Balskus emphasized the importance of a biochemical approach to microbiome research. “Studying enzymes opens up new, exciting opportunities for microbiome manipulation. We can design or develop inhibitors of enzymes, use those inhibitors as tools to study the roles of individual metabolic activities, and potentially use them as therapeutics. We are very excited about the possibility of treating or preventing human disease not just by manipulating processes in our own cells, but by targeting activities in the microbiota.”

Dr. Balskus reported funding from HHMI, the Bill and Melinda Gates Foundation, the David and Lucile Packard Foundation, and Merck.

Differences in metabolism of levodopa between patients with Parkinson’s disease may be caused by variations in gut bacteria, according to investigators.

Specifically, patients with a higher abundance of Enterococcus faecalis may be converting levodopa into dopamine via decarboxylation before it can cross the blood-brain barrier, reported Emily P. Balskus, PhD, of Harvard University in Cambridge, Mass.

Although existing decarboxylase inhibitors, such as carbidopa, can reduce metabolism of levodopa by host enzymes, these drugs are unable to inhibit the enzymatic activity of E. faecalis in the gut, Dr. Balskus said at the annual Gut Microbiota for Health World Summit, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

“[Carbidopa] is actually completely ineffective at inhibiting decarboxylation in human fecal suspension,” Dr. Balskus said, referring to research led by PhD student Vayu Maini Rekdal. “We think that this could indicate that patients who are taking carbidopa are not inhibiting any bacterial metabolism that they may have.”

While previous research showed that E. faecalis could decarboxylate levodopa, Dr. Balskus and colleagues linked this process with the tyrosine decarboxylase gene (TyrDC), and showed that the of abundance E. faecalis and TyrDC correlate with levodopa metabolism.

Unlike the human enzyme responsible for decarboxylation of levodopa, the E. faecalis enzyme preferentially binds with L-tyrosine. This could explain why existing decarboxylase inhibitors have little impact on decarboxylation in the gut, Dr. Balskus said.

She also noted that this unique characteristic may open doors to new therapeutics. In the lab, Dr. Balskus and colleagues tested a decarboxylase inhibitor that resembled L-tyrosine, (S)-alpha-fluoromethyltyrosine (AFMT). Indeed, AFMT completely inhibited of decarboxylation of levodopa in both E. faecalis cells and complex human microbiome samples.

“We think this is pretty exciting,” Dr. Balskus said.

Early animal studies support this enthusiasm, as germ-free mice colonized with E. faecalis maintain higher serum levels of levodopa with concurrent administration of AFMT.

“We think that this could indicate that a promising way to improve levodopa therapy for Parkinson’s patients would be to develop compounds that inhibit bacterial drug metabolism activity,” Dr. Balskus said.

Concluding her presentation, Dr. Balskus emphasized the importance of a biochemical approach to microbiome research. “Studying enzymes opens up new, exciting opportunities for microbiome manipulation. We can design or develop inhibitors of enzymes, use those inhibitors as tools to study the roles of individual metabolic activities, and potentially use them as therapeutics. We are very excited about the possibility of treating or preventing human disease not just by manipulating processes in our own cells, but by targeting activities in the microbiota.”

Dr. Balskus reported funding from HHMI, the Bill and Melinda Gates Foundation, the David and Lucile Packard Foundation, and Merck.

Differences in metabolism of levodopa between patients with Parkinson’s disease may be caused by variations in gut bacteria, according to investigators.

Specifically, patients with a higher abundance of Enterococcus faecalis may be converting levodopa into dopamine via decarboxylation before it can cross the blood-brain barrier, reported Emily P. Balskus, PhD, of Harvard University in Cambridge, Mass.

Although existing decarboxylase inhibitors, such as carbidopa, can reduce metabolism of levodopa by host enzymes, these drugs are unable to inhibit the enzymatic activity of E. faecalis in the gut, Dr. Balskus said at the annual Gut Microbiota for Health World Summit, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

“[Carbidopa] is actually completely ineffective at inhibiting decarboxylation in human fecal suspension,” Dr. Balskus said, referring to research led by PhD student Vayu Maini Rekdal. “We think that this could indicate that patients who are taking carbidopa are not inhibiting any bacterial metabolism that they may have.”

While previous research showed that E. faecalis could decarboxylate levodopa, Dr. Balskus and colleagues linked this process with the tyrosine decarboxylase gene (TyrDC), and showed that the of abundance E. faecalis and TyrDC correlate with levodopa metabolism.

Unlike the human enzyme responsible for decarboxylation of levodopa, the E. faecalis enzyme preferentially binds with L-tyrosine. This could explain why existing decarboxylase inhibitors have little impact on decarboxylation in the gut, Dr. Balskus said.

She also noted that this unique characteristic may open doors to new therapeutics. In the lab, Dr. Balskus and colleagues tested a decarboxylase inhibitor that resembled L-tyrosine, (S)-alpha-fluoromethyltyrosine (AFMT). Indeed, AFMT completely inhibited of decarboxylation of levodopa in both E. faecalis cells and complex human microbiome samples.

“We think this is pretty exciting,” Dr. Balskus said.

Early animal studies support this enthusiasm, as germ-free mice colonized with E. faecalis maintain higher serum levels of levodopa with concurrent administration of AFMT.

“We think that this could indicate that a promising way to improve levodopa therapy for Parkinson’s patients would be to develop compounds that inhibit bacterial drug metabolism activity,” Dr. Balskus said.

Concluding her presentation, Dr. Balskus emphasized the importance of a biochemical approach to microbiome research. “Studying enzymes opens up new, exciting opportunities for microbiome manipulation. We can design or develop inhibitors of enzymes, use those inhibitors as tools to study the roles of individual metabolic activities, and potentially use them as therapeutics. We are very excited about the possibility of treating or preventing human disease not just by manipulating processes in our own cells, but by targeting activities in the microbiota.”

Dr. Balskus reported funding from HHMI, the Bill and Melinda Gates Foundation, the David and Lucile Packard Foundation, and Merck.