Neurology

Reference

1. US Preventive Services Task Force. Final recommendation statement: cognitive impairment in older adults: screening. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/cognitive-impairment-in-older-adults-screening. Published February 2020. Accessed March 19, 2020.

Reference

1. US Preventive Services Task Force. Final recommendation statement: cognitive impairment in older adults: screening. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/cognitive-impairment-in-older-adults-screening. Published February 2020. Accessed March 19, 2020.

Reference

1. US Preventive Services Task Force. Final recommendation statement: cognitive impairment in older adults: screening. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/cognitive-impairment-in-older-adults-screening. Published February 2020. Accessed March 19, 2020.

LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.

Mitchel L. Zoler/MDedge News

In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.

“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.

The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.

During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.

The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.

[email protected]

SOURCE: Waziry R et al. ISC 2020, Abstract LB14.

LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.

Mitchel L. Zoler/MDedge News

In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.

“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.

The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.

During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.

The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.

[email protected]

SOURCE: Waziry R et al. ISC 2020, Abstract LB14.

LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.

Mitchel L. Zoler/MDedge News

In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.

“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.

The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.

During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.

The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.

[email protected]

SOURCE: Waziry R et al. ISC 2020, Abstract LB14.

The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.

The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.

According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:

• Obtain a baseline severity score.
• Identify etiology as spontaneous or treatment related.
• Perform coagulopathy reversal or anticoagulant reversal.
• Administer venous thromboembolism prophylaxis.
• Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
• Provide patient management in a multidisciplinary stroke or ICU unit.
• Prescribe appropriate blood pressure treatment at discharge.
• Perform assessment for rehabilitation.
• Avoid prescribing corticosteroids and other contraindicated drugs.

GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.

The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”

[email protected]

The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.

The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.

According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:

• Obtain a baseline severity score.
• Identify etiology as spontaneous or treatment related.
• Perform coagulopathy reversal or anticoagulant reversal.
• Administer venous thromboembolism prophylaxis.
• Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
• Provide patient management in a multidisciplinary stroke or ICU unit.
• Prescribe appropriate blood pressure treatment at discharge.
• Perform assessment for rehabilitation.
• Avoid prescribing corticosteroids and other contraindicated drugs.

GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.

The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”

[email protected]

The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.

The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.

According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:

• Obtain a baseline severity score.
• Identify etiology as spontaneous or treatment related.
• Perform coagulopathy reversal or anticoagulant reversal.
• Administer venous thromboembolism prophylaxis.
• Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
• Provide patient management in a multidisciplinary stroke or ICU unit.
• Prescribe appropriate blood pressure treatment at discharge.
• Perform assessment for rehabilitation.
• Avoid prescribing corticosteroids and other contraindicated drugs.

GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.

The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”

[email protected]

LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.

“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.

The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.

“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
 

MISTIE III showcases better ICH outcomes

Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.

However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.

The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.

When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.

“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.

She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
 

A message for acute-care clinicians

She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.

“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.

In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.

Mitchel L. Zoler/MDedge News

“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.

“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.

An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
 

More evidence needed to prove MISTIE’s hypothesis

According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.

Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.

Mitchel L. Zoler/MDedge News

Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.

But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.

“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.

Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.

[email protected]

LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.

“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.

The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.

“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
 

MISTIE III showcases better ICH outcomes

Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.

However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.

The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.

When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.

“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.

She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
 

A message for acute-care clinicians

She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.

“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.

In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.

Mitchel L. Zoler/MDedge News

“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.

“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.

An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
 

More evidence needed to prove MISTIE’s hypothesis

According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.

Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.

Mitchel L. Zoler/MDedge News

Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.

But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.

“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.

Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.

[email protected]

LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.

“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.

The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.

“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
 

MISTIE III showcases better ICH outcomes

Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.

However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.

The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.

When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.

“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.

She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
 

A message for acute-care clinicians

She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.

“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.

In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.

Mitchel L. Zoler/MDedge News

“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.

“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.

An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
 

More evidence needed to prove MISTIE’s hypothesis

According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.

Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.

Mitchel L. Zoler/MDedge News

Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.

But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.

“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.

Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.

[email protected]

Urgent care centers may not use optimal medications for the management of acute migraine attacks, according to a study published in the March issue of Headache. Pain and nausea or vomiting associated with migraine may go undertreated, and treatment may not be consistent with American Headache Society (AHS) guidelines for EDs, said Mia T. Minen, MD, of the department of neurology and population health at NYU Langone Health in New York and colleagues.

“Our study findings raise the question as to whether the patients with migraine in the urgent care setting should be managed similarly to the ED, and whether the AHS guidelines for the ED should be revisited and applied to urgent care,” the researchers noted.

Relative to the ED, urgent care centers may provide cost savings and emerge “as a preferred place for treatment for people with migraine, perhaps as they are potentially more quiet medical settings where people with migraine might expeditiously receive care,” the authors said.

Dr. Minen and colleagues conducted a retrospective chart review to assess migraine management at two urgent care centers in New York. They examined the number of urgent care visits for migraine, treatments used, and how closely clinicians followed the AHS recommendations for administration of antiemetic medication and triptans, among other outcomes.

The study population included adults diagnosed with migraine at the NYU Langone Medhattan Urgent Care center between Dec. 1, 2015, and Dec. 1, 2018, or at the NYU Langone Ambulatory Care Urgent Care West Side center between May 1, 2017, and Dec. 1, 2018. Of more than 32,000 urgent care visits during the study period, 78 patients received a migraine diagnosis. Patients with migraine had an average age of 32.5 years, and 79.5% were female. More than half had a documented history of migraine. Two of the patients (2.6%) had been to an emergency department for headache or migraine.

Less than half of the patients who presented with pain (46.6%) were given medication, most commonly ketorolac injection. Most patients (78.2%) received prescriptions, and 25.6% received a triptan prescription. About 60% of patients were told to follow up with a neurologist. In addition, 11.5% revisited urgent care with a migraine or headache or to request a prescription refill.

“Patients in this study appeared to be using the urgent care centers specifically for acute care,” the researchers said. “The patients generally had infrequent headaches and the majority would not have qualified for migraine preventive treatment.”

Although AHS guidelines include three “should offer” medications for acute management of migraine in the ED – intravenous metoclopramide, intravenous prochlorperazine, and subcutaneous sumatriptan – two of the medications, subcutaneous sumatriptan and intravenous prochlorperazine, were not available in the urgent care pharmacy. “Of the level B migraine medications, only metoclopramide IV was in the pharmacy, and only 12.3% was given this at their urgent care visit,” the researchers said. “There was also likely undertreatment of nausea/vomiting; despite 39 patients with recorded nausea or vomiting with their migraine, less than half (46.2%) received an antiemetic at the visit,” including metoclopramide or ondansetron through oral or intravenous administration.

Future studies should look at headache and migraine visits at urgent care centers across the United States, the investigators suggested.

One of the authors of the study (Leslie Miller, MD) is the head of the NYU Langone Health Urgent Care Centers. Dr. Minen has received grant support, honoraria, or travel funds from the National Institutes of Health, the American Academy of Neurology, the American Brain Foundation, the National Multiple Sclerosis Society, the National Headache Foundation, the American Headache Society, Barnard College, and NYU. Dr. Minen is associate editor of Headache.

[email protected]

SOURCE: Minen MT et al. Headache. 2020;60(3):542-52.

Urgent care centers may not use optimal medications for the management of acute migraine attacks, according to a study published in the March issue of Headache. Pain and nausea or vomiting associated with migraine may go undertreated, and treatment may not be consistent with American Headache Society (AHS) guidelines for EDs, said Mia T. Minen, MD, of the department of neurology and population health at NYU Langone Health in New York and colleagues.

“Our study findings raise the question as to whether the patients with migraine in the urgent care setting should be managed similarly to the ED, and whether the AHS guidelines for the ED should be revisited and applied to urgent care,” the researchers noted.

Relative to the ED, urgent care centers may provide cost savings and emerge “as a preferred place for treatment for people with migraine, perhaps as they are potentially more quiet medical settings where people with migraine might expeditiously receive care,” the authors said.

Dr. Minen and colleagues conducted a retrospective chart review to assess migraine management at two urgent care centers in New York. They examined the number of urgent care visits for migraine, treatments used, and how closely clinicians followed the AHS recommendations for administration of antiemetic medication and triptans, among other outcomes.

The study population included adults diagnosed with migraine at the NYU Langone Medhattan Urgent Care center between Dec. 1, 2015, and Dec. 1, 2018, or at the NYU Langone Ambulatory Care Urgent Care West Side center between May 1, 2017, and Dec. 1, 2018. Of more than 32,000 urgent care visits during the study period, 78 patients received a migraine diagnosis. Patients with migraine had an average age of 32.5 years, and 79.5% were female. More than half had a documented history of migraine. Two of the patients (2.6%) had been to an emergency department for headache or migraine.

Less than half of the patients who presented with pain (46.6%) were given medication, most commonly ketorolac injection. Most patients (78.2%) received prescriptions, and 25.6% received a triptan prescription. About 60% of patients were told to follow up with a neurologist. In addition, 11.5% revisited urgent care with a migraine or headache or to request a prescription refill.

“Patients in this study appeared to be using the urgent care centers specifically for acute care,” the researchers said. “The patients generally had infrequent headaches and the majority would not have qualified for migraine preventive treatment.”

Although AHS guidelines include three “should offer” medications for acute management of migraine in the ED – intravenous metoclopramide, intravenous prochlorperazine, and subcutaneous sumatriptan – two of the medications, subcutaneous sumatriptan and intravenous prochlorperazine, were not available in the urgent care pharmacy. “Of the level B migraine medications, only metoclopramide IV was in the pharmacy, and only 12.3% was given this at their urgent care visit,” the researchers said. “There was also likely undertreatment of nausea/vomiting; despite 39 patients with recorded nausea or vomiting with their migraine, less than half (46.2%) received an antiemetic at the visit,” including metoclopramide or ondansetron through oral or intravenous administration.

Future studies should look at headache and migraine visits at urgent care centers across the United States, the investigators suggested.

One of the authors of the study (Leslie Miller, MD) is the head of the NYU Langone Health Urgent Care Centers. Dr. Minen has received grant support, honoraria, or travel funds from the National Institutes of Health, the American Academy of Neurology, the American Brain Foundation, the National Multiple Sclerosis Society, the National Headache Foundation, the American Headache Society, Barnard College, and NYU. Dr. Minen is associate editor of Headache.

[email protected]

SOURCE: Minen MT et al. Headache. 2020;60(3):542-52.

Urgent care centers may not use optimal medications for the management of acute migraine attacks, according to a study published in the March issue of Headache. Pain and nausea or vomiting associated with migraine may go undertreated, and treatment may not be consistent with American Headache Society (AHS) guidelines for EDs, said Mia T. Minen, MD, of the department of neurology and population health at NYU Langone Health in New York and colleagues.

“Our study findings raise the question as to whether the patients with migraine in the urgent care setting should be managed similarly to the ED, and whether the AHS guidelines for the ED should be revisited and applied to urgent care,” the researchers noted.

Relative to the ED, urgent care centers may provide cost savings and emerge “as a preferred place for treatment for people with migraine, perhaps as they are potentially more quiet medical settings where people with migraine might expeditiously receive care,” the authors said.

Dr. Minen and colleagues conducted a retrospective chart review to assess migraine management at two urgent care centers in New York. They examined the number of urgent care visits for migraine, treatments used, and how closely clinicians followed the AHS recommendations for administration of antiemetic medication and triptans, among other outcomes.

The study population included adults diagnosed with migraine at the NYU Langone Medhattan Urgent Care center between Dec. 1, 2015, and Dec. 1, 2018, or at the NYU Langone Ambulatory Care Urgent Care West Side center between May 1, 2017, and Dec. 1, 2018. Of more than 32,000 urgent care visits during the study period, 78 patients received a migraine diagnosis. Patients with migraine had an average age of 32.5 years, and 79.5% were female. More than half had a documented history of migraine. Two of the patients (2.6%) had been to an emergency department for headache or migraine.

Less than half of the patients who presented with pain (46.6%) were given medication, most commonly ketorolac injection. Most patients (78.2%) received prescriptions, and 25.6% received a triptan prescription. About 60% of patients were told to follow up with a neurologist. In addition, 11.5% revisited urgent care with a migraine or headache or to request a prescription refill.

“Patients in this study appeared to be using the urgent care centers specifically for acute care,” the researchers said. “The patients generally had infrequent headaches and the majority would not have qualified for migraine preventive treatment.”

Although AHS guidelines include three “should offer” medications for acute management of migraine in the ED – intravenous metoclopramide, intravenous prochlorperazine, and subcutaneous sumatriptan – two of the medications, subcutaneous sumatriptan and intravenous prochlorperazine, were not available in the urgent care pharmacy. “Of the level B migraine medications, only metoclopramide IV was in the pharmacy, and only 12.3% was given this at their urgent care visit,” the researchers said. “There was also likely undertreatment of nausea/vomiting; despite 39 patients with recorded nausea or vomiting with their migraine, less than half (46.2%) received an antiemetic at the visit,” including metoclopramide or ondansetron through oral or intravenous administration.

Future studies should look at headache and migraine visits at urgent care centers across the United States, the investigators suggested.

One of the authors of the study (Leslie Miller, MD) is the head of the NYU Langone Health Urgent Care Centers. Dr. Minen has received grant support, honoraria, or travel funds from the National Institutes of Health, the American Academy of Neurology, the American Brain Foundation, the National Multiple Sclerosis Society, the National Headache Foundation, the American Headache Society, Barnard College, and NYU. Dr. Minen is associate editor of Headache.

[email protected]

SOURCE: Minen MT et al. Headache. 2020;60(3):542-52.

LOS ANGELES – Investigators have developed a risk score to predict the likelihood of stroke among patients with migraine with aura. The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.

Risk groups significantly discriminated stroke risk

To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.

Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).

After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.

Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.

Score may leave important variables unexamined

One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.

Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.

Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.

[email protected]

SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.

LOS ANGELES – Investigators have developed a risk score to predict the likelihood of stroke among patients with migraine with aura. The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.

Risk groups significantly discriminated stroke risk

To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.

Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).

After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.

Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.

Score may leave important variables unexamined

One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.

Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.

Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.

[email protected]

SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.

LOS ANGELES – Investigators have developed a risk score to predict the likelihood of stroke among patients with migraine with aura. The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.

Risk groups significantly discriminated stroke risk

To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.

Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).

After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.

Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.

Score may leave important variables unexamined

One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.

Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.

Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.

[email protected]

SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.

Martha Clare Morris, ScD, a pioneer in research linking nutrition to brain health and a creator of the breakthrough MIND diet, has died of cancer at the age of 64.

Morris was a professor in the Department of Internal Medicine, assistant provost of community research, and director of the Rush Institute for Healthy Aging at Rush University, in Chicago, Illinois. She was also a director of the internal medicine department’s Section of Community Epidemiology.

Long-time friend and colleague Julie A. Schneider, MD, the Deborah R. and Edgar D. Jannotta Presidential Professor of Pathology and Neurological Sciences, Rush University Medical Center, described Morris as creative, passionate, and adventurous.

Her death was “a shock” to the scientific community, Schneider told Medscape Medical News.

“It’s a tragic loss in so many ways,” said Schneider, who is also associate director of the Rush Alzheimer’s Disease Center. She was a very well-respected nutritional epidemiologist and was passionate about her work; she had just so much unwavering commitment to it.

Diet, said Schneider, is “notoriously a hard thing to study” because “it’s so intertwined with lifestyle” and other factors that create “barriers” to conducting such research.

But Morris had a unique and creative talent for filtering out what might be the individual contribution of a particular modifiable risk factor, said Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, who also knew Morris both personally and professionally.

“Humble” trailblazer

Morris’s pioneering research examined the connection between nutrition and the prevention of cognitive decline. Taking results from this research, she developed the MIND diet – a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension – along with colleagues at both Rush and Harvard Universities.

The MIND diet – an acronym for Mediterranean-DASH Intervention for Neurodegenerative Delay – emphasizes brain-healthy foods, including leafy green vegetables, nuts, berries, chicken, fish, whole grains, beans, olive oil, and moderate amounts of red wine. The diet limits consumption of red meat, butter, margarine, and processed foods.

In 2015, Morris published her initial findings on the MIND diet in Alzheimer’s and Dementia. Reported by Medscape Medical News at that time, the study showed that the diet protected cardiovascular health and slowed cognitive decline in older individuals.

The excitement around the findings inspired Morris to write “Diet for the Mind,” which was published in 2017. The book summarizes the benefits of the MIND diet and includes brain-healthy recipes created by her daughter Laura, who is a chef. Despite many accolades, Morris was “humble” about this project, said Schneider.

“This was not about publicity and trying to get a book out; she wanted to see if this diet really was going to change people’s lives. She wanted to bring it into the community,” she said.

Proud legacy

Since 2017, Morris had led a large clinical trial of the effectiveness of the MIND diet in preventing cognitive decline. The first study of its kind, the trial received a $14.5 million grant from the National Institutes of Health (NIH). Results of this study are expected in 2021.

The MIND diet was ranked among the top 10 diets for five consecutive years in US News and World Report.

Morris’s nutrition-related research went beyond diets and examined the impact of individual nutrients. One of her studies, published in 2018 and reported by Medscape Medical News, suggested that the presence of folate, phylloquinone, and lutein – nutrients found in relatively large amounts in green leafy vegetables – may account for why consuming a daily serving of these vegetables slows cognitive decline.

One of the most recent studies from Morris’ group, published in January 2020 and reported by Medscape Medical News at that time, provided the first evidence that dietary flavonols, which are found in many fruits and vegetables, are associated with a significantly reduced risk for dementia.

What Morris did so well was to “look at the big picture” and “think about commonalities that cross nutritional components” of diets such as MIND, DASH, the Mediterranean diet, and the Nordic diet, which is similar to the Mediterranean diet but highlights local foods such as fish from Nordic regions, Snyder told Medscape Medical News.

Morris was instrumental in getting the Alzheimer’s Association’s US POINTER (US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk) study off the ground. The 2-year clinical trial is testing whether combining a healthy diet with exercise, cognitive and social stimulation, and the management of cardiovascular conditions protects cognitive function in older adults who are at increased risk for cognitive decline.

This study will be part of her legacy, said Snyder.

“She will be remembered for her perseverance to get us to a place where we can be looking at nutrition as a modifiable risk factor and now testing it in trials that she helped to set up,” she said.

Even before her involvement with US POINTER, Morris had long been an active volunteer for the Alzheimer’s Association, said Snyder.

“She contributed significant time and expertise as we looked at the state of the evidence around nutrition and other lifestyle and behavioral interventions.”

We’ll ‘always have Paris’

While Morris was “truly passionate” about diet and health “both professionally and personally,” she also had a fun side, said Schneider. She remembers she and Morris had a chance meeting in Paris, where they spent an entire day going to museums and restaurants and just talking about life and their travels. To the end, they joked they would “always have Paris,” said Schneider.

She was also a loyal friend. Morris threw a baby shower when Schneider was pregnant, organizing every detail, despite her extremely busy schedule.

Family was another of Morris’s passions. Snyder recalls Morris’s face lighting up when she talked about her children and grandchildren. She also remembers her friend’s zest for life. “She had an energy that was contagious.”

Morris also loved the outdoors and was a keen adventurer. She once trained for weeks before a long bike trip with her daughter and would take a helicopter to access remote backcountry on hiking excursions.

“She wanted to try everything,” said Schneider.

An author or contributor to more than 80 articles in peer-reviewed journals, Morris also served two terms (from 2011 to 2013) as chair of the NIH’s Neurological, Aging and Musculoskeletal Epidemiology Study Section.

She left behind multiple grants for various studies. One unique study, said Schneider, investigated the relationship between iron and other metals in the brain and the neuropathology of Alzheimer disease.

“She was really in the prime of her career,” noted Schneider. “She had so much left to give and to offer, so this is tremendously sad.”

According to news reports, Morris (nee Chinn) grew up in Homewood, Illinois, and earned bachelor’s and master’s degrees in sociology from the University of Iowa in Iowa City, where she met her husband, James Morris. The two married in 1978 and had three children.

Morris completed a doctorate in epidemiology at the Harvard School of Public Health. James died in 2012, also from cancer. Morris passed away peacefully at her home on February 15.

Martha Clare Morris, ScD, a pioneer in research linking nutrition to brain health and a creator of the breakthrough MIND diet, has died of cancer at the age of 64.

Morris was a professor in the Department of Internal Medicine, assistant provost of community research, and director of the Rush Institute for Healthy Aging at Rush University, in Chicago, Illinois. She was also a director of the internal medicine department’s Section of Community Epidemiology.

Long-time friend and colleague Julie A. Schneider, MD, the Deborah R. and Edgar D. Jannotta Presidential Professor of Pathology and Neurological Sciences, Rush University Medical Center, described Morris as creative, passionate, and adventurous.

Her death was “a shock” to the scientific community, Schneider told Medscape Medical News.

“It’s a tragic loss in so many ways,” said Schneider, who is also associate director of the Rush Alzheimer’s Disease Center. She was a very well-respected nutritional epidemiologist and was passionate about her work; she had just so much unwavering commitment to it.

Diet, said Schneider, is “notoriously a hard thing to study” because “it’s so intertwined with lifestyle” and other factors that create “barriers” to conducting such research.

But Morris had a unique and creative talent for filtering out what might be the individual contribution of a particular modifiable risk factor, said Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, who also knew Morris both personally and professionally.

“Humble” trailblazer

Morris’s pioneering research examined the connection between nutrition and the prevention of cognitive decline. Taking results from this research, she developed the MIND diet – a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension – along with colleagues at both Rush and Harvard Universities.

The MIND diet – an acronym for Mediterranean-DASH Intervention for Neurodegenerative Delay – emphasizes brain-healthy foods, including leafy green vegetables, nuts, berries, chicken, fish, whole grains, beans, olive oil, and moderate amounts of red wine. The diet limits consumption of red meat, butter, margarine, and processed foods.

In 2015, Morris published her initial findings on the MIND diet in Alzheimer’s and Dementia. Reported by Medscape Medical News at that time, the study showed that the diet protected cardiovascular health and slowed cognitive decline in older individuals.

The excitement around the findings inspired Morris to write “Diet for the Mind,” which was published in 2017. The book summarizes the benefits of the MIND diet and includes brain-healthy recipes created by her daughter Laura, who is a chef. Despite many accolades, Morris was “humble” about this project, said Schneider.

“This was not about publicity and trying to get a book out; she wanted to see if this diet really was going to change people’s lives. She wanted to bring it into the community,” she said.

Proud legacy

Since 2017, Morris had led a large clinical trial of the effectiveness of the MIND diet in preventing cognitive decline. The first study of its kind, the trial received a $14.5 million grant from the National Institutes of Health (NIH). Results of this study are expected in 2021.

The MIND diet was ranked among the top 10 diets for five consecutive years in US News and World Report.

Morris’s nutrition-related research went beyond diets and examined the impact of individual nutrients. One of her studies, published in 2018 and reported by Medscape Medical News, suggested that the presence of folate, phylloquinone, and lutein – nutrients found in relatively large amounts in green leafy vegetables – may account for why consuming a daily serving of these vegetables slows cognitive decline.

One of the most recent studies from Morris’ group, published in January 2020 and reported by Medscape Medical News at that time, provided the first evidence that dietary flavonols, which are found in many fruits and vegetables, are associated with a significantly reduced risk for dementia.

What Morris did so well was to “look at the big picture” and “think about commonalities that cross nutritional components” of diets such as MIND, DASH, the Mediterranean diet, and the Nordic diet, which is similar to the Mediterranean diet but highlights local foods such as fish from Nordic regions, Snyder told Medscape Medical News.

Morris was instrumental in getting the Alzheimer’s Association’s US POINTER (US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk) study off the ground. The 2-year clinical trial is testing whether combining a healthy diet with exercise, cognitive and social stimulation, and the management of cardiovascular conditions protects cognitive function in older adults who are at increased risk for cognitive decline.

This study will be part of her legacy, said Snyder.

“She will be remembered for her perseverance to get us to a place where we can be looking at nutrition as a modifiable risk factor and now testing it in trials that she helped to set up,” she said.

Even before her involvement with US POINTER, Morris had long been an active volunteer for the Alzheimer’s Association, said Snyder.

“She contributed significant time and expertise as we looked at the state of the evidence around nutrition and other lifestyle and behavioral interventions.”

We’ll ‘always have Paris’

While Morris was “truly passionate” about diet and health “both professionally and personally,” she also had a fun side, said Schneider. She remembers she and Morris had a chance meeting in Paris, where they spent an entire day going to museums and restaurants and just talking about life and their travels. To the end, they joked they would “always have Paris,” said Schneider.

She was also a loyal friend. Morris threw a baby shower when Schneider was pregnant, organizing every detail, despite her extremely busy schedule.

Family was another of Morris’s passions. Snyder recalls Morris’s face lighting up when she talked about her children and grandchildren. She also remembers her friend’s zest for life. “She had an energy that was contagious.”

Morris also loved the outdoors and was a keen adventurer. She once trained for weeks before a long bike trip with her daughter and would take a helicopter to access remote backcountry on hiking excursions.

“She wanted to try everything,” said Schneider.

An author or contributor to more than 80 articles in peer-reviewed journals, Morris also served two terms (from 2011 to 2013) as chair of the NIH’s Neurological, Aging and Musculoskeletal Epidemiology Study Section.

She left behind multiple grants for various studies. One unique study, said Schneider, investigated the relationship between iron and other metals in the brain and the neuropathology of Alzheimer disease.

“She was really in the prime of her career,” noted Schneider. “She had so much left to give and to offer, so this is tremendously sad.”

According to news reports, Morris (nee Chinn) grew up in Homewood, Illinois, and earned bachelor’s and master’s degrees in sociology from the University of Iowa in Iowa City, where she met her husband, James Morris. The two married in 1978 and had three children.

Morris completed a doctorate in epidemiology at the Harvard School of Public Health. James died in 2012, also from cancer. Morris passed away peacefully at her home on February 15.

Martha Clare Morris, ScD, a pioneer in research linking nutrition to brain health and a creator of the breakthrough MIND diet, has died of cancer at the age of 64.

Morris was a professor in the Department of Internal Medicine, assistant provost of community research, and director of the Rush Institute for Healthy Aging at Rush University, in Chicago, Illinois. She was also a director of the internal medicine department’s Section of Community Epidemiology.

Long-time friend and colleague Julie A. Schneider, MD, the Deborah R. and Edgar D. Jannotta Presidential Professor of Pathology and Neurological Sciences, Rush University Medical Center, described Morris as creative, passionate, and adventurous.

Her death was “a shock” to the scientific community, Schneider told Medscape Medical News.

“It’s a tragic loss in so many ways,” said Schneider, who is also associate director of the Rush Alzheimer’s Disease Center. She was a very well-respected nutritional epidemiologist and was passionate about her work; she had just so much unwavering commitment to it.

Diet, said Schneider, is “notoriously a hard thing to study” because “it’s so intertwined with lifestyle” and other factors that create “barriers” to conducting such research.

But Morris had a unique and creative talent for filtering out what might be the individual contribution of a particular modifiable risk factor, said Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, who also knew Morris both personally and professionally.

“Humble” trailblazer

Morris’s pioneering research examined the connection between nutrition and the prevention of cognitive decline. Taking results from this research, she developed the MIND diet – a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension – along with colleagues at both Rush and Harvard Universities.

The MIND diet – an acronym for Mediterranean-DASH Intervention for Neurodegenerative Delay – emphasizes brain-healthy foods, including leafy green vegetables, nuts, berries, chicken, fish, whole grains, beans, olive oil, and moderate amounts of red wine. The diet limits consumption of red meat, butter, margarine, and processed foods.

In 2015, Morris published her initial findings on the MIND diet in Alzheimer’s and Dementia. Reported by Medscape Medical News at that time, the study showed that the diet protected cardiovascular health and slowed cognitive decline in older individuals.

The excitement around the findings inspired Morris to write “Diet for the Mind,” which was published in 2017. The book summarizes the benefits of the MIND diet and includes brain-healthy recipes created by her daughter Laura, who is a chef. Despite many accolades, Morris was “humble” about this project, said Schneider.

“This was not about publicity and trying to get a book out; she wanted to see if this diet really was going to change people’s lives. She wanted to bring it into the community,” she said.

Proud legacy

Since 2017, Morris had led a large clinical trial of the effectiveness of the MIND diet in preventing cognitive decline. The first study of its kind, the trial received a $14.5 million grant from the National Institutes of Health (NIH). Results of this study are expected in 2021.

The MIND diet was ranked among the top 10 diets for five consecutive years in US News and World Report.

Morris’s nutrition-related research went beyond diets and examined the impact of individual nutrients. One of her studies, published in 2018 and reported by Medscape Medical News, suggested that the presence of folate, phylloquinone, and lutein – nutrients found in relatively large amounts in green leafy vegetables – may account for why consuming a daily serving of these vegetables slows cognitive decline.

One of the most recent studies from Morris’ group, published in January 2020 and reported by Medscape Medical News at that time, provided the first evidence that dietary flavonols, which are found in many fruits and vegetables, are associated with a significantly reduced risk for dementia.

What Morris did so well was to “look at the big picture” and “think about commonalities that cross nutritional components” of diets such as MIND, DASH, the Mediterranean diet, and the Nordic diet, which is similar to the Mediterranean diet but highlights local foods such as fish from Nordic regions, Snyder told Medscape Medical News.

Morris was instrumental in getting the Alzheimer’s Association’s US POINTER (US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk) study off the ground. The 2-year clinical trial is testing whether combining a healthy diet with exercise, cognitive and social stimulation, and the management of cardiovascular conditions protects cognitive function in older adults who are at increased risk for cognitive decline.

This study will be part of her legacy, said Snyder.

“She will be remembered for her perseverance to get us to a place where we can be looking at nutrition as a modifiable risk factor and now testing it in trials that she helped to set up,” she said.

Even before her involvement with US POINTER, Morris had long been an active volunteer for the Alzheimer’s Association, said Snyder.

“She contributed significant time and expertise as we looked at the state of the evidence around nutrition and other lifestyle and behavioral interventions.”

We’ll ‘always have Paris’

While Morris was “truly passionate” about diet and health “both professionally and personally,” she also had a fun side, said Schneider. She remembers she and Morris had a chance meeting in Paris, where they spent an entire day going to museums and restaurants and just talking about life and their travels. To the end, they joked they would “always have Paris,” said Schneider.

She was also a loyal friend. Morris threw a baby shower when Schneider was pregnant, organizing every detail, despite her extremely busy schedule.

Family was another of Morris’s passions. Snyder recalls Morris’s face lighting up when she talked about her children and grandchildren. She also remembers her friend’s zest for life. “She had an energy that was contagious.”

Morris also loved the outdoors and was a keen adventurer. She once trained for weeks before a long bike trip with her daughter and would take a helicopter to access remote backcountry on hiking excursions.

“She wanted to try everything,” said Schneider.

An author or contributor to more than 80 articles in peer-reviewed journals, Morris also served two terms (from 2011 to 2013) as chair of the NIH’s Neurological, Aging and Musculoskeletal Epidemiology Study Section.

She left behind multiple grants for various studies. One unique study, said Schneider, investigated the relationship between iron and other metals in the brain and the neuropathology of Alzheimer disease.

“She was really in the prime of her career,” noted Schneider. “She had so much left to give and to offer, so this is tremendously sad.”

According to news reports, Morris (nee Chinn) grew up in Homewood, Illinois, and earned bachelor’s and master’s degrees in sociology from the University of Iowa in Iowa City, where she met her husband, James Morris. The two married in 1978 and had three children.

Morris completed a doctorate in epidemiology at the Harvard School of Public Health. James died in 2012, also from cancer. Morris passed away peacefully at her home on February 15.

WEST PALM BEACH, FLA. – As disease duration increases, patients with pediatric-onset multiple sclerosis (POMS) have an increased rate of impairment in manual dexterity, compared with patients with adult-onset MS (AOMS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

When MS onset occurs before the patient is age 18 years, the patient is considered to have POMS. Compared with AOMS, POMS is less prevalent and has distinct features. To determine whether changes in physical performance differ between POMS and AOMS, Sarah M. Planchon, PhD, a project scientist at the Mellen Center for MS at the Cleveland Clinic, and colleagues analyzed data cut 9 from the MS PATHS (MS Partners Advancing Technology and Health Solutions) initiative. As part of this initiative, which is sponsored by Biogen, investigators collect MS performance measures longitudinally at each patient visit. Among these measures are the manual dexterity test (MDT), an iPad version of the Nine-Hole Peg Test, and the walking speed test (WST), which is the iPad version of the Timed 25-Foot Walk.

Dr. Planchon and colleagues matched each patient with POMS to five patients with AOMS according to disease duration. They calculated descriptive statistics for the sample and performed Tukey’s honestly significant difference test to compare patient groups on several categorical variables.
 

Overall, function was better in POMS than in AOMS

The investigators included 3 years’ worth of data from 6,457 patients in their analysis. The average age was approximately 50 years for patients with AOMS and 31 years for patients with POMS. The time elapsed since diagnosis was approximately 14 years in the AOMS group and 17 years in the POMS group. The proportion of female patients was about 74% in the AOMS group and 73% in the POMS group. Compared with the AOMS group, the POMS group had higher proportions of patients who were Asian (0.5% vs 2.6%), black (9.3% vs 11.5%), and other race (2.8% vs 9.3%).

Overall, patients with POMS performed better than patients with AOMS by 1.39 seconds on the MDT and by 0.79 seconds on the WST. Regression analyses indicated that with increasing age, patients with AOMS declined more quickly on the MDT and the WST than patients with POMS did. When the investigators stratified the results by disease duration, however, patients with POMS declined more rapidly on the MDT than did patients with AOMS. There was no significant difference between groups in WST in this analysis. When Dr. Planchon and colleagues performed linear regression and adjusted for variables such as age, sex, race, education, insurance, employment, MS phenotype, disease duration, number of relapses, and Patient-Determined Disease Steps (PDDS), the MS onset type did not significantly affect outcomes. Age, sex, PDDS, and MS type were significant covariates for both tests.
 

The role of occupational and physical therapy

“POMS patients tend to have a greater dysfunction of the cerebellar and brainstem regions of the brain, both of which may impact motor skills to a greater degree than other regions of the brain,” said Dr. Planchon. The increased rate of manual impairment in POMS, compared with AOMS, does not necessarily indicate more severe disease, she added. Getting a true picture of disease severity would require consideration of factors such as ambulation, cognitive functioning, vision, fatigue, and depression.

“We would recommend introducing POMS patients to occupational and physical therapy early in their disease course, before significant deficits accrue,” said Dr. Planchon. “Early familiarity with rehabilitation services should help the patient and family optimize what exercises are being done to improve and maintain function.”

The optimal pharmacologic treatment for POMS is unknown. One therapy (i.e., fingolimod) has Food and Drug Administration approval, and clinical trials of other treatments are ongoing. Some MS treatments not indicated for a pediatric population are used off label in children.

“We plan to delve deeper into the data set, including using regression modeling to try to better define differences between individuals with POMS and AOMS that may lead to the functional outcome changes we have already observed,” said Dr. Planchon. “We also plan to investigate further the impact of POMS on cognition and quality of life measures and to better understand disease-modifying therapy prescribing patterns and benefits in individuals with POMS. We will look for associations in the MRI imaging findings and various biomarkers to help us understand the disease process in this special population of MS.”

Dr. Planchon has received research support from the Guthy-Jackson Charitable Foundation. Her coinvestigators received funding from Biogen, Genentech, Genzyme, MedImmune, Novartis, Serono, and Teva.

[email protected]

SOURCE: Planchon SM et al. ACTRIMS 2020. Abstract P043.

WEST PALM BEACH, FLA. – As disease duration increases, patients with pediatric-onset multiple sclerosis (POMS) have an increased rate of impairment in manual dexterity, compared with patients with adult-onset MS (AOMS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

When MS onset occurs before the patient is age 18 years, the patient is considered to have POMS. Compared with AOMS, POMS is less prevalent and has distinct features. To determine whether changes in physical performance differ between POMS and AOMS, Sarah M. Planchon, PhD, a project scientist at the Mellen Center for MS at the Cleveland Clinic, and colleagues analyzed data cut 9 from the MS PATHS (MS Partners Advancing Technology and Health Solutions) initiative. As part of this initiative, which is sponsored by Biogen, investigators collect MS performance measures longitudinally at each patient visit. Among these measures are the manual dexterity test (MDT), an iPad version of the Nine-Hole Peg Test, and the walking speed test (WST), which is the iPad version of the Timed 25-Foot Walk.

Dr. Planchon and colleagues matched each patient with POMS to five patients with AOMS according to disease duration. They calculated descriptive statistics for the sample and performed Tukey’s honestly significant difference test to compare patient groups on several categorical variables.
 

Overall, function was better in POMS than in AOMS

The investigators included 3 years’ worth of data from 6,457 patients in their analysis. The average age was approximately 50 years for patients with AOMS and 31 years for patients with POMS. The time elapsed since diagnosis was approximately 14 years in the AOMS group and 17 years in the POMS group. The proportion of female patients was about 74% in the AOMS group and 73% in the POMS group. Compared with the AOMS group, the POMS group had higher proportions of patients who were Asian (0.5% vs 2.6%), black (9.3% vs 11.5%), and other race (2.8% vs 9.3%).

Overall, patients with POMS performed better than patients with AOMS by 1.39 seconds on the MDT and by 0.79 seconds on the WST. Regression analyses indicated that with increasing age, patients with AOMS declined more quickly on the MDT and the WST than patients with POMS did. When the investigators stratified the results by disease duration, however, patients with POMS declined more rapidly on the MDT than did patients with AOMS. There was no significant difference between groups in WST in this analysis. When Dr. Planchon and colleagues performed linear regression and adjusted for variables such as age, sex, race, education, insurance, employment, MS phenotype, disease duration, number of relapses, and Patient-Determined Disease Steps (PDDS), the MS onset type did not significantly affect outcomes. Age, sex, PDDS, and MS type were significant covariates for both tests.
 

The role of occupational and physical therapy

“POMS patients tend to have a greater dysfunction of the cerebellar and brainstem regions of the brain, both of which may impact motor skills to a greater degree than other regions of the brain,” said Dr. Planchon. The increased rate of manual impairment in POMS, compared with AOMS, does not necessarily indicate more severe disease, she added. Getting a true picture of disease severity would require consideration of factors such as ambulation, cognitive functioning, vision, fatigue, and depression.

“We would recommend introducing POMS patients to occupational and physical therapy early in their disease course, before significant deficits accrue,” said Dr. Planchon. “Early familiarity with rehabilitation services should help the patient and family optimize what exercises are being done to improve and maintain function.”

The optimal pharmacologic treatment for POMS is unknown. One therapy (i.e., fingolimod) has Food and Drug Administration approval, and clinical trials of other treatments are ongoing. Some MS treatments not indicated for a pediatric population are used off label in children.

“We plan to delve deeper into the data set, including using regression modeling to try to better define differences between individuals with POMS and AOMS that may lead to the functional outcome changes we have already observed,” said Dr. Planchon. “We also plan to investigate further the impact of POMS on cognition and quality of life measures and to better understand disease-modifying therapy prescribing patterns and benefits in individuals with POMS. We will look for associations in the MRI imaging findings and various biomarkers to help us understand the disease process in this special population of MS.”

Dr. Planchon has received research support from the Guthy-Jackson Charitable Foundation. Her coinvestigators received funding from Biogen, Genentech, Genzyme, MedImmune, Novartis, Serono, and Teva.

[email protected]

SOURCE: Planchon SM et al. ACTRIMS 2020. Abstract P043.

WEST PALM BEACH, FLA. – As disease duration increases, patients with pediatric-onset multiple sclerosis (POMS) have an increased rate of impairment in manual dexterity, compared with patients with adult-onset MS (AOMS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

When MS onset occurs before the patient is age 18 years, the patient is considered to have POMS. Compared with AOMS, POMS is less prevalent and has distinct features. To determine whether changes in physical performance differ between POMS and AOMS, Sarah M. Planchon, PhD, a project scientist at the Mellen Center for MS at the Cleveland Clinic, and colleagues analyzed data cut 9 from the MS PATHS (MS Partners Advancing Technology and Health Solutions) initiative. As part of this initiative, which is sponsored by Biogen, investigators collect MS performance measures longitudinally at each patient visit. Among these measures are the manual dexterity test (MDT), an iPad version of the Nine-Hole Peg Test, and the walking speed test (WST), which is the iPad version of the Timed 25-Foot Walk.

Dr. Planchon and colleagues matched each patient with POMS to five patients with AOMS according to disease duration. They calculated descriptive statistics for the sample and performed Tukey’s honestly significant difference test to compare patient groups on several categorical variables.
 

Overall, function was better in POMS than in AOMS

The investigators included 3 years’ worth of data from 6,457 patients in their analysis. The average age was approximately 50 years for patients with AOMS and 31 years for patients with POMS. The time elapsed since diagnosis was approximately 14 years in the AOMS group and 17 years in the POMS group. The proportion of female patients was about 74% in the AOMS group and 73% in the POMS group. Compared with the AOMS group, the POMS group had higher proportions of patients who were Asian (0.5% vs 2.6%), black (9.3% vs 11.5%), and other race (2.8% vs 9.3%).

Overall, patients with POMS performed better than patients with AOMS by 1.39 seconds on the MDT and by 0.79 seconds on the WST. Regression analyses indicated that with increasing age, patients with AOMS declined more quickly on the MDT and the WST than patients with POMS did. When the investigators stratified the results by disease duration, however, patients with POMS declined more rapidly on the MDT than did patients with AOMS. There was no significant difference between groups in WST in this analysis. When Dr. Planchon and colleagues performed linear regression and adjusted for variables such as age, sex, race, education, insurance, employment, MS phenotype, disease duration, number of relapses, and Patient-Determined Disease Steps (PDDS), the MS onset type did not significantly affect outcomes. Age, sex, PDDS, and MS type were significant covariates for both tests.
 

The role of occupational and physical therapy

“POMS patients tend to have a greater dysfunction of the cerebellar and brainstem regions of the brain, both of which may impact motor skills to a greater degree than other regions of the brain,” said Dr. Planchon. The increased rate of manual impairment in POMS, compared with AOMS, does not necessarily indicate more severe disease, she added. Getting a true picture of disease severity would require consideration of factors such as ambulation, cognitive functioning, vision, fatigue, and depression.

“We would recommend introducing POMS patients to occupational and physical therapy early in their disease course, before significant deficits accrue,” said Dr. Planchon. “Early familiarity with rehabilitation services should help the patient and family optimize what exercises are being done to improve and maintain function.”

The optimal pharmacologic treatment for POMS is unknown. One therapy (i.e., fingolimod) has Food and Drug Administration approval, and clinical trials of other treatments are ongoing. Some MS treatments not indicated for a pediatric population are used off label in children.

“We plan to delve deeper into the data set, including using regression modeling to try to better define differences between individuals with POMS and AOMS that may lead to the functional outcome changes we have already observed,” said Dr. Planchon. “We also plan to investigate further the impact of POMS on cognition and quality of life measures and to better understand disease-modifying therapy prescribing patterns and benefits in individuals with POMS. We will look for associations in the MRI imaging findings and various biomarkers to help us understand the disease process in this special population of MS.”

Dr. Planchon has received research support from the Guthy-Jackson Charitable Foundation. Her coinvestigators received funding from Biogen, Genentech, Genzyme, MedImmune, Novartis, Serono, and Teva.

[email protected]

SOURCE: Planchon SM et al. ACTRIMS 2020. Abstract P043.

WEST PALM BEACH, FLA. – The use of a disease-modifying therapy (DMT) is common among older patients with multiple sclerosis even though DMTs may be less effective in this population, according to a review of clinical trial results and registry data.

MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.

“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.

The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”

In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.

Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.

A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.

Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.

[email protected]

SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.

WEST PALM BEACH, FLA. – The use of a disease-modifying therapy (DMT) is common among older patients with multiple sclerosis even though DMTs may be less effective in this population, according to a review of clinical trial results and registry data.

MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.

“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.

The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”

In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.

Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.

A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.

Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.

[email protected]

SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.

WEST PALM BEACH, FLA. – The use of a disease-modifying therapy (DMT) is common among older patients with multiple sclerosis even though DMTs may be less effective in this population, according to a review of clinical trial results and registry data.

MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.

“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.

The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”

In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.

Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.

A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.

Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.

[email protected]

SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.

Patients with suspected migraine and a normal neurological examination without any atypical features or red flags do not need an MRI or CT, according to recent updated recommendations in a guideline released by the American Headache Society.

Migraine with atypical features may require neuroimaging, according to the guideline. These include an unusual aura; change in clinical features; a first or worst migraine; a migraine that presents with brainstem aura, confusion, or motor manifestation; migraine accompaniments in later life; headaches that are side-locked or posttraumatic; and aura that presents without headache.
 

Assessing the evidence

The recommendation to avoid MRI or CT in otherwise neurologically normal patients with migraine carried a grade A recommendation from the American Headache Society, while the specific considerations for neuroimaging was based on consensus and carried a grade C recommendation, according to lead author Randolph W. Evans, MD, of the department of neurology at Baylor College of Medicine in Houston, and colleagues.

The recommendations, published in the journal Headache (2020 Feb;60(2):318-36), came from a systematic review of 23 studies of adults at least 18 years old who underwent MRI or CT during outpatient treatment for migraine between 1973 and 2018. Ten studies looked at CT neuroimaging in patients with migraine, nine studies examined MRI neuroimaging alone in patients with migraine, and four studies contained adults with headache or migraine who underwent either MRI or CT. The majority of studies analyzed were retrospective or cross-sectional in nature, while four studies were prospective observational studies.

Dr. Evans and colleagues noted that neuroimaging for patients with suspected migraine is ordered for a variety of reasons, such as excluding conditions that aren’t migraine, diagnostic certainty, cognitive bias, practice workflow, medicolegal concerns, addressing patient and family anxiety, and addressing clinician anxiety. Neuroimaging also can be costly, they said, adding up to an estimated $1 billion annually according to one study, and can lead to additional testing from findings that may not be clinically significant.
 

Good advice, with caveats

In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, said that while he generally does not like broad guideline recommendations, the recommendation made by the American Headache Society to avoid neuroimaging in patients with a normal neurological examination without any atypical features and red flags “takes most of the important factors into consideration and will work almost all the time.” The recommendation made by consensus for specific considerations of neuroimaging was issued by top headache specialists in the United States who reviewed the data, and it is unlikely a patient with a migraine as diagnosed by the International Classification of Headache Disorders with a normal neurological examination would have a significant abnormality that would appear with imaging, Dr. Rapoport said.

“If everyone caring for migraine patients knew these recommendations, and used them unless the patients fit the exclusions mentioned, we would have more efficient clinical practice and save lots of money on unnecessary scanning,” he said.

However, Dr. Rapoport, clinical professor of neurology at the University of California, Los Angeles, founder of the New England Center for Headache, and past president of The International Headache Society, said that not all clinicians will be convinced by the American Headache Society’s recommendations.

“Various third parties often jump on society recommendations or guidelines and prevent smart clinicians from doing what they need to do when they want to disregard the recommendation or guideline,” he explained. “More importantly, if a physician feels the need to think out of the box and image a patient without a clear reason, and the patient cannot pay for the scan when a medical insurance company refuses to authorize it, there can be a bad result if the patient does not get the study.”

Dr. Rapoport noted that the guideline does not address situations where neuroimaging may not pick up conditions that lead to migraine, such as a subarachnoid or subdural hemorrhage, reversible cerebral vasoconstriction syndrome, or early aspects of low cerebrospinal fluid pressure syndrome. Anxiety on the part of the patient or the clinician is another area that can be addressed by future research, he said.

“If the clinician does a good job of explaining the odds of anything significant being found with a typical migraine history and normal examination, and the patient says [they] need an MRI with contrast to be sure, it will be difficult to dissuade them,” said Dr. Rapoport. “If you don’t order one, they will find a way to get one. If it is abnormal, you could be in trouble. Also, if the clinician has no good reason to do a scan but has anxiety about what is being missed, it will probably get done.”

There was no funding source for the guidelines. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, and consultancies for a variety of pharmaceutical companies, agencies, institutions, publishers, and other organizations.

Patients with suspected migraine and a normal neurological examination without any atypical features or red flags do not need an MRI or CT, according to recent updated recommendations in a guideline released by the American Headache Society.

Migraine with atypical features may require neuroimaging, according to the guideline. These include an unusual aura; change in clinical features; a first or worst migraine; a migraine that presents with brainstem aura, confusion, or motor manifestation; migraine accompaniments in later life; headaches that are side-locked or posttraumatic; and aura that presents without headache.
 

Assessing the evidence

The recommendation to avoid MRI or CT in otherwise neurologically normal patients with migraine carried a grade A recommendation from the American Headache Society, while the specific considerations for neuroimaging was based on consensus and carried a grade C recommendation, according to lead author Randolph W. Evans, MD, of the department of neurology at Baylor College of Medicine in Houston, and colleagues.

The recommendations, published in the journal Headache (2020 Feb;60(2):318-36), came from a systematic review of 23 studies of adults at least 18 years old who underwent MRI or CT during outpatient treatment for migraine between 1973 and 2018. Ten studies looked at CT neuroimaging in patients with migraine, nine studies examined MRI neuroimaging alone in patients with migraine, and four studies contained adults with headache or migraine who underwent either MRI or CT. The majority of studies analyzed were retrospective or cross-sectional in nature, while four studies were prospective observational studies.

Dr. Evans and colleagues noted that neuroimaging for patients with suspected migraine is ordered for a variety of reasons, such as excluding conditions that aren’t migraine, diagnostic certainty, cognitive bias, practice workflow, medicolegal concerns, addressing patient and family anxiety, and addressing clinician anxiety. Neuroimaging also can be costly, they said, adding up to an estimated $1 billion annually according to one study, and can lead to additional testing from findings that may not be clinically significant.
 

Good advice, with caveats

In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, said that while he generally does not like broad guideline recommendations, the recommendation made by the American Headache Society to avoid neuroimaging in patients with a normal neurological examination without any atypical features and red flags “takes most of the important factors into consideration and will work almost all the time.” The recommendation made by consensus for specific considerations of neuroimaging was issued by top headache specialists in the United States who reviewed the data, and it is unlikely a patient with a migraine as diagnosed by the International Classification of Headache Disorders with a normal neurological examination would have a significant abnormality that would appear with imaging, Dr. Rapoport said.

“If everyone caring for migraine patients knew these recommendations, and used them unless the patients fit the exclusions mentioned, we would have more efficient clinical practice and save lots of money on unnecessary scanning,” he said.

However, Dr. Rapoport, clinical professor of neurology at the University of California, Los Angeles, founder of the New England Center for Headache, and past president of The International Headache Society, said that not all clinicians will be convinced by the American Headache Society’s recommendations.

“Various third parties often jump on society recommendations or guidelines and prevent smart clinicians from doing what they need to do when they want to disregard the recommendation or guideline,” he explained. “More importantly, if a physician feels the need to think out of the box and image a patient without a clear reason, and the patient cannot pay for the scan when a medical insurance company refuses to authorize it, there can be a bad result if the patient does not get the study.”

Dr. Rapoport noted that the guideline does not address situations where neuroimaging may not pick up conditions that lead to migraine, such as a subarachnoid or subdural hemorrhage, reversible cerebral vasoconstriction syndrome, or early aspects of low cerebrospinal fluid pressure syndrome. Anxiety on the part of the patient or the clinician is another area that can be addressed by future research, he said.

“If the clinician does a good job of explaining the odds of anything significant being found with a typical migraine history and normal examination, and the patient says [they] need an MRI with contrast to be sure, it will be difficult to dissuade them,” said Dr. Rapoport. “If you don’t order one, they will find a way to get one. If it is abnormal, you could be in trouble. Also, if the clinician has no good reason to do a scan but has anxiety about what is being missed, it will probably get done.”

There was no funding source for the guidelines. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, and consultancies for a variety of pharmaceutical companies, agencies, institutions, publishers, and other organizations.

Patients with suspected migraine and a normal neurological examination without any atypical features or red flags do not need an MRI or CT, according to recent updated recommendations in a guideline released by the American Headache Society.

Migraine with atypical features may require neuroimaging, according to the guideline. These include an unusual aura; change in clinical features; a first or worst migraine; a migraine that presents with brainstem aura, confusion, or motor manifestation; migraine accompaniments in later life; headaches that are side-locked or posttraumatic; and aura that presents without headache.
 

Assessing the evidence

The recommendation to avoid MRI or CT in otherwise neurologically normal patients with migraine carried a grade A recommendation from the American Headache Society, while the specific considerations for neuroimaging was based on consensus and carried a grade C recommendation, according to lead author Randolph W. Evans, MD, of the department of neurology at Baylor College of Medicine in Houston, and colleagues.

The recommendations, published in the journal Headache (2020 Feb;60(2):318-36), came from a systematic review of 23 studies of adults at least 18 years old who underwent MRI or CT during outpatient treatment for migraine between 1973 and 2018. Ten studies looked at CT neuroimaging in patients with migraine, nine studies examined MRI neuroimaging alone in patients with migraine, and four studies contained adults with headache or migraine who underwent either MRI or CT. The majority of studies analyzed were retrospective or cross-sectional in nature, while four studies were prospective observational studies.

Dr. Evans and colleagues noted that neuroimaging for patients with suspected migraine is ordered for a variety of reasons, such as excluding conditions that aren’t migraine, diagnostic certainty, cognitive bias, practice workflow, medicolegal concerns, addressing patient and family anxiety, and addressing clinician anxiety. Neuroimaging also can be costly, they said, adding up to an estimated $1 billion annually according to one study, and can lead to additional testing from findings that may not be clinically significant.
 

Good advice, with caveats

In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, said that while he generally does not like broad guideline recommendations, the recommendation made by the American Headache Society to avoid neuroimaging in patients with a normal neurological examination without any atypical features and red flags “takes most of the important factors into consideration and will work almost all the time.” The recommendation made by consensus for specific considerations of neuroimaging was issued by top headache specialists in the United States who reviewed the data, and it is unlikely a patient with a migraine as diagnosed by the International Classification of Headache Disorders with a normal neurological examination would have a significant abnormality that would appear with imaging, Dr. Rapoport said.

“If everyone caring for migraine patients knew these recommendations, and used them unless the patients fit the exclusions mentioned, we would have more efficient clinical practice and save lots of money on unnecessary scanning,” he said.

However, Dr. Rapoport, clinical professor of neurology at the University of California, Los Angeles, founder of the New England Center for Headache, and past president of The International Headache Society, said that not all clinicians will be convinced by the American Headache Society’s recommendations.

“Various third parties often jump on society recommendations or guidelines and prevent smart clinicians from doing what they need to do when they want to disregard the recommendation or guideline,” he explained. “More importantly, if a physician feels the need to think out of the box and image a patient without a clear reason, and the patient cannot pay for the scan when a medical insurance company refuses to authorize it, there can be a bad result if the patient does not get the study.”

Dr. Rapoport noted that the guideline does not address situations where neuroimaging may not pick up conditions that lead to migraine, such as a subarachnoid or subdural hemorrhage, reversible cerebral vasoconstriction syndrome, or early aspects of low cerebrospinal fluid pressure syndrome. Anxiety on the part of the patient or the clinician is another area that can be addressed by future research, he said.

“If the clinician does a good job of explaining the odds of anything significant being found with a typical migraine history and normal examination, and the patient says [they] need an MRI with contrast to be sure, it will be difficult to dissuade them,” said Dr. Rapoport. “If you don’t order one, they will find a way to get one. If it is abnormal, you could be in trouble. Also, if the clinician has no good reason to do a scan but has anxiety about what is being missed, it will probably get done.”

There was no funding source for the guidelines. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, and consultancies for a variety of pharmaceutical companies, agencies, institutions, publishers, and other organizations.