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AGA Guideline: Acute liver failure
Physicians should avoid routinely testing patients with acute liver failure for Wilson’s disease unless there is “high clinical suspicion” for the disorder, according to a new guideline from the AGA Institute.
Wilson’s disease so rarely accompanies acute liver failure that a positive test will have low predictive value, Steven L. Flamm, MD, of Northwestern University, Chicago, and his associates wrote in the February issue of Gastroenterology (doi: 10.1053/j.gastro.2016.12.026). Diagnosing Wilson’s disease also is unlikely to change treatment “because liver transplantation is the ultimate outcome,” they emphasize.
The guideline grades seven recommendations as “conditional” based on “very-low” quality evidence. These include the statement on Wilson’s disease testing, plus suggestions to test and treat patients with ALF for herpes simplex virus (HSV) infection, to test pregnant patients for hepatitis E virus infection, and to perform autoantibody testing for autoimmune hepatitis. Case series report only about a 1% prevalence of HSV infection in ALF, and there is little information on diagnostic accuracy or treatment in this setting, the guidelines state. Although acyclovir is relatively safe and inexpensive, data on efficacy is limited to “a suggestion on a case-report level that patients with acute hepatitis secondary to HSV do better with treatment than without.”
The guideline also conditionally recommends against routine testing for varicella zoster virus infection and routine liver biopsy in ALF. The authors note only about 10 case reports of varicella zoster–associated ALF and few data on how liver biopsy results in ALF alter treatment plan, outcome, or the choice to seek liver transplantation. The experts do recommend prognostic scoring with Model for End-Stage Liver Disease, which pooled analyses have found to be more sensitive than King’s College Criteria, they wrote.
The guideline conditionally recommends against empirically treating elevated intracranial pressure in ALF, on the basis of five randomized trials that found no overall mortality benefit of moderate hypothermia, hypertonic saline, L-ornithine, L-aspartate, intravenous mannitol, or hyperventilation.
The experts cite insufficient evidence to recommend using N-acetyl cysteine in patients whose ALF is not associated with acetaminophen exposure. Likewise, they find inadequate data to make any recommendation about using extracorporeal liver support systems outside of the setting of clinical trials. Although such systems can “potentially” buy time for patients to either spontaneously recover without transplant or survive longer on the transplantation list, three systematic reviews found “no clear effect on mortality,” and randomized trials reported either null results or a “marginally significant survival benefit” in the face of steep costs and potentially significant toxicities, the authors emphasize.
None of the experts had relevant financial disclosures.
Physicians should avoid routinely testing patients with acute liver failure for Wilson’s disease unless there is “high clinical suspicion” for the disorder, according to a new guideline from the AGA Institute.
Wilson’s disease so rarely accompanies acute liver failure that a positive test will have low predictive value, Steven L. Flamm, MD, of Northwestern University, Chicago, and his associates wrote in the February issue of Gastroenterology (doi: 10.1053/j.gastro.2016.12.026). Diagnosing Wilson’s disease also is unlikely to change treatment “because liver transplantation is the ultimate outcome,” they emphasize.
The guideline grades seven recommendations as “conditional” based on “very-low” quality evidence. These include the statement on Wilson’s disease testing, plus suggestions to test and treat patients with ALF for herpes simplex virus (HSV) infection, to test pregnant patients for hepatitis E virus infection, and to perform autoantibody testing for autoimmune hepatitis. Case series report only about a 1% prevalence of HSV infection in ALF, and there is little information on diagnostic accuracy or treatment in this setting, the guidelines state. Although acyclovir is relatively safe and inexpensive, data on efficacy is limited to “a suggestion on a case-report level that patients with acute hepatitis secondary to HSV do better with treatment than without.”
The guideline also conditionally recommends against routine testing for varicella zoster virus infection and routine liver biopsy in ALF. The authors note only about 10 case reports of varicella zoster–associated ALF and few data on how liver biopsy results in ALF alter treatment plan, outcome, or the choice to seek liver transplantation. The experts do recommend prognostic scoring with Model for End-Stage Liver Disease, which pooled analyses have found to be more sensitive than King’s College Criteria, they wrote.
The guideline conditionally recommends against empirically treating elevated intracranial pressure in ALF, on the basis of five randomized trials that found no overall mortality benefit of moderate hypothermia, hypertonic saline, L-ornithine, L-aspartate, intravenous mannitol, or hyperventilation.
The experts cite insufficient evidence to recommend using N-acetyl cysteine in patients whose ALF is not associated with acetaminophen exposure. Likewise, they find inadequate data to make any recommendation about using extracorporeal liver support systems outside of the setting of clinical trials. Although such systems can “potentially” buy time for patients to either spontaneously recover without transplant or survive longer on the transplantation list, three systematic reviews found “no clear effect on mortality,” and randomized trials reported either null results or a “marginally significant survival benefit” in the face of steep costs and potentially significant toxicities, the authors emphasize.
None of the experts had relevant financial disclosures.
Physicians should avoid routinely testing patients with acute liver failure for Wilson’s disease unless there is “high clinical suspicion” for the disorder, according to a new guideline from the AGA Institute.
Wilson’s disease so rarely accompanies acute liver failure that a positive test will have low predictive value, Steven L. Flamm, MD, of Northwestern University, Chicago, and his associates wrote in the February issue of Gastroenterology (doi: 10.1053/j.gastro.2016.12.026). Diagnosing Wilson’s disease also is unlikely to change treatment “because liver transplantation is the ultimate outcome,” they emphasize.
The guideline grades seven recommendations as “conditional” based on “very-low” quality evidence. These include the statement on Wilson’s disease testing, plus suggestions to test and treat patients with ALF for herpes simplex virus (HSV) infection, to test pregnant patients for hepatitis E virus infection, and to perform autoantibody testing for autoimmune hepatitis. Case series report only about a 1% prevalence of HSV infection in ALF, and there is little information on diagnostic accuracy or treatment in this setting, the guidelines state. Although acyclovir is relatively safe and inexpensive, data on efficacy is limited to “a suggestion on a case-report level that patients with acute hepatitis secondary to HSV do better with treatment than without.”
The guideline also conditionally recommends against routine testing for varicella zoster virus infection and routine liver biopsy in ALF. The authors note only about 10 case reports of varicella zoster–associated ALF and few data on how liver biopsy results in ALF alter treatment plan, outcome, or the choice to seek liver transplantation. The experts do recommend prognostic scoring with Model for End-Stage Liver Disease, which pooled analyses have found to be more sensitive than King’s College Criteria, they wrote.
The guideline conditionally recommends against empirically treating elevated intracranial pressure in ALF, on the basis of five randomized trials that found no overall mortality benefit of moderate hypothermia, hypertonic saline, L-ornithine, L-aspartate, intravenous mannitol, or hyperventilation.
The experts cite insufficient evidence to recommend using N-acetyl cysteine in patients whose ALF is not associated with acetaminophen exposure. Likewise, they find inadequate data to make any recommendation about using extracorporeal liver support systems outside of the setting of clinical trials. Although such systems can “potentially” buy time for patients to either spontaneously recover without transplant or survive longer on the transplantation list, three systematic reviews found “no clear effect on mortality,” and randomized trials reported either null results or a “marginally significant survival benefit” in the face of steep costs and potentially significant toxicities, the authors emphasize.
None of the experts had relevant financial disclosures.
FROM GASTROENTEROLOGY
Trump nominates Neil Gorsuch as 9th Supreme Court justice
President Donald Trump has chosen Neil Gorsuch, a conservative judge who presides over Denver’s 10th Circuit as his nominee for U.S. Supreme Court justice. A federal judge for 10 years, Judge Gorsuch is a long-time comrade of deceased Supreme Court Justice Antonin Scalia with a strong record of supporting religious freedom and less government control.
At a White House East Room ceremony on Jan. 31, Judge Gorsuch said he was honored and humbled by President’s Trump’s nomination and that he looked forward to answering questions during his Senate nomination hearing.
President Trump hailed Judge Gorsuch’s credentials as the “best he has ever seen,” and called him more than qualified to take the reins as the next Supreme Court justice.
“He has an extraordinary resume, as good as it gets,” President Trump said. “The qualifications of Judge Gorsuch are beyond dispute. He is a man of our country and a man who our country needs – and needs badly – to uphold the rule of law and the rule of justice.”
Judge Gorsuch, 49,was appointed to the 10th U.S. Circuit Court of Appeals in Denver, by President George W. Bush. His nomination was confirmed unanimously in the Senate. He holds a doctoral degree from Oxford University, (England), a law degree from Harvard Law School, Cambridge, Mass., and an undergraduate degree from Columbia University, New York. Judge Gorsuch began his legal career as a law clerk to Supreme Court justices Byron R. White and Anthony M. Kennedy, as well as to Judge David B. Sentelle of the U.S. Court of Appeals for the D.C. Circuit. Prior to his judicial appointment, Judge Gorsuch served as principal deputy associate attorney general at the Justice Department under George W. Bush.
A Senate confirmation hearing had not been announced at press time. Judge Gorsuch has pledged to work with both parties during the hearing to answer questions and alleviate any concerns.
“I look forward to speaking with members from both sides of the aisle,” he said. “I consider the United States Senate the greatest deliberative body in the world, and I respect the important role the Constitution affords it in the confirmation of our judges.”
Justice Antonin Scalia died suddenly on Feb. 13, 2016, leaving the high court with only eight members. Then-President Barack Obama nominated Judge Merrick Garland of the U.S. Court of Appeals for the District of Columbia Circuit to fill Scalia’s seat. However, the Republican-controlled Senate blocked Judge Garland from ever having a hearing and his nomination was never fully considered.
agallegos@frontlinemedcom.com
On Twitter @legal_med
President Donald Trump has chosen Neil Gorsuch, a conservative judge who presides over Denver’s 10th Circuit as his nominee for U.S. Supreme Court justice. A federal judge for 10 years, Judge Gorsuch is a long-time comrade of deceased Supreme Court Justice Antonin Scalia with a strong record of supporting religious freedom and less government control.
At a White House East Room ceremony on Jan. 31, Judge Gorsuch said he was honored and humbled by President’s Trump’s nomination and that he looked forward to answering questions during his Senate nomination hearing.
President Trump hailed Judge Gorsuch’s credentials as the “best he has ever seen,” and called him more than qualified to take the reins as the next Supreme Court justice.
“He has an extraordinary resume, as good as it gets,” President Trump said. “The qualifications of Judge Gorsuch are beyond dispute. He is a man of our country and a man who our country needs – and needs badly – to uphold the rule of law and the rule of justice.”
Judge Gorsuch, 49,was appointed to the 10th U.S. Circuit Court of Appeals in Denver, by President George W. Bush. His nomination was confirmed unanimously in the Senate. He holds a doctoral degree from Oxford University, (England), a law degree from Harvard Law School, Cambridge, Mass., and an undergraduate degree from Columbia University, New York. Judge Gorsuch began his legal career as a law clerk to Supreme Court justices Byron R. White and Anthony M. Kennedy, as well as to Judge David B. Sentelle of the U.S. Court of Appeals for the D.C. Circuit. Prior to his judicial appointment, Judge Gorsuch served as principal deputy associate attorney general at the Justice Department under George W. Bush.
A Senate confirmation hearing had not been announced at press time. Judge Gorsuch has pledged to work with both parties during the hearing to answer questions and alleviate any concerns.
“I look forward to speaking with members from both sides of the aisle,” he said. “I consider the United States Senate the greatest deliberative body in the world, and I respect the important role the Constitution affords it in the confirmation of our judges.”
Justice Antonin Scalia died suddenly on Feb. 13, 2016, leaving the high court with only eight members. Then-President Barack Obama nominated Judge Merrick Garland of the U.S. Court of Appeals for the District of Columbia Circuit to fill Scalia’s seat. However, the Republican-controlled Senate blocked Judge Garland from ever having a hearing and his nomination was never fully considered.
agallegos@frontlinemedcom.com
On Twitter @legal_med
President Donald Trump has chosen Neil Gorsuch, a conservative judge who presides over Denver’s 10th Circuit as his nominee for U.S. Supreme Court justice. A federal judge for 10 years, Judge Gorsuch is a long-time comrade of deceased Supreme Court Justice Antonin Scalia with a strong record of supporting religious freedom and less government control.
At a White House East Room ceremony on Jan. 31, Judge Gorsuch said he was honored and humbled by President’s Trump’s nomination and that he looked forward to answering questions during his Senate nomination hearing.
President Trump hailed Judge Gorsuch’s credentials as the “best he has ever seen,” and called him more than qualified to take the reins as the next Supreme Court justice.
“He has an extraordinary resume, as good as it gets,” President Trump said. “The qualifications of Judge Gorsuch are beyond dispute. He is a man of our country and a man who our country needs – and needs badly – to uphold the rule of law and the rule of justice.”
Judge Gorsuch, 49,was appointed to the 10th U.S. Circuit Court of Appeals in Denver, by President George W. Bush. His nomination was confirmed unanimously in the Senate. He holds a doctoral degree from Oxford University, (England), a law degree from Harvard Law School, Cambridge, Mass., and an undergraduate degree from Columbia University, New York. Judge Gorsuch began his legal career as a law clerk to Supreme Court justices Byron R. White and Anthony M. Kennedy, as well as to Judge David B. Sentelle of the U.S. Court of Appeals for the D.C. Circuit. Prior to his judicial appointment, Judge Gorsuch served as principal deputy associate attorney general at the Justice Department under George W. Bush.
A Senate confirmation hearing had not been announced at press time. Judge Gorsuch has pledged to work with both parties during the hearing to answer questions and alleviate any concerns.
“I look forward to speaking with members from both sides of the aisle,” he said. “I consider the United States Senate the greatest deliberative body in the world, and I respect the important role the Constitution affords it in the confirmation of our judges.”
Justice Antonin Scalia died suddenly on Feb. 13, 2016, leaving the high court with only eight members. Then-President Barack Obama nominated Judge Merrick Garland of the U.S. Court of Appeals for the District of Columbia Circuit to fill Scalia’s seat. However, the Republican-controlled Senate blocked Judge Garland from ever having a hearing and his nomination was never fully considered.
agallegos@frontlinemedcom.com
On Twitter @legal_med
VIDEO: Don’t miss reservoirs when treating recurrent onychomycosis
WAILEA, HAWAII – Patients attribute every nail problem to nail fungus, but part of the problem with nails is concomitant tinea pedis, tinea corporis, and other reservoirs of infection, according to Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego.
Failure to locate and treat these other reservoirs can lead to recurrence of the nail infection, Dr. Bhatia said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“If we aren’t treating the skin as well as the nails, it is creating a reservoir effect that reaccumulates in the nail itself,” he said. Similarly, the nails can serve as a reservoir of infection for the skin.
“That makes it all the more important” to treat both skin and nails and “treat through the disease state,” he commented in a video interview. Cost can influence treatment decisions, and there is a role for both topical and systemic therapy, he said. However, “if there’s not adequate testing or if there’s not a good proof of the diagnosis, we are just losing out no matter what we use,” he cautioned.
Dr. Bhatia disclosed relationships with companies including Actavis, Aqua, Allergan, Anacor, Bayer, Biofrontera, Biopharmx, Dermira, Dusa, Exceltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, Leo, Novartis, Sanofi, and Valeant.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – Patients attribute every nail problem to nail fungus, but part of the problem with nails is concomitant tinea pedis, tinea corporis, and other reservoirs of infection, according to Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego.
Failure to locate and treat these other reservoirs can lead to recurrence of the nail infection, Dr. Bhatia said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“If we aren’t treating the skin as well as the nails, it is creating a reservoir effect that reaccumulates in the nail itself,” he said. Similarly, the nails can serve as a reservoir of infection for the skin.
“That makes it all the more important” to treat both skin and nails and “treat through the disease state,” he commented in a video interview. Cost can influence treatment decisions, and there is a role for both topical and systemic therapy, he said. However, “if there’s not adequate testing or if there’s not a good proof of the diagnosis, we are just losing out no matter what we use,” he cautioned.
Dr. Bhatia disclosed relationships with companies including Actavis, Aqua, Allergan, Anacor, Bayer, Biofrontera, Biopharmx, Dermira, Dusa, Exceltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, Leo, Novartis, Sanofi, and Valeant.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – Patients attribute every nail problem to nail fungus, but part of the problem with nails is concomitant tinea pedis, tinea corporis, and other reservoirs of infection, according to Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego.
Failure to locate and treat these other reservoirs can lead to recurrence of the nail infection, Dr. Bhatia said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“If we aren’t treating the skin as well as the nails, it is creating a reservoir effect that reaccumulates in the nail itself,” he said. Similarly, the nails can serve as a reservoir of infection for the skin.
“That makes it all the more important” to treat both skin and nails and “treat through the disease state,” he commented in a video interview. Cost can influence treatment decisions, and there is a role for both topical and systemic therapy, he said. However, “if there’s not adequate testing or if there’s not a good proof of the diagnosis, we are just losing out no matter what we use,” he cautioned.
Dr. Bhatia disclosed relationships with companies including Actavis, Aqua, Allergan, Anacor, Bayer, Biofrontera, Biopharmx, Dermira, Dusa, Exceltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, Leo, Novartis, Sanofi, and Valeant.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF HAWAII DERMATOLOGY SEMINAR
Dems force delay in vote for HHS secretary
Democrats on the Senate Finance Committee forced a delay action that would have moved the nomination of Rep. Tom Price (R-Ga.) to the Senate floor for consideration, citing ongoing concerns with stock purchases made by Rep. Price.
The vote on Rep. Price’s nomination to serve as secretary of Health and Human Services was scheduled for Jan. 31, but all committee Democrats boycotted the executive session, forcing the delay. Committee rules state that at least 13 members, including at least 1 voting member from the minority party, must be present for a vote to proceed. The 26-member panel is made up of 14 Republicans and 12 Democrats.
“I asked Congressman Price [at his confirmation hearing] directly if he got an exclusive discount on stock in an Australian biomedical firm, and he said no,” Sen. Ron Wyden (D-Ore.), the committee’s leading Democrat, said in a statement. “From the committee’s investigation to company documents to the company official’s own words, the evidence tells a different story. It looks more and more like Congressman Price got special access to a special deal.
“The Finance Committee needs to continue following its bipartisan vetting process that has been upheld for more than 20 years. This is about getting answers to questions, plain and simple. Ethics laws are not optional, and nominees do not have a right to treat disclosures like a shell game,” Sen Wyden said.
At the confirmation hearing, Rep. Price, who is a retired orthopedic surgeon, asserted that he did not violate any ethics laws related to his purchase of Innate stock. He reaffirmed those thoughts in written answers to questions from committee members, stating that throughout “my time as a member of the U.S. House of Representatives, I have abided by and adhered to all ethics and conflicts of interest rules applicable to me.”
Committee Chairman Orrin Hatch (R-Utah) criticized Democrats for their boycott.
The committee was also scheduled to vote on Steve Mnuchin, President Trump’s nominee for Secretary of the Treasury. “Assuming that they can’t support these two, then they can vote against them,” Sen. Hatch said during the open session. “That’s what really an honest approach to this matter would be.”
At press time, a vote on Rep. Price has not been rescheduled, but Sen. Hatch noted that “I am hopeful when we schedule this again, they’ll be here.”
Democrats on the Senate Finance Committee forced a delay action that would have moved the nomination of Rep. Tom Price (R-Ga.) to the Senate floor for consideration, citing ongoing concerns with stock purchases made by Rep. Price.
The vote on Rep. Price’s nomination to serve as secretary of Health and Human Services was scheduled for Jan. 31, but all committee Democrats boycotted the executive session, forcing the delay. Committee rules state that at least 13 members, including at least 1 voting member from the minority party, must be present for a vote to proceed. The 26-member panel is made up of 14 Republicans and 12 Democrats.
“I asked Congressman Price [at his confirmation hearing] directly if he got an exclusive discount on stock in an Australian biomedical firm, and he said no,” Sen. Ron Wyden (D-Ore.), the committee’s leading Democrat, said in a statement. “From the committee’s investigation to company documents to the company official’s own words, the evidence tells a different story. It looks more and more like Congressman Price got special access to a special deal.
“The Finance Committee needs to continue following its bipartisan vetting process that has been upheld for more than 20 years. This is about getting answers to questions, plain and simple. Ethics laws are not optional, and nominees do not have a right to treat disclosures like a shell game,” Sen Wyden said.
At the confirmation hearing, Rep. Price, who is a retired orthopedic surgeon, asserted that he did not violate any ethics laws related to his purchase of Innate stock. He reaffirmed those thoughts in written answers to questions from committee members, stating that throughout “my time as a member of the U.S. House of Representatives, I have abided by and adhered to all ethics and conflicts of interest rules applicable to me.”
Committee Chairman Orrin Hatch (R-Utah) criticized Democrats for their boycott.
The committee was also scheduled to vote on Steve Mnuchin, President Trump’s nominee for Secretary of the Treasury. “Assuming that they can’t support these two, then they can vote against them,” Sen. Hatch said during the open session. “That’s what really an honest approach to this matter would be.”
At press time, a vote on Rep. Price has not been rescheduled, but Sen. Hatch noted that “I am hopeful when we schedule this again, they’ll be here.”
Democrats on the Senate Finance Committee forced a delay action that would have moved the nomination of Rep. Tom Price (R-Ga.) to the Senate floor for consideration, citing ongoing concerns with stock purchases made by Rep. Price.
The vote on Rep. Price’s nomination to serve as secretary of Health and Human Services was scheduled for Jan. 31, but all committee Democrats boycotted the executive session, forcing the delay. Committee rules state that at least 13 members, including at least 1 voting member from the minority party, must be present for a vote to proceed. The 26-member panel is made up of 14 Republicans and 12 Democrats.
“I asked Congressman Price [at his confirmation hearing] directly if he got an exclusive discount on stock in an Australian biomedical firm, and he said no,” Sen. Ron Wyden (D-Ore.), the committee’s leading Democrat, said in a statement. “From the committee’s investigation to company documents to the company official’s own words, the evidence tells a different story. It looks more and more like Congressman Price got special access to a special deal.
“The Finance Committee needs to continue following its bipartisan vetting process that has been upheld for more than 20 years. This is about getting answers to questions, plain and simple. Ethics laws are not optional, and nominees do not have a right to treat disclosures like a shell game,” Sen Wyden said.
At the confirmation hearing, Rep. Price, who is a retired orthopedic surgeon, asserted that he did not violate any ethics laws related to his purchase of Innate stock. He reaffirmed those thoughts in written answers to questions from committee members, stating that throughout “my time as a member of the U.S. House of Representatives, I have abided by and adhered to all ethics and conflicts of interest rules applicable to me.”
Committee Chairman Orrin Hatch (R-Utah) criticized Democrats for their boycott.
The committee was also scheduled to vote on Steve Mnuchin, President Trump’s nominee for Secretary of the Treasury. “Assuming that they can’t support these two, then they can vote against them,” Sen. Hatch said during the open session. “That’s what really an honest approach to this matter would be.”
At press time, a vote on Rep. Price has not been rescheduled, but Sen. Hatch noted that “I am hopeful when we schedule this again, they’ll be here.”
VIDEO: Consider PPIs as a cause of cutaneous reactions
WAILEA, HAWAII – Any proton pump inhibitor (PPI) has the potential to cause skin reactions, so it is important to ask patients about their use, according to J. Mark Jackson, MD, of the University of Louisville (Ky.).
If patients are going to react to a PPI, they usually will do so within 3 or 4 months of starting treatment, rather than in the first week or so of treatment, Dr. Jackson said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Skin reactions to PPIs are often maculopapular, with a flat and a raised component that can be nonspecific, Dr. Jackson noted.
Interestingly, he added, many times patients can switch to a different PPI and not get a skin reaction. However, there are some patients who develop a lupuslike reaction on the skin, and in these cases, there tends to be cross reactivity, “so they couldn’t switch to a different PPI and be risk-free” of the same reaction, he noted.
Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – Any proton pump inhibitor (PPI) has the potential to cause skin reactions, so it is important to ask patients about their use, according to J. Mark Jackson, MD, of the University of Louisville (Ky.).
If patients are going to react to a PPI, they usually will do so within 3 or 4 months of starting treatment, rather than in the first week or so of treatment, Dr. Jackson said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Skin reactions to PPIs are often maculopapular, with a flat and a raised component that can be nonspecific, Dr. Jackson noted.
Interestingly, he added, many times patients can switch to a different PPI and not get a skin reaction. However, there are some patients who develop a lupuslike reaction on the skin, and in these cases, there tends to be cross reactivity, “so they couldn’t switch to a different PPI and be risk-free” of the same reaction, he noted.
Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – Any proton pump inhibitor (PPI) has the potential to cause skin reactions, so it is important to ask patients about their use, according to J. Mark Jackson, MD, of the University of Louisville (Ky.).
If patients are going to react to a PPI, they usually will do so within 3 or 4 months of starting treatment, rather than in the first week or so of treatment, Dr. Jackson said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Skin reactions to PPIs are often maculopapular, with a flat and a raised component that can be nonspecific, Dr. Jackson noted.
Interestingly, he added, many times patients can switch to a different PPI and not get a skin reaction. However, there are some patients who develop a lupuslike reaction on the skin, and in these cases, there tends to be cross reactivity, “so they couldn’t switch to a different PPI and be risk-free” of the same reaction, he noted.
Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF HAWAII DERMATOLOGY SEMINAR
VIDEO: Experts offer patch testing tips for AD patients
WAILEA, HAWAII – Many atopic dermatitis patients with refractory disease may have also developed allergic contact dermatitis, according to Jonathan Silverberg, MD, of Northwestern University in Chicago.
Clinically, there is often overlap between AD and allergic contact dermatitis, said Dr. Silverberg, who was involved in the development of recent consensus guidelines on when to do patch testing in the setting of AD.
For many patients with severe disease, “sometimes when we patch test, we can find a relevant allergen for the patient to avoid, [and] within a few months, their disease just goes down a notch, gets much better, and really starts to respond to topical and more conservative approaches,” Dr. Silverberg said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. Or patients may respond well to AD treatment on certain parts of the body, but there may be other areas that don’t respond as well, suggesting a possible component of allergic contact dermatitis, he added
The guidelines sought to sort out scenarios “where it makes sense to patch test” and to provide direction on best practices, noted Dr. Silverberg, who is director of the Northwestern Medicine Multidisciplinary Eczema Center, and director of the patch testing clinic, Northwestern Memorial Hospital, Chicago.
He disclosed relationships with companies including AbbVie, Anacor, Celgene, Chugai, GlaxoSmithKline, Lilly, MedImmune-AstraZeneca, Pfizer, Procter & Gamble, Puricore, and Regeneron-Sanofi.SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – Many atopic dermatitis patients with refractory disease may have also developed allergic contact dermatitis, according to Jonathan Silverberg, MD, of Northwestern University in Chicago.
Clinically, there is often overlap between AD and allergic contact dermatitis, said Dr. Silverberg, who was involved in the development of recent consensus guidelines on when to do patch testing in the setting of AD.
For many patients with severe disease, “sometimes when we patch test, we can find a relevant allergen for the patient to avoid, [and] within a few months, their disease just goes down a notch, gets much better, and really starts to respond to topical and more conservative approaches,” Dr. Silverberg said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. Or patients may respond well to AD treatment on certain parts of the body, but there may be other areas that don’t respond as well, suggesting a possible component of allergic contact dermatitis, he added
The guidelines sought to sort out scenarios “where it makes sense to patch test” and to provide direction on best practices, noted Dr. Silverberg, who is director of the Northwestern Medicine Multidisciplinary Eczema Center, and director of the patch testing clinic, Northwestern Memorial Hospital, Chicago.
He disclosed relationships with companies including AbbVie, Anacor, Celgene, Chugai, GlaxoSmithKline, Lilly, MedImmune-AstraZeneca, Pfizer, Procter & Gamble, Puricore, and Regeneron-Sanofi.SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – Many atopic dermatitis patients with refractory disease may have also developed allergic contact dermatitis, according to Jonathan Silverberg, MD, of Northwestern University in Chicago.
Clinically, there is often overlap between AD and allergic contact dermatitis, said Dr. Silverberg, who was involved in the development of recent consensus guidelines on when to do patch testing in the setting of AD.
For many patients with severe disease, “sometimes when we patch test, we can find a relevant allergen for the patient to avoid, [and] within a few months, their disease just goes down a notch, gets much better, and really starts to respond to topical and more conservative approaches,” Dr. Silverberg said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. Or patients may respond well to AD treatment on certain parts of the body, but there may be other areas that don’t respond as well, suggesting a possible component of allergic contact dermatitis, he added
The guidelines sought to sort out scenarios “where it makes sense to patch test” and to provide direction on best practices, noted Dr. Silverberg, who is director of the Northwestern Medicine Multidisciplinary Eczema Center, and director of the patch testing clinic, Northwestern Memorial Hospital, Chicago.
He disclosed relationships with companies including AbbVie, Anacor, Celgene, Chugai, GlaxoSmithKline, Lilly, MedImmune-AstraZeneca, Pfizer, Procter & Gamble, Puricore, and Regeneron-Sanofi.SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF HAWAII DERMATOLOGY SEMINAR
VIDEO: Dermatologists often miss adult onset atopic dermatitis
WAILEA, HAWAII – Evidence from several recent studies suggests that the prevalence of adult onset atopic dermatitis in the United States may be as high as 7%-10%, said Jonathan I. Silverberg, MD, of the department of dermatology, preventive medicine, and medical social sciences, Northwestern University, Chicago.
Many features are similar to atopic dermatitis (AD) seen in childhood, but in adults the eczema is more likely to affect the hands and the eyelids. “We often have a hard time telling that apart from contact dermatitis,” Dr. Silverberg said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Some adults may have forgotten they had AD as children and don’t recognize it if it reappears in adulthood, but sometimes AD appears with no childhood history, he noted. “There’s a skepticism that if it is adult onset, it must not be atopic dermatitis,” but he has found that is not always the case.
A take-home message for clinicians: “Don’t be surprised when a patient walks in the door as an adult meeting all criteria for atopic dermatitis. It can be, and you can diagnose them comfortably,” said Dr. Silverberg, who is also director of the Northwestern Medicine Multidisciplinary Eczema Center, Northwestern Memorial Hospital, Chicago.
Most of the treatments for adult AD “cover many different arms of the immune system,” and include topical steroids and immunosuppressants, he added.
Dr. Silverberg disclosed relationships with companies including AbbVie, Anacor, Celgene, Chugai, GlaxoSmithKline, Lilly, MedImmune-AstraZeneca, Pfizer, Procter & Gamble, Puricore, and Regeneron-Sanofi. SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – Evidence from several recent studies suggests that the prevalence of adult onset atopic dermatitis in the United States may be as high as 7%-10%, said Jonathan I. Silverberg, MD, of the department of dermatology, preventive medicine, and medical social sciences, Northwestern University, Chicago.
Many features are similar to atopic dermatitis (AD) seen in childhood, but in adults the eczema is more likely to affect the hands and the eyelids. “We often have a hard time telling that apart from contact dermatitis,” Dr. Silverberg said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Some adults may have forgotten they had AD as children and don’t recognize it if it reappears in adulthood, but sometimes AD appears with no childhood history, he noted. “There’s a skepticism that if it is adult onset, it must not be atopic dermatitis,” but he has found that is not always the case.
A take-home message for clinicians: “Don’t be surprised when a patient walks in the door as an adult meeting all criteria for atopic dermatitis. It can be, and you can diagnose them comfortably,” said Dr. Silverberg, who is also director of the Northwestern Medicine Multidisciplinary Eczema Center, Northwestern Memorial Hospital, Chicago.
Most of the treatments for adult AD “cover many different arms of the immune system,” and include topical steroids and immunosuppressants, he added.
Dr. Silverberg disclosed relationships with companies including AbbVie, Anacor, Celgene, Chugai, GlaxoSmithKline, Lilly, MedImmune-AstraZeneca, Pfizer, Procter & Gamble, Puricore, and Regeneron-Sanofi. SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – Evidence from several recent studies suggests that the prevalence of adult onset atopic dermatitis in the United States may be as high as 7%-10%, said Jonathan I. Silverberg, MD, of the department of dermatology, preventive medicine, and medical social sciences, Northwestern University, Chicago.
Many features are similar to atopic dermatitis (AD) seen in childhood, but in adults the eczema is more likely to affect the hands and the eyelids. “We often have a hard time telling that apart from contact dermatitis,” Dr. Silverberg said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Some adults may have forgotten they had AD as children and don’t recognize it if it reappears in adulthood, but sometimes AD appears with no childhood history, he noted. “There’s a skepticism that if it is adult onset, it must not be atopic dermatitis,” but he has found that is not always the case.
A take-home message for clinicians: “Don’t be surprised when a patient walks in the door as an adult meeting all criteria for atopic dermatitis. It can be, and you can diagnose them comfortably,” said Dr. Silverberg, who is also director of the Northwestern Medicine Multidisciplinary Eczema Center, Northwestern Memorial Hospital, Chicago.
Most of the treatments for adult AD “cover many different arms of the immune system,” and include topical steroids and immunosuppressants, he added.
Dr. Silverberg disclosed relationships with companies including AbbVie, Anacor, Celgene, Chugai, GlaxoSmithKline, Lilly, MedImmune-AstraZeneca, Pfizer, Procter & Gamble, Puricore, and Regeneron-Sanofi. SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF HAWAII DERMATOLOGY SEMINAR
AAN Guideline Assesses fMRI for Presurgical Evaluation of Patients With Epilepsy
When preparing for epilepsy surgery, neurologists may consider using functional MRI (fMRI) instead of the intracarotid amobarbital procedure (IAP) to map language and memory functions in the brain, according to a practice guideline developed by the American Academy of Neurology (AAN). The current evidence is weak, however, and clinicians should advise patients carefully about the benefits and risks of IAP (also known as the Wada test) and fMRI, according to the guideline, which was published online ahead of print January 11 in Neurology.
IAP, an invasive technique, is the current standard for presurgical evaluation in epilepsy. fMRI is noninvasive and also considered safe. Neither of the two methods has been standardized. “Because fMRI is becoming more widely available, we wanted to see how it compares to the Wada test,” said lead author Jerzy Szaflarski, MD, PhD, Professor of Neurology at the University of Alabama at Birmingham. “While the risks associated with the Wada test are rare, they can be serious, including stroke and injury to the carotid artery.”
The AAN formed an 11-member panel to draft the guidelines. Two panelists independently selected 37 possibly relevant articles. Studies with fewer than 15 cases, case reports, meta-analyses, and editorials were excluded. Two panelists rated each article according to the AAN’s diagnostic and prognostic classification of evidence, and the panel ultimately developed consensus recommendations.
Data Support fMRI for Certain Situations
Class II data indicated that fMRI possibly provides language lateralization information concordant with that of IAP in 87% of people with medial temporal lobe epilepsy and in 81% of patients with extratemporal epilepsy. Current comparative data for temporal tumors or lateral temporal cases are insufficient to draw conclusions. Thus, fMRI may be considered as an option for lateralizing language functions in place of IAP in patients with medial temporal lobe epilepsy (Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C), said the authors. The evidence is unclear for patients with temporal neocortical epilepsy or temporal tumors (Level U).
One Class II study and one Class III study suggested that fMRI is possibly effective in aiding the prediction of postsurgical language deficits in patients undergoing presurgical evaluation for possible temporal lobectomy. The authors recommended that fMRI may be considered for predicting postsurgical language outcomes after anterior temporal lobe resection for the control of temporal lobe epilepsy (Level C).
Class II evidence suggests that in patients with medial temporal lobe epilepsy, fMRI is comparable with IAP in its ability to lateralize memory functions and may be used for this purpose. The authors recommended that fMRI may be considered as an option to lateralize memory functions in place of IAP in patients with medial temporal lobe epilepsy (Level C).
Nine Class II studies with different methods together suggested that fMRI leftward activation asymmetry during encoding of verbal material, regardless of whether measured in the medial temporal lobe or in the language network, probably predicts verbal memory decline after left medial temporal lobe surgery. The authors therefore recommended that presurgical fMRI of verbal memory or of language encoding should be considered as an option to predict verbal memory outcome in patients with epilepsy who are undergoing evaluation for left medial temporal lobe surgery (Level B).
A Class II study indicated that fMRI activation asymmetry during nonverbal (ie, scene and face recognition) memory tasks possibly predicts nonverbal memory decline after medial temporal lobe surgery. The authors recommended that presurgical fMRI using nonverbal memory encoding may be considered as a means to predict visuospatial memory outcomes in patients with epilepsy who are undergoing evaluation for temporal lobe surgery (Level C).
Based on data from one Class II study and one Class III study, the authors recommended that presurgical fMRI may be used instead of the IAP for language lateralization in patients with epilepsy who are undergoing evaluation for brain surgery (Level C). “However, when fMRI is used for this purpose, task design, data analysis methods, and epilepsy type should be considered,” they added.
In addition, based on nine Class II studies, the authors recommended that fMRI of language and verbal memory lateralization may be an alternative to IAP memory testing for prediction of verbal memory outcome in medial temporal lobe epilepsy (Level C). The authors note that fMRI is not yet established as an alternative to the IAP for prediction of global amnesia in patients who have undergone anterior temporal lobe surgery.
More and Larger Studies Are Needed
“The imperfect concordance between fMRI and IAP language lateralization leaves open the question of which test is more accurate in discordant cases,” said the authors. Although the IAP is the reference standard, it is subject to limitations resulting from individual variation in arterial anatomy, variable effects of anesthesia, the rate of amobarbital injection, variability in patient cooperation, and variation in testing methods.
Like the IAP, cognitive fMRI “is a complex diagnostic procedure that requires both advanced technical expertise in imaging and expert interaction with patients to elicit adequate levels of task performance, select a set of activation tasks appropriate to the patient’s ability and the clinical aims of the study, instruct the patient on the tasks, administer the tasks during scanning, and evaluate and provide corrective feedback on task performance during the scanning session,” said the authors.
Global amnesia may result from bilateral medial temporal lobe damage, and some neurologists depend on the IAP to evaluate a patient’s risk for this outcome. “Global amnesia is rare after unilateral temporal lobe surgery, however, and occurs mainly when there is preexisting contralateral medial temporal lobe dysfunction,” said the authors. “One possible approach, therefore, is to reserve use of the IAP memory test for those patients at greatest risk for global amnesia, that is, patients undergoing unilateral anterior temporal lobe resection who have structural or functional evidence of damage to the contralateral medial temporal lobe.”
“Larger studies need to be conducted to increase the quality of available evidence,” Dr. Szaflarski concluded.
—Erik Greb
Suggested Reading
Szaflarski JP, Gloss D, Binder JR, et al. Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy—Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 Jan 11 [Epub ahead of print].
When preparing for epilepsy surgery, neurologists may consider using functional MRI (fMRI) instead of the intracarotid amobarbital procedure (IAP) to map language and memory functions in the brain, according to a practice guideline developed by the American Academy of Neurology (AAN). The current evidence is weak, however, and clinicians should advise patients carefully about the benefits and risks of IAP (also known as the Wada test) and fMRI, according to the guideline, which was published online ahead of print January 11 in Neurology.
IAP, an invasive technique, is the current standard for presurgical evaluation in epilepsy. fMRI is noninvasive and also considered safe. Neither of the two methods has been standardized. “Because fMRI is becoming more widely available, we wanted to see how it compares to the Wada test,” said lead author Jerzy Szaflarski, MD, PhD, Professor of Neurology at the University of Alabama at Birmingham. “While the risks associated with the Wada test are rare, they can be serious, including stroke and injury to the carotid artery.”
The AAN formed an 11-member panel to draft the guidelines. Two panelists independently selected 37 possibly relevant articles. Studies with fewer than 15 cases, case reports, meta-analyses, and editorials were excluded. Two panelists rated each article according to the AAN’s diagnostic and prognostic classification of evidence, and the panel ultimately developed consensus recommendations.
Data Support fMRI for Certain Situations
Class II data indicated that fMRI possibly provides language lateralization information concordant with that of IAP in 87% of people with medial temporal lobe epilepsy and in 81% of patients with extratemporal epilepsy. Current comparative data for temporal tumors or lateral temporal cases are insufficient to draw conclusions. Thus, fMRI may be considered as an option for lateralizing language functions in place of IAP in patients with medial temporal lobe epilepsy (Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C), said the authors. The evidence is unclear for patients with temporal neocortical epilepsy or temporal tumors (Level U).
One Class II study and one Class III study suggested that fMRI is possibly effective in aiding the prediction of postsurgical language deficits in patients undergoing presurgical evaluation for possible temporal lobectomy. The authors recommended that fMRI may be considered for predicting postsurgical language outcomes after anterior temporal lobe resection for the control of temporal lobe epilepsy (Level C).
Class II evidence suggests that in patients with medial temporal lobe epilepsy, fMRI is comparable with IAP in its ability to lateralize memory functions and may be used for this purpose. The authors recommended that fMRI may be considered as an option to lateralize memory functions in place of IAP in patients with medial temporal lobe epilepsy (Level C).
Nine Class II studies with different methods together suggested that fMRI leftward activation asymmetry during encoding of verbal material, regardless of whether measured in the medial temporal lobe or in the language network, probably predicts verbal memory decline after left medial temporal lobe surgery. The authors therefore recommended that presurgical fMRI of verbal memory or of language encoding should be considered as an option to predict verbal memory outcome in patients with epilepsy who are undergoing evaluation for left medial temporal lobe surgery (Level B).
A Class II study indicated that fMRI activation asymmetry during nonverbal (ie, scene and face recognition) memory tasks possibly predicts nonverbal memory decline after medial temporal lobe surgery. The authors recommended that presurgical fMRI using nonverbal memory encoding may be considered as a means to predict visuospatial memory outcomes in patients with epilepsy who are undergoing evaluation for temporal lobe surgery (Level C).
Based on data from one Class II study and one Class III study, the authors recommended that presurgical fMRI may be used instead of the IAP for language lateralization in patients with epilepsy who are undergoing evaluation for brain surgery (Level C). “However, when fMRI is used for this purpose, task design, data analysis methods, and epilepsy type should be considered,” they added.
In addition, based on nine Class II studies, the authors recommended that fMRI of language and verbal memory lateralization may be an alternative to IAP memory testing for prediction of verbal memory outcome in medial temporal lobe epilepsy (Level C). The authors note that fMRI is not yet established as an alternative to the IAP for prediction of global amnesia in patients who have undergone anterior temporal lobe surgery.
More and Larger Studies Are Needed
“The imperfect concordance between fMRI and IAP language lateralization leaves open the question of which test is more accurate in discordant cases,” said the authors. Although the IAP is the reference standard, it is subject to limitations resulting from individual variation in arterial anatomy, variable effects of anesthesia, the rate of amobarbital injection, variability in patient cooperation, and variation in testing methods.
Like the IAP, cognitive fMRI “is a complex diagnostic procedure that requires both advanced technical expertise in imaging and expert interaction with patients to elicit adequate levels of task performance, select a set of activation tasks appropriate to the patient’s ability and the clinical aims of the study, instruct the patient on the tasks, administer the tasks during scanning, and evaluate and provide corrective feedback on task performance during the scanning session,” said the authors.
Global amnesia may result from bilateral medial temporal lobe damage, and some neurologists depend on the IAP to evaluate a patient’s risk for this outcome. “Global amnesia is rare after unilateral temporal lobe surgery, however, and occurs mainly when there is preexisting contralateral medial temporal lobe dysfunction,” said the authors. “One possible approach, therefore, is to reserve use of the IAP memory test for those patients at greatest risk for global amnesia, that is, patients undergoing unilateral anterior temporal lobe resection who have structural or functional evidence of damage to the contralateral medial temporal lobe.”
“Larger studies need to be conducted to increase the quality of available evidence,” Dr. Szaflarski concluded.
—Erik Greb
Suggested Reading
Szaflarski JP, Gloss D, Binder JR, et al. Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy—Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 Jan 11 [Epub ahead of print].
When preparing for epilepsy surgery, neurologists may consider using functional MRI (fMRI) instead of the intracarotid amobarbital procedure (IAP) to map language and memory functions in the brain, according to a practice guideline developed by the American Academy of Neurology (AAN). The current evidence is weak, however, and clinicians should advise patients carefully about the benefits and risks of IAP (also known as the Wada test) and fMRI, according to the guideline, which was published online ahead of print January 11 in Neurology.
IAP, an invasive technique, is the current standard for presurgical evaluation in epilepsy. fMRI is noninvasive and also considered safe. Neither of the two methods has been standardized. “Because fMRI is becoming more widely available, we wanted to see how it compares to the Wada test,” said lead author Jerzy Szaflarski, MD, PhD, Professor of Neurology at the University of Alabama at Birmingham. “While the risks associated with the Wada test are rare, they can be serious, including stroke and injury to the carotid artery.”
The AAN formed an 11-member panel to draft the guidelines. Two panelists independently selected 37 possibly relevant articles. Studies with fewer than 15 cases, case reports, meta-analyses, and editorials were excluded. Two panelists rated each article according to the AAN’s diagnostic and prognostic classification of evidence, and the panel ultimately developed consensus recommendations.
Data Support fMRI for Certain Situations
Class II data indicated that fMRI possibly provides language lateralization information concordant with that of IAP in 87% of people with medial temporal lobe epilepsy and in 81% of patients with extratemporal epilepsy. Current comparative data for temporal tumors or lateral temporal cases are insufficient to draw conclusions. Thus, fMRI may be considered as an option for lateralizing language functions in place of IAP in patients with medial temporal lobe epilepsy (Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C), said the authors. The evidence is unclear for patients with temporal neocortical epilepsy or temporal tumors (Level U).
One Class II study and one Class III study suggested that fMRI is possibly effective in aiding the prediction of postsurgical language deficits in patients undergoing presurgical evaluation for possible temporal lobectomy. The authors recommended that fMRI may be considered for predicting postsurgical language outcomes after anterior temporal lobe resection for the control of temporal lobe epilepsy (Level C).
Class II evidence suggests that in patients with medial temporal lobe epilepsy, fMRI is comparable with IAP in its ability to lateralize memory functions and may be used for this purpose. The authors recommended that fMRI may be considered as an option to lateralize memory functions in place of IAP in patients with medial temporal lobe epilepsy (Level C).
Nine Class II studies with different methods together suggested that fMRI leftward activation asymmetry during encoding of verbal material, regardless of whether measured in the medial temporal lobe or in the language network, probably predicts verbal memory decline after left medial temporal lobe surgery. The authors therefore recommended that presurgical fMRI of verbal memory or of language encoding should be considered as an option to predict verbal memory outcome in patients with epilepsy who are undergoing evaluation for left medial temporal lobe surgery (Level B).
A Class II study indicated that fMRI activation asymmetry during nonverbal (ie, scene and face recognition) memory tasks possibly predicts nonverbal memory decline after medial temporal lobe surgery. The authors recommended that presurgical fMRI using nonverbal memory encoding may be considered as a means to predict visuospatial memory outcomes in patients with epilepsy who are undergoing evaluation for temporal lobe surgery (Level C).
Based on data from one Class II study and one Class III study, the authors recommended that presurgical fMRI may be used instead of the IAP for language lateralization in patients with epilepsy who are undergoing evaluation for brain surgery (Level C). “However, when fMRI is used for this purpose, task design, data analysis methods, and epilepsy type should be considered,” they added.
In addition, based on nine Class II studies, the authors recommended that fMRI of language and verbal memory lateralization may be an alternative to IAP memory testing for prediction of verbal memory outcome in medial temporal lobe epilepsy (Level C). The authors note that fMRI is not yet established as an alternative to the IAP for prediction of global amnesia in patients who have undergone anterior temporal lobe surgery.
More and Larger Studies Are Needed
“The imperfect concordance between fMRI and IAP language lateralization leaves open the question of which test is more accurate in discordant cases,” said the authors. Although the IAP is the reference standard, it is subject to limitations resulting from individual variation in arterial anatomy, variable effects of anesthesia, the rate of amobarbital injection, variability in patient cooperation, and variation in testing methods.
Like the IAP, cognitive fMRI “is a complex diagnostic procedure that requires both advanced technical expertise in imaging and expert interaction with patients to elicit adequate levels of task performance, select a set of activation tasks appropriate to the patient’s ability and the clinical aims of the study, instruct the patient on the tasks, administer the tasks during scanning, and evaluate and provide corrective feedback on task performance during the scanning session,” said the authors.
Global amnesia may result from bilateral medial temporal lobe damage, and some neurologists depend on the IAP to evaluate a patient’s risk for this outcome. “Global amnesia is rare after unilateral temporal lobe surgery, however, and occurs mainly when there is preexisting contralateral medial temporal lobe dysfunction,” said the authors. “One possible approach, therefore, is to reserve use of the IAP memory test for those patients at greatest risk for global amnesia, that is, patients undergoing unilateral anterior temporal lobe resection who have structural or functional evidence of damage to the contralateral medial temporal lobe.”
“Larger studies need to be conducted to increase the quality of available evidence,” Dr. Szaflarski concluded.
—Erik Greb
Suggested Reading
Szaflarski JP, Gloss D, Binder JR, et al. Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy—Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 Jan 11 [Epub ahead of print].
What Are the Best Treatments for Nonmotor Symptoms in Parkinson’s Disease?
PORTLAND, OR—Nonmotor symptoms are common in patients with Parkinson’s disease and they can substantially impact quality of life, according to an overview presented at the Fourth World Parkinson Congress.
“Nonmotor symptoms in Parkinson’s disease have become increasingly recognized, and the number of clinical trials that are now out there is also on the increase,” said Susan H. Fox, MD, PhD, Associate Professor of Neurology at the University of Toronto.
Over the course of the illness, nonmotor symptoms become increasingly prevalent and are major determinants of the progression of overall disability. Conflicting evidence can make it difficult to choose appropriate treatments for some nonmotor symptoms such as depression and psychosis. Additionally, neurologists lack validated scales that accurately measure nonmotor symptoms, which further complicates treatment. Nevertheless, the literature does provide guidance for neurologists.
Managing Depression
Depression can affect as much as 60% of patients with Parkinson’s disease, according to the Parkinson’s Disease Foundation. Most interventions for depression have not been assessed extensively in patients with Parkinson’s disease, said Dr. Fox. Tricyclic antidepressants such as amitriptyline were evaluated in Parkinson’s disease, but study populations have been small, and the evidence has been conflicting. Other interventions for depression include selective serotonin reuptake inhibitors (SSRIs) such as citalopram, sertraline, paroxetine, and fluoxetine. Evidence for these drugs is considered insufficient.
A study of nortriptyline and paroxetine versus placebo found that nortriptyline significantly reduced depression, but that paroxetine did not. A follow-up study, however, comparing paroxetine to venlafaxine showed that paroxetine was effective in patients with Parkinson’s disease and depression.
Pramipexole, a dopamine agonist, may be an effective intervention for depression in Parkinson’s disease, according to Barone et al. Additionally, rasagiline, a monoamine oxidase-B inhibitor, has been tested in patients with Parkinson’s disease. Evidence suggests that rasagiline has a nonsignificant clinical effect on depression in these patients. Richard et al concluded that venlafaxine may be effective in this population. Their study did not identify any safety concerns. According to Dobkin et al, cognitive behavioral therapy may be an effective nonpharmacologic treatment for depression in Parkinson’s disease.
Cognitive Problems
Clinical trials so far have provided insufficient evidence about the efficacy of the acetylcholinesterase inhibitors donepezil and galantamine for treating cognitive impairment such as dementia in Parkinson’s disease. Studies do suggest, however, that rivastigmine promotes positive outcomes among patients with cognitive problems, but adverse events are common. Researchers compared oral and patch preparations of rivastigmine in a long-term open-label study that included a large number of patients. Fewer patients experienced tremor with the patch, compared with the oral formulation.
The data for memantine as an intervention for cognitive impairment in Parkinson’s disease are mixed. The drug is considered to have insufficient evidence. Exercise and cognitive behavioral therapy have also been studied for cognitive impairment, but experts have not developed evidence-based recommendations about these interventions.
Measuring Psychosis
Psychosis can cause significant morbidity in patients with Parkinson’s disease. Treating psychosis can be complicated because symptoms such as hallucinations, delusions, and paranoia may not persist. It may be difficult to determine whether the intervention reduced these psychotic symptoms or whether they resolved themselves, said Dr. Fox.
In addition, a lack of widely used validated scales makes measuring psychosis in Parkinson’s disease more difficult. Trials often have used rating scales borrowed from Alzheimer’s disease research. The difference between Alzheimer’s disease and Parkinson’s disease may bias the study results or cause researchers to overlook a drug that may provide benefit, said Dr. Fox.
Still, the literature does provide guidance. Overall, clozapine is considered effective in controlling psychosis in Parkinson’s disease. The associated risk of agranulocytosis makes this treatment less popular, however. As a result, some physicians avoid prescribing clozapine because it requires patients to undergo specialized blood monitoring.
Quetiapine may help to manage psychosis in Parkinson’s disease; most physicians would consider it a first-line agent for treating psychosis because of its ease of use, said Dr. Fox. However, insufficient evidence supports the drug’s use. Pimavanserin, a 5-HT2A inverse agonist, was recently approved for treatment of psychosis in Parkinson’s disease.
Other Nonmotor Symptoms
Autonomic dysfunctions such as overactive bladder syndrome, sialorrhoea, and constipation are also common nonmotor symptoms of Parkinson’s disease. Studies show that botulinum toxins are efficacious for treating sialorrhoea in Parkinson’s disease. Side effects such as dry mouth, transient swallowing difficulties, and severe dysphagia have been reported, although the latter is rare.
Lubiprostrone is considered likely efficacious for treating constipation in Parkinson’s disease. Researchers concluded that there is insufficient evidence for the drug’s safety in patients with Parkinson’s disease, however. Typical adverse events include nausea, diarrhea, and dyspnea.
When it comes to treating sleep disorders associated with Parkinson’s disease (eg, insomnia, excessive daytime somnolence, and sudden onset of sleep), there is insufficient evidence. Drugs such as melatonin and eszopiclone are not well studied in this population.
“I don’t think we fully understand the pathology or the cause of many nonmotor symptoms. Certainly we have a better understanding than we did a few years ago, but we still have a long way to go,” said Dr. Fox.
—Erica Tricarico
Suggested Reading
Seppi K, Weintraub D, Coelho M, et al. The Movement Disorder Society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26 Suppl 3:S42-S80.
PORTLAND, OR—Nonmotor symptoms are common in patients with Parkinson’s disease and they can substantially impact quality of life, according to an overview presented at the Fourth World Parkinson Congress.
“Nonmotor symptoms in Parkinson’s disease have become increasingly recognized, and the number of clinical trials that are now out there is also on the increase,” said Susan H. Fox, MD, PhD, Associate Professor of Neurology at the University of Toronto.
Over the course of the illness, nonmotor symptoms become increasingly prevalent and are major determinants of the progression of overall disability. Conflicting evidence can make it difficult to choose appropriate treatments for some nonmotor symptoms such as depression and psychosis. Additionally, neurologists lack validated scales that accurately measure nonmotor symptoms, which further complicates treatment. Nevertheless, the literature does provide guidance for neurologists.
Managing Depression
Depression can affect as much as 60% of patients with Parkinson’s disease, according to the Parkinson’s Disease Foundation. Most interventions for depression have not been assessed extensively in patients with Parkinson’s disease, said Dr. Fox. Tricyclic antidepressants such as amitriptyline were evaluated in Parkinson’s disease, but study populations have been small, and the evidence has been conflicting. Other interventions for depression include selective serotonin reuptake inhibitors (SSRIs) such as citalopram, sertraline, paroxetine, and fluoxetine. Evidence for these drugs is considered insufficient.
A study of nortriptyline and paroxetine versus placebo found that nortriptyline significantly reduced depression, but that paroxetine did not. A follow-up study, however, comparing paroxetine to venlafaxine showed that paroxetine was effective in patients with Parkinson’s disease and depression.
Pramipexole, a dopamine agonist, may be an effective intervention for depression in Parkinson’s disease, according to Barone et al. Additionally, rasagiline, a monoamine oxidase-B inhibitor, has been tested in patients with Parkinson’s disease. Evidence suggests that rasagiline has a nonsignificant clinical effect on depression in these patients. Richard et al concluded that venlafaxine may be effective in this population. Their study did not identify any safety concerns. According to Dobkin et al, cognitive behavioral therapy may be an effective nonpharmacologic treatment for depression in Parkinson’s disease.
Cognitive Problems
Clinical trials so far have provided insufficient evidence about the efficacy of the acetylcholinesterase inhibitors donepezil and galantamine for treating cognitive impairment such as dementia in Parkinson’s disease. Studies do suggest, however, that rivastigmine promotes positive outcomes among patients with cognitive problems, but adverse events are common. Researchers compared oral and patch preparations of rivastigmine in a long-term open-label study that included a large number of patients. Fewer patients experienced tremor with the patch, compared with the oral formulation.
The data for memantine as an intervention for cognitive impairment in Parkinson’s disease are mixed. The drug is considered to have insufficient evidence. Exercise and cognitive behavioral therapy have also been studied for cognitive impairment, but experts have not developed evidence-based recommendations about these interventions.
Measuring Psychosis
Psychosis can cause significant morbidity in patients with Parkinson’s disease. Treating psychosis can be complicated because symptoms such as hallucinations, delusions, and paranoia may not persist. It may be difficult to determine whether the intervention reduced these psychotic symptoms or whether they resolved themselves, said Dr. Fox.
In addition, a lack of widely used validated scales makes measuring psychosis in Parkinson’s disease more difficult. Trials often have used rating scales borrowed from Alzheimer’s disease research. The difference between Alzheimer’s disease and Parkinson’s disease may bias the study results or cause researchers to overlook a drug that may provide benefit, said Dr. Fox.
Still, the literature does provide guidance. Overall, clozapine is considered effective in controlling psychosis in Parkinson’s disease. The associated risk of agranulocytosis makes this treatment less popular, however. As a result, some physicians avoid prescribing clozapine because it requires patients to undergo specialized blood monitoring.
Quetiapine may help to manage psychosis in Parkinson’s disease; most physicians would consider it a first-line agent for treating psychosis because of its ease of use, said Dr. Fox. However, insufficient evidence supports the drug’s use. Pimavanserin, a 5-HT2A inverse agonist, was recently approved for treatment of psychosis in Parkinson’s disease.
Other Nonmotor Symptoms
Autonomic dysfunctions such as overactive bladder syndrome, sialorrhoea, and constipation are also common nonmotor symptoms of Parkinson’s disease. Studies show that botulinum toxins are efficacious for treating sialorrhoea in Parkinson’s disease. Side effects such as dry mouth, transient swallowing difficulties, and severe dysphagia have been reported, although the latter is rare.
Lubiprostrone is considered likely efficacious for treating constipation in Parkinson’s disease. Researchers concluded that there is insufficient evidence for the drug’s safety in patients with Parkinson’s disease, however. Typical adverse events include nausea, diarrhea, and dyspnea.
When it comes to treating sleep disorders associated with Parkinson’s disease (eg, insomnia, excessive daytime somnolence, and sudden onset of sleep), there is insufficient evidence. Drugs such as melatonin and eszopiclone are not well studied in this population.
“I don’t think we fully understand the pathology or the cause of many nonmotor symptoms. Certainly we have a better understanding than we did a few years ago, but we still have a long way to go,” said Dr. Fox.
—Erica Tricarico
Suggested Reading
Seppi K, Weintraub D, Coelho M, et al. The Movement Disorder Society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26 Suppl 3:S42-S80.
PORTLAND, OR—Nonmotor symptoms are common in patients with Parkinson’s disease and they can substantially impact quality of life, according to an overview presented at the Fourth World Parkinson Congress.
“Nonmotor symptoms in Parkinson’s disease have become increasingly recognized, and the number of clinical trials that are now out there is also on the increase,” said Susan H. Fox, MD, PhD, Associate Professor of Neurology at the University of Toronto.
Over the course of the illness, nonmotor symptoms become increasingly prevalent and are major determinants of the progression of overall disability. Conflicting evidence can make it difficult to choose appropriate treatments for some nonmotor symptoms such as depression and psychosis. Additionally, neurologists lack validated scales that accurately measure nonmotor symptoms, which further complicates treatment. Nevertheless, the literature does provide guidance for neurologists.
Managing Depression
Depression can affect as much as 60% of patients with Parkinson’s disease, according to the Parkinson’s Disease Foundation. Most interventions for depression have not been assessed extensively in patients with Parkinson’s disease, said Dr. Fox. Tricyclic antidepressants such as amitriptyline were evaluated in Parkinson’s disease, but study populations have been small, and the evidence has been conflicting. Other interventions for depression include selective serotonin reuptake inhibitors (SSRIs) such as citalopram, sertraline, paroxetine, and fluoxetine. Evidence for these drugs is considered insufficient.
A study of nortriptyline and paroxetine versus placebo found that nortriptyline significantly reduced depression, but that paroxetine did not. A follow-up study, however, comparing paroxetine to venlafaxine showed that paroxetine was effective in patients with Parkinson’s disease and depression.
Pramipexole, a dopamine agonist, may be an effective intervention for depression in Parkinson’s disease, according to Barone et al. Additionally, rasagiline, a monoamine oxidase-B inhibitor, has been tested in patients with Parkinson’s disease. Evidence suggests that rasagiline has a nonsignificant clinical effect on depression in these patients. Richard et al concluded that venlafaxine may be effective in this population. Their study did not identify any safety concerns. According to Dobkin et al, cognitive behavioral therapy may be an effective nonpharmacologic treatment for depression in Parkinson’s disease.
Cognitive Problems
Clinical trials so far have provided insufficient evidence about the efficacy of the acetylcholinesterase inhibitors donepezil and galantamine for treating cognitive impairment such as dementia in Parkinson’s disease. Studies do suggest, however, that rivastigmine promotes positive outcomes among patients with cognitive problems, but adverse events are common. Researchers compared oral and patch preparations of rivastigmine in a long-term open-label study that included a large number of patients. Fewer patients experienced tremor with the patch, compared with the oral formulation.
The data for memantine as an intervention for cognitive impairment in Parkinson’s disease are mixed. The drug is considered to have insufficient evidence. Exercise and cognitive behavioral therapy have also been studied for cognitive impairment, but experts have not developed evidence-based recommendations about these interventions.
Measuring Psychosis
Psychosis can cause significant morbidity in patients with Parkinson’s disease. Treating psychosis can be complicated because symptoms such as hallucinations, delusions, and paranoia may not persist. It may be difficult to determine whether the intervention reduced these psychotic symptoms or whether they resolved themselves, said Dr. Fox.
In addition, a lack of widely used validated scales makes measuring psychosis in Parkinson’s disease more difficult. Trials often have used rating scales borrowed from Alzheimer’s disease research. The difference between Alzheimer’s disease and Parkinson’s disease may bias the study results or cause researchers to overlook a drug that may provide benefit, said Dr. Fox.
Still, the literature does provide guidance. Overall, clozapine is considered effective in controlling psychosis in Parkinson’s disease. The associated risk of agranulocytosis makes this treatment less popular, however. As a result, some physicians avoid prescribing clozapine because it requires patients to undergo specialized blood monitoring.
Quetiapine may help to manage psychosis in Parkinson’s disease; most physicians would consider it a first-line agent for treating psychosis because of its ease of use, said Dr. Fox. However, insufficient evidence supports the drug’s use. Pimavanserin, a 5-HT2A inverse agonist, was recently approved for treatment of psychosis in Parkinson’s disease.
Other Nonmotor Symptoms
Autonomic dysfunctions such as overactive bladder syndrome, sialorrhoea, and constipation are also common nonmotor symptoms of Parkinson’s disease. Studies show that botulinum toxins are efficacious for treating sialorrhoea in Parkinson’s disease. Side effects such as dry mouth, transient swallowing difficulties, and severe dysphagia have been reported, although the latter is rare.
Lubiprostrone is considered likely efficacious for treating constipation in Parkinson’s disease. Researchers concluded that there is insufficient evidence for the drug’s safety in patients with Parkinson’s disease, however. Typical adverse events include nausea, diarrhea, and dyspnea.
When it comes to treating sleep disorders associated with Parkinson’s disease (eg, insomnia, excessive daytime somnolence, and sudden onset of sleep), there is insufficient evidence. Drugs such as melatonin and eszopiclone are not well studied in this population.
“I don’t think we fully understand the pathology or the cause of many nonmotor symptoms. Certainly we have a better understanding than we did a few years ago, but we still have a long way to go,” said Dr. Fox.
—Erica Tricarico
Suggested Reading
Seppi K, Weintraub D, Coelho M, et al. The Movement Disorder Society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26 Suppl 3:S42-S80.
Trials Will Address Unanswered Questions About Endovascular Therapy
BALTIMORE—Data from five large trials, including the MR CLEAN trial, published in the New England Journal of Medicine have greatly improved understanding of endovascular therapy for acute stroke. They have indicated that the therapy is effective if initiated within six hours of onset and suggested that baseline collateral flow predicts successful reperfusion and response to therapy. Research currently under way could address several questions that remain unanswered, according to an overview presented at the 141st Annual Meeting of the American Neurological Association.
Defining the Treatment Window
The most important of these questions is whether thrombectomy is effective in appropriately selected patients if administered at more than six hours from onset, said Joseph P. Broderick, MD, Professor of Neurology and Rehabilitation Medicine at the University of Cincinnati College of Medicine. “We are going away from chronological measures of infarction to physiological measures of brain ischemia. That is how we are going to try to appropriately select patients.”
The DEFUSE 3 trial is based on the premise that after six hours from onset, many patients with stroke still have salvageable tissue. The investigators are examining whether imaging can identify these patients and whether devices cleared by the FDA can benefit them. Eligible patients have an occlusion of the internal carotid artery or an M1 occlusion and a target mismatch profile. The inclusion criteria are similar to those of other endovascular trials, except that baseline NIH Stroke Scale (NIHSS) score must be 6 or higher. Patients with a contraindication to MRI or CT perfusion are excluded from the trial, as are patients with an Alberta Stroke Program Early CT Score (ASPECTS) of less than 6 on a noncontrast CT.
Patients are randomized to thrombectomy plus standard medical therapy or standard medical therapy alone. Treatment is delivered within 16 hours of stroke onset using any device that has been cleared for thrombectomy by the FDA (eg, the Solitaire device or the Penumbra aspiration system). Intra-arterial t-PA is not allowed in the trial, and the investigators strongly recommend conscious sedation rather than general anesthesia. The trial’s adaptive design will identify, at interim analyses, the group with the best prospect for showing benefit from endovascular treatment, based on baseline core lesion volumes and the times since stroke onset. The investigators plan to enroll a maximum sample size of 476 and to perform interim analyses when enrollment reaches 200 patients and 340 patients.
The DAWN trial will test endovascular therapy when administered at six to 24 hours after onset. Its primary objective is to evaluate the hypothesis that Trevo thrombectomy plus medical management provides superior clinical outcome at 90 days, compared with medical management alone, in appropriately selected patients. The primary end point is modified Rankin scale (mRS) score at 90 days. Participants will be randomized in a 1:1 ratio at as many as 50 sites. Unlike in DEFUSE 3, the DAWN investigators will be examining patients with a clinical–imaging mismatch. “It will end up having a different but overlapping population of patients, as compared to DEFUSE 3,” said Dr. Broderick. “My prediction is that patients, no matter which arm they are randomized to, will have better outcomes in this particular trial because their core volumes will be smaller than in DEFUSE III.”
In addition, the POSITIVE trial will examine whether patients with acute ischemic stroke who are refractory to or ineligible for t-PA have less stroke-related disability and better functional outcomes if they receive thrombectomy, compared with best medical therapy, at six to 12 hours after onset. Patients without an associated large penumbra, as defined by physiologic imaging, will be excluded from the trial. Disability will be assessed by mRS.
Finally, the MR CLEAN LATE trial will compare endovascular therapy and best medical therapy with endovascular therapy alone in patients with acute stroke and moderate to good collateral flow. Treatment will be administered at six to 12 hours after stroke onset. The trial has not begun, but will enroll 500 patients, including some with wake-up stoke. The investigators will examine whether the two groups’ outcomes differ by 10%.
Triaging Patients With Suspected Large Artery Occlusions
Another unanswered question is how emergency physicians can best triage patients with acute stroke who are most likely to have large artery occlusions. Mobile stroke units, for example, can identify large right occlusion on a baseline thin-slice CT or on CT angiography. Or emergency medical responders can use brief prehospital scales (eg, the Cincinnati Stroke Triage Assessment Tool), which take less time to administer than CT. Identifying the best method of triage could greatly reduce time to reperfusion, said Dr. Broderick.
The RACECAT trial, which has not yet been initiated, may provide evidence to address this question. Emergency responders in Catalonia, Spain, will use the Rapid Arterial Occlusion Evaluation (RACE) scale, which has more items than some of the other triage scales, to identify patients with acute stroke and suspected large vessel occlusion. After the responders contact the stroke neurologists on call using a telestroke system, eligible participants will be randomized according to a predetermined sequence to either transfer to the closest local stroke center or direct transfer to an endovascular stroke center. The study allocations will allow for three additional comparisons: between two groups of 12 hours, between metropolitan and provincial areas, and between workdays and weekends. The primary end point is the mRS at 90 days.
Identifying the Best Level of Anesthesia
Other trials will seek to determine whether general anesthesia or planned conscious sedation is more cost-effective in patients who are eligible for either procedure. Researchers previously examined this question in the IMS III trial. Setting aside patients who underwent medically indicated general anesthesia (who had large strokes and many comorbidities and tended to have poor outcomes), the researchers found a trend toward better outcomes among patients who underwent conscious sedation, compared with patients who received general anesthesia. In addition, general anesthesia cost approximately $16,000 more than conscious sedation did.
In the prospective SIESTA trial, patients with acute ischemic stroke were randomized in a 1:1 ratio to a nonintubated state or to an intubated state for endovascular stroke treatment. The primary outcome measure was NIHSS at 24 hours after the intervention. Secondary outcome measures included mRS at three months and inpatient mortality. Conscious sedation was not associated with any advantage over general anesthesia in this small randomized trial, according to the researchers.
In addition, investigators are recruiting patients for the GOLIATH trial, in which patients will be randomized to general anesthesia or local anesthesia. The primary outcome measure will be growth of the ischemic lesion on diffusion-weighted imaging (DWI). Secondary outcome measures will include time from arrival to groin puncture and recanalization, blood pressure during intervention, and mRS.
Thrombectomy With or Without Thrombolysis
Another unanswered question is whether thrombectomy alone provides greater benefit than IV t-PA followed by thrombectomy for patients with acute ischemic stroke. Investigators in the Netherlands are conducting the MR CLEAN NO IV trial to answer this question. They plan to include 500 patients who are taken directly to a comprehensive stroke center. One group will receive IV t-PA plus endovascular treatment, and the other group will receive endovascular treatment alone.
—Erik Greb
Suggested Reading
Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-1731.
Lansberg MG, Cereda CW, Mlynash M, et al. Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology. 2015;85(8):708-714.
Schönenberger S, Uhlmann L, Hacke W, et al. Effect of conscious sedation vs general anesthesia on early neurological improvement among patients with ischemic stroke undergoing endovascular thrombectomy: a randomized clinical trial. JAMA. 2016;316(19):1986-1996.
BALTIMORE—Data from five large trials, including the MR CLEAN trial, published in the New England Journal of Medicine have greatly improved understanding of endovascular therapy for acute stroke. They have indicated that the therapy is effective if initiated within six hours of onset and suggested that baseline collateral flow predicts successful reperfusion and response to therapy. Research currently under way could address several questions that remain unanswered, according to an overview presented at the 141st Annual Meeting of the American Neurological Association.
Defining the Treatment Window
The most important of these questions is whether thrombectomy is effective in appropriately selected patients if administered at more than six hours from onset, said Joseph P. Broderick, MD, Professor of Neurology and Rehabilitation Medicine at the University of Cincinnati College of Medicine. “We are going away from chronological measures of infarction to physiological measures of brain ischemia. That is how we are going to try to appropriately select patients.”
The DEFUSE 3 trial is based on the premise that after six hours from onset, many patients with stroke still have salvageable tissue. The investigators are examining whether imaging can identify these patients and whether devices cleared by the FDA can benefit them. Eligible patients have an occlusion of the internal carotid artery or an M1 occlusion and a target mismatch profile. The inclusion criteria are similar to those of other endovascular trials, except that baseline NIH Stroke Scale (NIHSS) score must be 6 or higher. Patients with a contraindication to MRI or CT perfusion are excluded from the trial, as are patients with an Alberta Stroke Program Early CT Score (ASPECTS) of less than 6 on a noncontrast CT.
Patients are randomized to thrombectomy plus standard medical therapy or standard medical therapy alone. Treatment is delivered within 16 hours of stroke onset using any device that has been cleared for thrombectomy by the FDA (eg, the Solitaire device or the Penumbra aspiration system). Intra-arterial t-PA is not allowed in the trial, and the investigators strongly recommend conscious sedation rather than general anesthesia. The trial’s adaptive design will identify, at interim analyses, the group with the best prospect for showing benefit from endovascular treatment, based on baseline core lesion volumes and the times since stroke onset. The investigators plan to enroll a maximum sample size of 476 and to perform interim analyses when enrollment reaches 200 patients and 340 patients.
The DAWN trial will test endovascular therapy when administered at six to 24 hours after onset. Its primary objective is to evaluate the hypothesis that Trevo thrombectomy plus medical management provides superior clinical outcome at 90 days, compared with medical management alone, in appropriately selected patients. The primary end point is modified Rankin scale (mRS) score at 90 days. Participants will be randomized in a 1:1 ratio at as many as 50 sites. Unlike in DEFUSE 3, the DAWN investigators will be examining patients with a clinical–imaging mismatch. “It will end up having a different but overlapping population of patients, as compared to DEFUSE 3,” said Dr. Broderick. “My prediction is that patients, no matter which arm they are randomized to, will have better outcomes in this particular trial because their core volumes will be smaller than in DEFUSE III.”
In addition, the POSITIVE trial will examine whether patients with acute ischemic stroke who are refractory to or ineligible for t-PA have less stroke-related disability and better functional outcomes if they receive thrombectomy, compared with best medical therapy, at six to 12 hours after onset. Patients without an associated large penumbra, as defined by physiologic imaging, will be excluded from the trial. Disability will be assessed by mRS.
Finally, the MR CLEAN LATE trial will compare endovascular therapy and best medical therapy with endovascular therapy alone in patients with acute stroke and moderate to good collateral flow. Treatment will be administered at six to 12 hours after stroke onset. The trial has not begun, but will enroll 500 patients, including some with wake-up stoke. The investigators will examine whether the two groups’ outcomes differ by 10%.
Triaging Patients With Suspected Large Artery Occlusions
Another unanswered question is how emergency physicians can best triage patients with acute stroke who are most likely to have large artery occlusions. Mobile stroke units, for example, can identify large right occlusion on a baseline thin-slice CT or on CT angiography. Or emergency medical responders can use brief prehospital scales (eg, the Cincinnati Stroke Triage Assessment Tool), which take less time to administer than CT. Identifying the best method of triage could greatly reduce time to reperfusion, said Dr. Broderick.
The RACECAT trial, which has not yet been initiated, may provide evidence to address this question. Emergency responders in Catalonia, Spain, will use the Rapid Arterial Occlusion Evaluation (RACE) scale, which has more items than some of the other triage scales, to identify patients with acute stroke and suspected large vessel occlusion. After the responders contact the stroke neurologists on call using a telestroke system, eligible participants will be randomized according to a predetermined sequence to either transfer to the closest local stroke center or direct transfer to an endovascular stroke center. The study allocations will allow for three additional comparisons: between two groups of 12 hours, between metropolitan and provincial areas, and between workdays and weekends. The primary end point is the mRS at 90 days.
Identifying the Best Level of Anesthesia
Other trials will seek to determine whether general anesthesia or planned conscious sedation is more cost-effective in patients who are eligible for either procedure. Researchers previously examined this question in the IMS III trial. Setting aside patients who underwent medically indicated general anesthesia (who had large strokes and many comorbidities and tended to have poor outcomes), the researchers found a trend toward better outcomes among patients who underwent conscious sedation, compared with patients who received general anesthesia. In addition, general anesthesia cost approximately $16,000 more than conscious sedation did.
In the prospective SIESTA trial, patients with acute ischemic stroke were randomized in a 1:1 ratio to a nonintubated state or to an intubated state for endovascular stroke treatment. The primary outcome measure was NIHSS at 24 hours after the intervention. Secondary outcome measures included mRS at three months and inpatient mortality. Conscious sedation was not associated with any advantage over general anesthesia in this small randomized trial, according to the researchers.
In addition, investigators are recruiting patients for the GOLIATH trial, in which patients will be randomized to general anesthesia or local anesthesia. The primary outcome measure will be growth of the ischemic lesion on diffusion-weighted imaging (DWI). Secondary outcome measures will include time from arrival to groin puncture and recanalization, blood pressure during intervention, and mRS.
Thrombectomy With or Without Thrombolysis
Another unanswered question is whether thrombectomy alone provides greater benefit than IV t-PA followed by thrombectomy for patients with acute ischemic stroke. Investigators in the Netherlands are conducting the MR CLEAN NO IV trial to answer this question. They plan to include 500 patients who are taken directly to a comprehensive stroke center. One group will receive IV t-PA plus endovascular treatment, and the other group will receive endovascular treatment alone.
—Erik Greb
Suggested Reading
Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-1731.
Lansberg MG, Cereda CW, Mlynash M, et al. Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology. 2015;85(8):708-714.
Schönenberger S, Uhlmann L, Hacke W, et al. Effect of conscious sedation vs general anesthesia on early neurological improvement among patients with ischemic stroke undergoing endovascular thrombectomy: a randomized clinical trial. JAMA. 2016;316(19):1986-1996.
BALTIMORE—Data from five large trials, including the MR CLEAN trial, published in the New England Journal of Medicine have greatly improved understanding of endovascular therapy for acute stroke. They have indicated that the therapy is effective if initiated within six hours of onset and suggested that baseline collateral flow predicts successful reperfusion and response to therapy. Research currently under way could address several questions that remain unanswered, according to an overview presented at the 141st Annual Meeting of the American Neurological Association.
Defining the Treatment Window
The most important of these questions is whether thrombectomy is effective in appropriately selected patients if administered at more than six hours from onset, said Joseph P. Broderick, MD, Professor of Neurology and Rehabilitation Medicine at the University of Cincinnati College of Medicine. “We are going away from chronological measures of infarction to physiological measures of brain ischemia. That is how we are going to try to appropriately select patients.”
The DEFUSE 3 trial is based on the premise that after six hours from onset, many patients with stroke still have salvageable tissue. The investigators are examining whether imaging can identify these patients and whether devices cleared by the FDA can benefit them. Eligible patients have an occlusion of the internal carotid artery or an M1 occlusion and a target mismatch profile. The inclusion criteria are similar to those of other endovascular trials, except that baseline NIH Stroke Scale (NIHSS) score must be 6 or higher. Patients with a contraindication to MRI or CT perfusion are excluded from the trial, as are patients with an Alberta Stroke Program Early CT Score (ASPECTS) of less than 6 on a noncontrast CT.
Patients are randomized to thrombectomy plus standard medical therapy or standard medical therapy alone. Treatment is delivered within 16 hours of stroke onset using any device that has been cleared for thrombectomy by the FDA (eg, the Solitaire device or the Penumbra aspiration system). Intra-arterial t-PA is not allowed in the trial, and the investigators strongly recommend conscious sedation rather than general anesthesia. The trial’s adaptive design will identify, at interim analyses, the group with the best prospect for showing benefit from endovascular treatment, based on baseline core lesion volumes and the times since stroke onset. The investigators plan to enroll a maximum sample size of 476 and to perform interim analyses when enrollment reaches 200 patients and 340 patients.
The DAWN trial will test endovascular therapy when administered at six to 24 hours after onset. Its primary objective is to evaluate the hypothesis that Trevo thrombectomy plus medical management provides superior clinical outcome at 90 days, compared with medical management alone, in appropriately selected patients. The primary end point is modified Rankin scale (mRS) score at 90 days. Participants will be randomized in a 1:1 ratio at as many as 50 sites. Unlike in DEFUSE 3, the DAWN investigators will be examining patients with a clinical–imaging mismatch. “It will end up having a different but overlapping population of patients, as compared to DEFUSE 3,” said Dr. Broderick. “My prediction is that patients, no matter which arm they are randomized to, will have better outcomes in this particular trial because their core volumes will be smaller than in DEFUSE III.”
In addition, the POSITIVE trial will examine whether patients with acute ischemic stroke who are refractory to or ineligible for t-PA have less stroke-related disability and better functional outcomes if they receive thrombectomy, compared with best medical therapy, at six to 12 hours after onset. Patients without an associated large penumbra, as defined by physiologic imaging, will be excluded from the trial. Disability will be assessed by mRS.
Finally, the MR CLEAN LATE trial will compare endovascular therapy and best medical therapy with endovascular therapy alone in patients with acute stroke and moderate to good collateral flow. Treatment will be administered at six to 12 hours after stroke onset. The trial has not begun, but will enroll 500 patients, including some with wake-up stoke. The investigators will examine whether the two groups’ outcomes differ by 10%.
Triaging Patients With Suspected Large Artery Occlusions
Another unanswered question is how emergency physicians can best triage patients with acute stroke who are most likely to have large artery occlusions. Mobile stroke units, for example, can identify large right occlusion on a baseline thin-slice CT or on CT angiography. Or emergency medical responders can use brief prehospital scales (eg, the Cincinnati Stroke Triage Assessment Tool), which take less time to administer than CT. Identifying the best method of triage could greatly reduce time to reperfusion, said Dr. Broderick.
The RACECAT trial, which has not yet been initiated, may provide evidence to address this question. Emergency responders in Catalonia, Spain, will use the Rapid Arterial Occlusion Evaluation (RACE) scale, which has more items than some of the other triage scales, to identify patients with acute stroke and suspected large vessel occlusion. After the responders contact the stroke neurologists on call using a telestroke system, eligible participants will be randomized according to a predetermined sequence to either transfer to the closest local stroke center or direct transfer to an endovascular stroke center. The study allocations will allow for three additional comparisons: between two groups of 12 hours, between metropolitan and provincial areas, and between workdays and weekends. The primary end point is the mRS at 90 days.
Identifying the Best Level of Anesthesia
Other trials will seek to determine whether general anesthesia or planned conscious sedation is more cost-effective in patients who are eligible for either procedure. Researchers previously examined this question in the IMS III trial. Setting aside patients who underwent medically indicated general anesthesia (who had large strokes and many comorbidities and tended to have poor outcomes), the researchers found a trend toward better outcomes among patients who underwent conscious sedation, compared with patients who received general anesthesia. In addition, general anesthesia cost approximately $16,000 more than conscious sedation did.
In the prospective SIESTA trial, patients with acute ischemic stroke were randomized in a 1:1 ratio to a nonintubated state or to an intubated state for endovascular stroke treatment. The primary outcome measure was NIHSS at 24 hours after the intervention. Secondary outcome measures included mRS at three months and inpatient mortality. Conscious sedation was not associated with any advantage over general anesthesia in this small randomized trial, according to the researchers.
In addition, investigators are recruiting patients for the GOLIATH trial, in which patients will be randomized to general anesthesia or local anesthesia. The primary outcome measure will be growth of the ischemic lesion on diffusion-weighted imaging (DWI). Secondary outcome measures will include time from arrival to groin puncture and recanalization, blood pressure during intervention, and mRS.
Thrombectomy With or Without Thrombolysis
Another unanswered question is whether thrombectomy alone provides greater benefit than IV t-PA followed by thrombectomy for patients with acute ischemic stroke. Investigators in the Netherlands are conducting the MR CLEAN NO IV trial to answer this question. They plan to include 500 patients who are taken directly to a comprehensive stroke center. One group will receive IV t-PA plus endovascular treatment, and the other group will receive endovascular treatment alone.
—Erik Greb
Suggested Reading
Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-1731.
Lansberg MG, Cereda CW, Mlynash M, et al. Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology. 2015;85(8):708-714.
Schönenberger S, Uhlmann L, Hacke W, et al. Effect of conscious sedation vs general anesthesia on early neurological improvement among patients with ischemic stroke undergoing endovascular thrombectomy: a randomized clinical trial. JAMA. 2016;316(19):1986-1996.