Vascular

LOS ANGELES – The equipoise between carotid stenting and endarterectomy received a further boost in 10-year results from the landmark Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) that compared the two options head-to-head.

Reported the day after results from another big trial that pitted carotid stenting against surgery, the Asymptomatic Carotid Trial (ACT I), the new long-term results from the CREST study mean that deciding among the options relies largely on patient preference although individual clinical characteristics might favor one approach or the other, experts said.

Mitchel L. Zoler/Frontline Medical News

The big remaining unknown and wild card is whether doing no procedural intervention at all and relying entirely on optimal, contemporary medical treatment works just as well as endarterectomy or carotid stenting. The role for stand-alone medical therapy against carotid surgery or stenting (on top of medical therapy) is currently undergoing a formal, direct comparison in the randomized Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2).

Taking the 5-year outcome results from ACT I and the 10-year outcome results from CREST both into account, “we now have a lot of evidence that both carotid stenting and surgery are safe and durable. The results support both options” for either patients with symptomatic carotid artery stenosis or asymptomatic patients with carotid stenosis as extensive as in the patients enrolled in these trials, said Dr. Thomas G. Brott at the International Stroke Conference.

“In routine practice, we lay out the options of endarterectomy, carotid stenting, or no intervention with just medical treatment to patients and let them decide,” noted Dr. Brott, professor of neurology and director of research at the Mayo Clinic in Jacksonville, Fla.

CREST randomized 2,502 symptomatic or asymptomatic patients with significant carotid stenosis during 2000-2008 at 117 U.S. and Canadian centers. From this group, 1,607 consented and were available for long-term follow-up, done at a median of 7.4 years and as long as 10 years after follow-up.

The study’s primary, long-term endpoint was stroke, MI, or death during the periprocedural period (30 days after treatment or 36 days after enrollment depending on when the procedural intervention occurred) plus the rate of ipsilateral stroke during up to 10 years of follow-up. This combined endpoint occurred in 10% of the patients who underwent endarterectomy and in 12% of those who had stenting, a difference that was not statistically significant, Dr. Brott reported. Concurrent with his presentation at the meeting, sponsored by the American Heart Association, the results also were published online (N Engl J Med. 2016 Feb 18. doi: 10.1056/NEJMoa1505215).

The results included a secondary endpoint that showed a significant benefit for endarterectomy. The tally of periprocedural strokes or deaths plus ipsilateral strokes during 10-year follow-up was 8% for the surgical group and 11% for those who received a stent, a 37% excess hazard with stenting.

Dr. Brott attributed this secondary difference between the two arms of the study to a statistically significant excess of stroke or death during the periprocedural period in the patients treated by stenting, and more specifically an excess of strokes. The rate of total periprocedural strokes was 4% with stenting and 2% with endarterectomy, a statistically significant difference. Although an embolic protection device was used “when feasible” during stenting, this protection can be fallible, Dr. Brott noted. In contrast, the results from the ACT I trial showed no statistically significant difference in the rate of periprocedural total strokes between the stented and endarterectomy patients.

Dr. Brott had no relevant disclosures. The CREST trial received partial funding from Abbott Vascular.

[email protected]

On Twitter @mitchelzoler

LOS ANGELES – The equipoise between carotid stenting and endarterectomy received a further boost in 10-year results from the landmark Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) that compared the two options head-to-head.

Reported the day after results from another big trial that pitted carotid stenting against surgery, the Asymptomatic Carotid Trial (ACT I), the new long-term results from the CREST study mean that deciding among the options relies largely on patient preference although individual clinical characteristics might favor one approach or the other, experts said.

Mitchel L. Zoler/Frontline Medical News

The big remaining unknown and wild card is whether doing no procedural intervention at all and relying entirely on optimal, contemporary medical treatment works just as well as endarterectomy or carotid stenting. The role for stand-alone medical therapy against carotid surgery or stenting (on top of medical therapy) is currently undergoing a formal, direct comparison in the randomized Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2).

Taking the 5-year outcome results from ACT I and the 10-year outcome results from CREST both into account, “we now have a lot of evidence that both carotid stenting and surgery are safe and durable. The results support both options” for either patients with symptomatic carotid artery stenosis or asymptomatic patients with carotid stenosis as extensive as in the patients enrolled in these trials, said Dr. Thomas G. Brott at the International Stroke Conference.

“In routine practice, we lay out the options of endarterectomy, carotid stenting, or no intervention with just medical treatment to patients and let them decide,” noted Dr. Brott, professor of neurology and director of research at the Mayo Clinic in Jacksonville, Fla.

CREST randomized 2,502 symptomatic or asymptomatic patients with significant carotid stenosis during 2000-2008 at 117 U.S. and Canadian centers. From this group, 1,607 consented and were available for long-term follow-up, done at a median of 7.4 years and as long as 10 years after follow-up.

The study’s primary, long-term endpoint was stroke, MI, or death during the periprocedural period (30 days after treatment or 36 days after enrollment depending on when the procedural intervention occurred) plus the rate of ipsilateral stroke during up to 10 years of follow-up. This combined endpoint occurred in 10% of the patients who underwent endarterectomy and in 12% of those who had stenting, a difference that was not statistically significant, Dr. Brott reported. Concurrent with his presentation at the meeting, sponsored by the American Heart Association, the results also were published online (N Engl J Med. 2016 Feb 18. doi: 10.1056/NEJMoa1505215).

The results included a secondary endpoint that showed a significant benefit for endarterectomy. The tally of periprocedural strokes or deaths plus ipsilateral strokes during 10-year follow-up was 8% for the surgical group and 11% for those who received a stent, a 37% excess hazard with stenting.

Dr. Brott attributed this secondary difference between the two arms of the study to a statistically significant excess of stroke or death during the periprocedural period in the patients treated by stenting, and more specifically an excess of strokes. The rate of total periprocedural strokes was 4% with stenting and 2% with endarterectomy, a statistically significant difference. Although an embolic protection device was used “when feasible” during stenting, this protection can be fallible, Dr. Brott noted. In contrast, the results from the ACT I trial showed no statistically significant difference in the rate of periprocedural total strokes between the stented and endarterectomy patients.

Dr. Brott had no relevant disclosures. The CREST trial received partial funding from Abbott Vascular.

[email protected]

On Twitter @mitchelzoler

LOS ANGELES – The equipoise between carotid stenting and endarterectomy received a further boost in 10-year results from the landmark Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) that compared the two options head-to-head.

Reported the day after results from another big trial that pitted carotid stenting against surgery, the Asymptomatic Carotid Trial (ACT I), the new long-term results from the CREST study mean that deciding among the options relies largely on patient preference although individual clinical characteristics might favor one approach or the other, experts said.

Mitchel L. Zoler/Frontline Medical News

The big remaining unknown and wild card is whether doing no procedural intervention at all and relying entirely on optimal, contemporary medical treatment works just as well as endarterectomy or carotid stenting. The role for stand-alone medical therapy against carotid surgery or stenting (on top of medical therapy) is currently undergoing a formal, direct comparison in the randomized Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2).

Taking the 5-year outcome results from ACT I and the 10-year outcome results from CREST both into account, “we now have a lot of evidence that both carotid stenting and surgery are safe and durable. The results support both options” for either patients with symptomatic carotid artery stenosis or asymptomatic patients with carotid stenosis as extensive as in the patients enrolled in these trials, said Dr. Thomas G. Brott at the International Stroke Conference.

“In routine practice, we lay out the options of endarterectomy, carotid stenting, or no intervention with just medical treatment to patients and let them decide,” noted Dr. Brott, professor of neurology and director of research at the Mayo Clinic in Jacksonville, Fla.

CREST randomized 2,502 symptomatic or asymptomatic patients with significant carotid stenosis during 2000-2008 at 117 U.S. and Canadian centers. From this group, 1,607 consented and were available for long-term follow-up, done at a median of 7.4 years and as long as 10 years after follow-up.

The study’s primary, long-term endpoint was stroke, MI, or death during the periprocedural period (30 days after treatment or 36 days after enrollment depending on when the procedural intervention occurred) plus the rate of ipsilateral stroke during up to 10 years of follow-up. This combined endpoint occurred in 10% of the patients who underwent endarterectomy and in 12% of those who had stenting, a difference that was not statistically significant, Dr. Brott reported. Concurrent with his presentation at the meeting, sponsored by the American Heart Association, the results also were published online (N Engl J Med. 2016 Feb 18. doi: 10.1056/NEJMoa1505215).

The results included a secondary endpoint that showed a significant benefit for endarterectomy. The tally of periprocedural strokes or deaths plus ipsilateral strokes during 10-year follow-up was 8% for the surgical group and 11% for those who received a stent, a 37% excess hazard with stenting.

Dr. Brott attributed this secondary difference between the two arms of the study to a statistically significant excess of stroke or death during the periprocedural period in the patients treated by stenting, and more specifically an excess of strokes. The rate of total periprocedural strokes was 4% with stenting and 2% with endarterectomy, a statistically significant difference. Although an embolic protection device was used “when feasible” during stenting, this protection can be fallible, Dr. Brott noted. In contrast, the results from the ACT I trial showed no statistically significant difference in the rate of periprocedural total strokes between the stented and endarterectomy patients.

Dr. Brott had no relevant disclosures. The CREST trial received partial funding from Abbott Vascular.

[email protected]

On Twitter @mitchelzoler

LOS ANGELES – In asymptomatic patients under 80 years old, carotid stenting and endarterectomy perform equally as well for severe carotid stenosis out to 5 years, according to a randomized trial published online in the New England Journal of Medicine.

Overall, 1,032 patients were stented, and 343 had endarterectomies in the trial, called Asymptomatic Carotid Trial I (ACT I). If stenting didn’t look safe on postrandomization angiography, patients were given the option of medical management or crossover into the surgical group. The subjects all had bifurcation carotid stenosis blocking at least 70% of the lumen. None were at high risk for surgical complications. “Asymptomatic” meant they hadn’t had a stroke, transient ischemic attack, or amaurosis fugax in the 6 months before enrollment. Stenting and endarterectomy were done by physicians and centers well experienced in the techniques (N Engl J Med. 2016 Feb 17. doi: 10.1056/NEJMoa1515706).

At 1 year, stenting was noninferior to endarterectomy for the primary composite endpoint of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year; the event rate was 3.8% among stent patients and 3.4% among endarterectomy patients (P = .01 for noninferiority, with a noninferiority margin of 3 percentage points).

The cumulative 5-year stroke-free survival rate was 93.1% in the stenting group and 94.7% in the endarterectomy group (P = .44).

For now, the results mean that sometimes choosing between carotid endarterectomy or stenting (or medical management) has as much to do with patient and physician preference as medical science, raising the difficult question of how to choose. In a video interview at the International Stroke Conference, investigator Dr. Lawrence Wechsler, professor of neurology/neurosurgery and chair of the department of neurology at the University of Pittsburgh, shared his thoughts on that and the other implications of the study. The work was funded by Abbott Vascular.

[email protected]

LOS ANGELES – In asymptomatic patients under 80 years old, carotid stenting and endarterectomy perform equally as well for severe carotid stenosis out to 5 years, according to a randomized trial published online in the New England Journal of Medicine.

Overall, 1,032 patients were stented, and 343 had endarterectomies in the trial, called Asymptomatic Carotid Trial I (ACT I). If stenting didn’t look safe on postrandomization angiography, patients were given the option of medical management or crossover into the surgical group. The subjects all had bifurcation carotid stenosis blocking at least 70% of the lumen. None were at high risk for surgical complications. “Asymptomatic” meant they hadn’t had a stroke, transient ischemic attack, or amaurosis fugax in the 6 months before enrollment. Stenting and endarterectomy were done by physicians and centers well experienced in the techniques (N Engl J Med. 2016 Feb 17. doi: 10.1056/NEJMoa1515706).

At 1 year, stenting was noninferior to endarterectomy for the primary composite endpoint of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year; the event rate was 3.8% among stent patients and 3.4% among endarterectomy patients (P = .01 for noninferiority, with a noninferiority margin of 3 percentage points).

The cumulative 5-year stroke-free survival rate was 93.1% in the stenting group and 94.7% in the endarterectomy group (P = .44).

For now, the results mean that sometimes choosing between carotid endarterectomy or stenting (or medical management) has as much to do with patient and physician preference as medical science, raising the difficult question of how to choose. In a video interview at the International Stroke Conference, investigator Dr. Lawrence Wechsler, professor of neurology/neurosurgery and chair of the department of neurology at the University of Pittsburgh, shared his thoughts on that and the other implications of the study. The work was funded by Abbott Vascular.

[email protected]

LOS ANGELES – In asymptomatic patients under 80 years old, carotid stenting and endarterectomy perform equally as well for severe carotid stenosis out to 5 years, according to a randomized trial published online in the New England Journal of Medicine.

Overall, 1,032 patients were stented, and 343 had endarterectomies in the trial, called Asymptomatic Carotid Trial I (ACT I). If stenting didn’t look safe on postrandomization angiography, patients were given the option of medical management or crossover into the surgical group. The subjects all had bifurcation carotid stenosis blocking at least 70% of the lumen. None were at high risk for surgical complications. “Asymptomatic” meant they hadn’t had a stroke, transient ischemic attack, or amaurosis fugax in the 6 months before enrollment. Stenting and endarterectomy were done by physicians and centers well experienced in the techniques (N Engl J Med. 2016 Feb 17. doi: 10.1056/NEJMoa1515706).

At 1 year, stenting was noninferior to endarterectomy for the primary composite endpoint of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year; the event rate was 3.8% among stent patients and 3.4% among endarterectomy patients (P = .01 for noninferiority, with a noninferiority margin of 3 percentage points).

The cumulative 5-year stroke-free survival rate was 93.1% in the stenting group and 94.7% in the endarterectomy group (P = .44).

For now, the results mean that sometimes choosing between carotid endarterectomy or stenting (or medical management) has as much to do with patient and physician preference as medical science, raising the difficult question of how to choose. In a video interview at the International Stroke Conference, investigator Dr. Lawrence Wechsler, professor of neurology/neurosurgery and chair of the department of neurology at the University of Pittsburgh, shared his thoughts on that and the other implications of the study. The work was funded by Abbott Vascular.

[email protected]

LOS ANGELES – Clot removal to recanalize the occluded intracerebral arteries of acute ischemic stroke patients was as effective for producing good outcomes in patients aged 80 years or older as it was in younger patients, according to results from a pooled analysis of 1,287 patients in five separate but similar randomized trials.

This unprecedented evidence for the safety and efficacy of thrombectomy (also known as embolectomy) in octogenarians experiencing an acute occlusive, large-vessel, proximal anterior-circulation stroke was one of several new findings from the pooled analysis that should help further push thrombectomy to the forefront of acute care for patients undergoing this type of ischemic stroke, predicted Dr. Wade S. Smith in a video interview at the International Stroke Conference.

“By looking at all the data, we have much more refined information on the robustness of the treatment across age groups, which is quite important, especially patients in the 80-plus age group,” commented Dr. Smith, professor of neurology and chief of the neurovascular division at the University of California, San Francisco.

Until now, during the year following the reports in early 2015 from all five studies, “age had been a limiting factor” in applying the practicing-changing intervention of thrombectomy to patients, he noted.

“This [the new pooled analysis] will change that,” Dr. Smith predicted. “It does not apply to patients who were infirm prior to their stroke – but for patients who were otherwise healthy, with a modified Rankin scale level of 0 or 1 at initial presentation, it appears that they benefit [from thrombectomy] regardless of their age.” In the pooled analysis, 198 of the 1,287 total patients (15%) were at least 80 years old.

“It removes age discrimination. A healthy 80-year-old may do extremely well with this treatment,” Dr. Smith said.

The consistency of benefit across a wide range of stroke severity that showed up in the trials as four distinct strata of NIH Stroke Scale scores prior to treatment was another important finding that could not previously be definitively made by analyzing each of the five trials individually.

In patients with stroke-severity scores that ranged from 10 or less (the least severely affected) to patients with scores of 21 or greater, all had post-thrombectomy improvements that clustered around the overall average number-needed-to-treat of 2.6 patients to reduce the disability of one patient at follow-up by at least one level on the modified Rankin scale.

Other notable findings from the pooled analysis were that thrombectomy also produced a consistent benefit to patients across every other subgroup examined, including sex, specific occlusion site, whether or not patients also received thrombolytic treatment with tissue plasminogen activator, and time to thrombectomy treatment (5 or fewer hours from stroke onset or more than 5 hours), reported Dr. Michael D. Hill and Dr. Tudor G. Jovin in a joint presentation at the meeting, sponsored by the American Heart Association.

Their pooled analysis, known as HERMES, pooled data from the MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA trials, all run during 2010-2014.

“Endovascular treatment is a highly effective treatment across all subgroups,” concluded Dr. Hill and Dr. Jovin as they completed their talk. “These data may provide additional support for endovascular treatment in subgroups not addressed in the individual trials.”

Concurrent with their report at the meeting, the results appeared in a paper published online (Lancet. 2016 Feb 18;doi: 10.1016/S0140-6736(16)00163-X).

Both Dr. Jovin and Dr. Hill shared the enthusiasm of Dr. Smith and others in the packed meeting room about the age finding.

“Older patients seemed to benefit even more” from thrombectomy, compared with younger patients, noted Dr. Jovin, chief of the stroke division at the University of Pittsburgh and a coinvestigator on SWIFT PRIME. “There is no reason to deny this treatment to appropriately selected patients based on age,” he said.

“There is no upper age limit,” agreed Dr. Hill, professor of neurology and director of the stroke unit at the University of Calgary (Alta.) and a coinvestigator on the ESCAPE trial. “If it’s an otherwise healthy 90-year-old who is living independently, you can surely consider them for this treatment.”

HERMES received fundings through an unrestricted grant from Medtronic. Dr. Hill and Dr. Jovin had no personal disclosures. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker.

[email protected]

On Twitter @mitchelzoler

LOS ANGELES – Clot removal to recanalize the occluded intracerebral arteries of acute ischemic stroke patients was as effective for producing good outcomes in patients aged 80 years or older as it was in younger patients, according to results from a pooled analysis of 1,287 patients in five separate but similar randomized trials.

This unprecedented evidence for the safety and efficacy of thrombectomy (also known as embolectomy) in octogenarians experiencing an acute occlusive, large-vessel, proximal anterior-circulation stroke was one of several new findings from the pooled analysis that should help further push thrombectomy to the forefront of acute care for patients undergoing this type of ischemic stroke, predicted Dr. Wade S. Smith in a video interview at the International Stroke Conference.

“By looking at all the data, we have much more refined information on the robustness of the treatment across age groups, which is quite important, especially patients in the 80-plus age group,” commented Dr. Smith, professor of neurology and chief of the neurovascular division at the University of California, San Francisco.

Until now, during the year following the reports in early 2015 from all five studies, “age had been a limiting factor” in applying the practicing-changing intervention of thrombectomy to patients, he noted.

“This [the new pooled analysis] will change that,” Dr. Smith predicted. “It does not apply to patients who were infirm prior to their stroke – but for patients who were otherwise healthy, with a modified Rankin scale level of 0 or 1 at initial presentation, it appears that they benefit [from thrombectomy] regardless of their age.” In the pooled analysis, 198 of the 1,287 total patients (15%) were at least 80 years old.

“It removes age discrimination. A healthy 80-year-old may do extremely well with this treatment,” Dr. Smith said.

The consistency of benefit across a wide range of stroke severity that showed up in the trials as four distinct strata of NIH Stroke Scale scores prior to treatment was another important finding that could not previously be definitively made by analyzing each of the five trials individually.

In patients with stroke-severity scores that ranged from 10 or less (the least severely affected) to patients with scores of 21 or greater, all had post-thrombectomy improvements that clustered around the overall average number-needed-to-treat of 2.6 patients to reduce the disability of one patient at follow-up by at least one level on the modified Rankin scale.

Other notable findings from the pooled analysis were that thrombectomy also produced a consistent benefit to patients across every other subgroup examined, including sex, specific occlusion site, whether or not patients also received thrombolytic treatment with tissue plasminogen activator, and time to thrombectomy treatment (5 or fewer hours from stroke onset or more than 5 hours), reported Dr. Michael D. Hill and Dr. Tudor G. Jovin in a joint presentation at the meeting, sponsored by the American Heart Association.

Their pooled analysis, known as HERMES, pooled data from the MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA trials, all run during 2010-2014.

“Endovascular treatment is a highly effective treatment across all subgroups,” concluded Dr. Hill and Dr. Jovin as they completed their talk. “These data may provide additional support for endovascular treatment in subgroups not addressed in the individual trials.”

Concurrent with their report at the meeting, the results appeared in a paper published online (Lancet. 2016 Feb 18;doi: 10.1016/S0140-6736(16)00163-X).

Both Dr. Jovin and Dr. Hill shared the enthusiasm of Dr. Smith and others in the packed meeting room about the age finding.

“Older patients seemed to benefit even more” from thrombectomy, compared with younger patients, noted Dr. Jovin, chief of the stroke division at the University of Pittsburgh and a coinvestigator on SWIFT PRIME. “There is no reason to deny this treatment to appropriately selected patients based on age,” he said.

“There is no upper age limit,” agreed Dr. Hill, professor of neurology and director of the stroke unit at the University of Calgary (Alta.) and a coinvestigator on the ESCAPE trial. “If it’s an otherwise healthy 90-year-old who is living independently, you can surely consider them for this treatment.”

HERMES received fundings through an unrestricted grant from Medtronic. Dr. Hill and Dr. Jovin had no personal disclosures. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker.

[email protected]

On Twitter @mitchelzoler

LOS ANGELES – Clot removal to recanalize the occluded intracerebral arteries of acute ischemic stroke patients was as effective for producing good outcomes in patients aged 80 years or older as it was in younger patients, according to results from a pooled analysis of 1,287 patients in five separate but similar randomized trials.

This unprecedented evidence for the safety and efficacy of thrombectomy (also known as embolectomy) in octogenarians experiencing an acute occlusive, large-vessel, proximal anterior-circulation stroke was one of several new findings from the pooled analysis that should help further push thrombectomy to the forefront of acute care for patients undergoing this type of ischemic stroke, predicted Dr. Wade S. Smith in a video interview at the International Stroke Conference.

“By looking at all the data, we have much more refined information on the robustness of the treatment across age groups, which is quite important, especially patients in the 80-plus age group,” commented Dr. Smith, professor of neurology and chief of the neurovascular division at the University of California, San Francisco.

Until now, during the year following the reports in early 2015 from all five studies, “age had been a limiting factor” in applying the practicing-changing intervention of thrombectomy to patients, he noted.

“This [the new pooled analysis] will change that,” Dr. Smith predicted. “It does not apply to patients who were infirm prior to their stroke – but for patients who were otherwise healthy, with a modified Rankin scale level of 0 or 1 at initial presentation, it appears that they benefit [from thrombectomy] regardless of their age.” In the pooled analysis, 198 of the 1,287 total patients (15%) were at least 80 years old.

“It removes age discrimination. A healthy 80-year-old may do extremely well with this treatment,” Dr. Smith said.

The consistency of benefit across a wide range of stroke severity that showed up in the trials as four distinct strata of NIH Stroke Scale scores prior to treatment was another important finding that could not previously be definitively made by analyzing each of the five trials individually.

In patients with stroke-severity scores that ranged from 10 or less (the least severely affected) to patients with scores of 21 or greater, all had post-thrombectomy improvements that clustered around the overall average number-needed-to-treat of 2.6 patients to reduce the disability of one patient at follow-up by at least one level on the modified Rankin scale.

Other notable findings from the pooled analysis were that thrombectomy also produced a consistent benefit to patients across every other subgroup examined, including sex, specific occlusion site, whether or not patients also received thrombolytic treatment with tissue plasminogen activator, and time to thrombectomy treatment (5 or fewer hours from stroke onset or more than 5 hours), reported Dr. Michael D. Hill and Dr. Tudor G. Jovin in a joint presentation at the meeting, sponsored by the American Heart Association.

Their pooled analysis, known as HERMES, pooled data from the MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA trials, all run during 2010-2014.

“Endovascular treatment is a highly effective treatment across all subgroups,” concluded Dr. Hill and Dr. Jovin as they completed their talk. “These data may provide additional support for endovascular treatment in subgroups not addressed in the individual trials.”

Concurrent with their report at the meeting, the results appeared in a paper published online (Lancet. 2016 Feb 18;doi: 10.1016/S0140-6736(16)00163-X).

Both Dr. Jovin and Dr. Hill shared the enthusiasm of Dr. Smith and others in the packed meeting room about the age finding.

“Older patients seemed to benefit even more” from thrombectomy, compared with younger patients, noted Dr. Jovin, chief of the stroke division at the University of Pittsburgh and a coinvestigator on SWIFT PRIME. “There is no reason to deny this treatment to appropriately selected patients based on age,” he said.

“There is no upper age limit,” agreed Dr. Hill, professor of neurology and director of the stroke unit at the University of Calgary (Alta.) and a coinvestigator on the ESCAPE trial. “If it’s an otherwise healthy 90-year-old who is living independently, you can surely consider them for this treatment.”

HERMES received fundings through an unrestricted grant from Medtronic. Dr. Hill and Dr. Jovin had no personal disclosures. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Surgeons can expect to see more abdominal organ transplant recipients presenting with aortic aneurysms, as transplant survival rates increase along with the age of organ donors and recipients.

“The consensus is that abdominal aortic aneurysms (AAAs) have a more aggressive course post-transplant and within that context, probably need to be managed more aggressively,” Dr. Michael J. Englesbe of the University of Michigan, Ann Arbor said at the annual Northwestern Vascular Symposium.

Some 270,000 Americans are living with a functioning liver or kidney graft, and their average age has risen from 47 years to 57 years over the last decade.

Though the data isn’t great, it’s hypothesized that the immunosuppression prerequisite for successful organ transplantation promotes the progression of atherosclerosis and aneurysm growth in transplant patients, he said.

New-onset diabetes, hyperlipidemia, and hypertension are all common post-transplant due to immunosuppression therapy. Aortic aneurysms are also reported to rupture at smaller sizes in transplant recipients.

Intriguingly, the opposite effect has been observed in experimental animal models, where immunosuppression with calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors has been shown to stabilize atherosclerotic lesions and inhibit aneurysm expansion.

The reason for this disparity is unclear, but immunosuppressants likely augment other cardiovascular comorbidities such as hypertension and atherosclerosis and this may trump their anti-inflammatory effects and lead to worse aneurysm disease and faster expansion in humans, Dr. Englesbe speculated in an interview.

As for when aneurysms should be fixed, kidney transplant candidates should undergo AAA repair prior to transplantation since the risk of renal complications after aneurysm repair puts the allograft at risk, Dr. Englesbe advised. Either an open or endovascular approach can be used.

In liver transplant candidates, elective AAA repair should be avoided if possible and is contraindicated if any signs of hepatic decompensation are present such as muscle wasting, ascites, platelet count less than 50 x 10⁹/L, or encephalopathy. For well-compensated cirrhotic patients, endovascular repair is best.

One of the most important considerations for any solid-organ transplant patient undergoing aneurysm repair is perioperative management of immunosuppression, Dr. Englesbe stressed.

Transplant patients are maintained on oral calcineurin inhibitors such as cyclosporine and tacrolimus (Prograf) throughout the perioperative period to prevent organ rejection, but these drugs have nephrotoxic effects. About 10% of recipients, typically the sicker patients, will be switched to mTOR inhibitors such as everolimus (Afinitor) and sirolumus (Rapamune) as a kidney-sparing alternative.

“Part of the mechanism of these [mTOR] drugs is that they really affect fibroblast functioning, so patients that are on these medications, their wound will fall apart and they will invariably get a hernia,” Dr. Englesbe said. “You have to stop them upwards of about 6 weeks before surgical intervention, and I think this is also true for many endografts.”

He highlighted a case in which an mTOR inhibitor was started three months after liver transplant due to renal dysfunction in a patient who was fully healed, but within three weeks, “her wound fell apart, completely fell apart.” She developed several seromas underneath her incision, one of which became infected and took months to close.

“The transplant professionals – your nephrologists, your cardiologists – aren’t going to know this fact, but as a transplant surgeon it’s usually the first question we’re going to ask with respect to any post-transplant patient we’re going to operate on, so it’s something to keep in mind,” Dr. Englesbe said.

Another take-home message was the importance of maintaining kidney function in kidney recipients presenting with aortic aneurysm, as mortality in these patients is about 10-fold higher once the kidney fails, he said. A recent study reported that AAAs are significantly more common in kidney than liver transplant recipients (29.6% vs. 11.4%; P = .02), despite a similar prevalence for any aneurysm (4%) in both groups (J Vasc Surg. 2014 Mar;59;594-8).

When kidney recipients present, preoperative imaging of the aorta from the aneurysm to the kidney allograft is mandatory, he said. Endovascular repair is preferred, whenever possible.

The renal graft is typically sewn to the external iliac artery 3 cm to 10 cm from the bifurcation of the external and internal iliac arteries. Because of this, repair is challenging when aneurysmal disease involves the iliac artery, Dr. Englesbe observed. Aneurysmal dilation is less common in the external iliac, but stenting an iliac aneurysm can still compromise inflow to the transplanted kidney.

Several surgical techniques including axillofemoral bypass, aortofemoral shunt, or extracorporeal circuit have been reported to preserve renal function during open AAA repair in renal transplant recipients. These techniques are not without their own risk of complications and should be avoided in patients with low creatinine, but are appropriate in patients with marginal or impaired renal function, according to Dr. Englesbe, who reported having no relevant disclosures.

CHICAGO – Surgeons can expect to see more abdominal organ transplant recipients presenting with aortic aneurysms, as transplant survival rates increase along with the age of organ donors and recipients.

“The consensus is that abdominal aortic aneurysms (AAAs) have a more aggressive course post-transplant and within that context, probably need to be managed more aggressively,” Dr. Michael J. Englesbe of the University of Michigan, Ann Arbor said at the annual Northwestern Vascular Symposium.

Some 270,000 Americans are living with a functioning liver or kidney graft, and their average age has risen from 47 years to 57 years over the last decade.

Though the data isn’t great, it’s hypothesized that the immunosuppression prerequisite for successful organ transplantation promotes the progression of atherosclerosis and aneurysm growth in transplant patients, he said.

New-onset diabetes, hyperlipidemia, and hypertension are all common post-transplant due to immunosuppression therapy. Aortic aneurysms are also reported to rupture at smaller sizes in transplant recipients.

Intriguingly, the opposite effect has been observed in experimental animal models, where immunosuppression with calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors has been shown to stabilize atherosclerotic lesions and inhibit aneurysm expansion.

The reason for this disparity is unclear, but immunosuppressants likely augment other cardiovascular comorbidities such as hypertension and atherosclerosis and this may trump their anti-inflammatory effects and lead to worse aneurysm disease and faster expansion in humans, Dr. Englesbe speculated in an interview.

As for when aneurysms should be fixed, kidney transplant candidates should undergo AAA repair prior to transplantation since the risk of renal complications after aneurysm repair puts the allograft at risk, Dr. Englesbe advised. Either an open or endovascular approach can be used.

In liver transplant candidates, elective AAA repair should be avoided if possible and is contraindicated if any signs of hepatic decompensation are present such as muscle wasting, ascites, platelet count less than 50 x 10⁹/L, or encephalopathy. For well-compensated cirrhotic patients, endovascular repair is best.

One of the most important considerations for any solid-organ transplant patient undergoing aneurysm repair is perioperative management of immunosuppression, Dr. Englesbe stressed.

Transplant patients are maintained on oral calcineurin inhibitors such as cyclosporine and tacrolimus (Prograf) throughout the perioperative period to prevent organ rejection, but these drugs have nephrotoxic effects. About 10% of recipients, typically the sicker patients, will be switched to mTOR inhibitors such as everolimus (Afinitor) and sirolumus (Rapamune) as a kidney-sparing alternative.

“Part of the mechanism of these [mTOR] drugs is that they really affect fibroblast functioning, so patients that are on these medications, their wound will fall apart and they will invariably get a hernia,” Dr. Englesbe said. “You have to stop them upwards of about 6 weeks before surgical intervention, and I think this is also true for many endografts.”

He highlighted a case in which an mTOR inhibitor was started three months after liver transplant due to renal dysfunction in a patient who was fully healed, but within three weeks, “her wound fell apart, completely fell apart.” She developed several seromas underneath her incision, one of which became infected and took months to close.

“The transplant professionals – your nephrologists, your cardiologists – aren’t going to know this fact, but as a transplant surgeon it’s usually the first question we’re going to ask with respect to any post-transplant patient we’re going to operate on, so it’s something to keep in mind,” Dr. Englesbe said.

Another take-home message was the importance of maintaining kidney function in kidney recipients presenting with aortic aneurysm, as mortality in these patients is about 10-fold higher once the kidney fails, he said. A recent study reported that AAAs are significantly more common in kidney than liver transplant recipients (29.6% vs. 11.4%; P = .02), despite a similar prevalence for any aneurysm (4%) in both groups (J Vasc Surg. 2014 Mar;59;594-8).

When kidney recipients present, preoperative imaging of the aorta from the aneurysm to the kidney allograft is mandatory, he said. Endovascular repair is preferred, whenever possible.

The renal graft is typically sewn to the external iliac artery 3 cm to 10 cm from the bifurcation of the external and internal iliac arteries. Because of this, repair is challenging when aneurysmal disease involves the iliac artery, Dr. Englesbe observed. Aneurysmal dilation is less common in the external iliac, but stenting an iliac aneurysm can still compromise inflow to the transplanted kidney.

Several surgical techniques including axillofemoral bypass, aortofemoral shunt, or extracorporeal circuit have been reported to preserve renal function during open AAA repair in renal transplant recipients. These techniques are not without their own risk of complications and should be avoided in patients with low creatinine, but are appropriate in patients with marginal or impaired renal function, according to Dr. Englesbe, who reported having no relevant disclosures.

CHICAGO – Surgeons can expect to see more abdominal organ transplant recipients presenting with aortic aneurysms, as transplant survival rates increase along with the age of organ donors and recipients.

“The consensus is that abdominal aortic aneurysms (AAAs) have a more aggressive course post-transplant and within that context, probably need to be managed more aggressively,” Dr. Michael J. Englesbe of the University of Michigan, Ann Arbor said at the annual Northwestern Vascular Symposium.

Some 270,000 Americans are living with a functioning liver or kidney graft, and their average age has risen from 47 years to 57 years over the last decade.

Though the data isn’t great, it’s hypothesized that the immunosuppression prerequisite for successful organ transplantation promotes the progression of atherosclerosis and aneurysm growth in transplant patients, he said.

New-onset diabetes, hyperlipidemia, and hypertension are all common post-transplant due to immunosuppression therapy. Aortic aneurysms are also reported to rupture at smaller sizes in transplant recipients.

Intriguingly, the opposite effect has been observed in experimental animal models, where immunosuppression with calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors has been shown to stabilize atherosclerotic lesions and inhibit aneurysm expansion.

The reason for this disparity is unclear, but immunosuppressants likely augment other cardiovascular comorbidities such as hypertension and atherosclerosis and this may trump their anti-inflammatory effects and lead to worse aneurysm disease and faster expansion in humans, Dr. Englesbe speculated in an interview.

As for when aneurysms should be fixed, kidney transplant candidates should undergo AAA repair prior to transplantation since the risk of renal complications after aneurysm repair puts the allograft at risk, Dr. Englesbe advised. Either an open or endovascular approach can be used.

In liver transplant candidates, elective AAA repair should be avoided if possible and is contraindicated if any signs of hepatic decompensation are present such as muscle wasting, ascites, platelet count less than 50 x 10⁹/L, or encephalopathy. For well-compensated cirrhotic patients, endovascular repair is best.

One of the most important considerations for any solid-organ transplant patient undergoing aneurysm repair is perioperative management of immunosuppression, Dr. Englesbe stressed.

Transplant patients are maintained on oral calcineurin inhibitors such as cyclosporine and tacrolimus (Prograf) throughout the perioperative period to prevent organ rejection, but these drugs have nephrotoxic effects. About 10% of recipients, typically the sicker patients, will be switched to mTOR inhibitors such as everolimus (Afinitor) and sirolumus (Rapamune) as a kidney-sparing alternative.

“Part of the mechanism of these [mTOR] drugs is that they really affect fibroblast functioning, so patients that are on these medications, their wound will fall apart and they will invariably get a hernia,” Dr. Englesbe said. “You have to stop them upwards of about 6 weeks before surgical intervention, and I think this is also true for many endografts.”

He highlighted a case in which an mTOR inhibitor was started three months after liver transplant due to renal dysfunction in a patient who was fully healed, but within three weeks, “her wound fell apart, completely fell apart.” She developed several seromas underneath her incision, one of which became infected and took months to close.

“The transplant professionals – your nephrologists, your cardiologists – aren’t going to know this fact, but as a transplant surgeon it’s usually the first question we’re going to ask with respect to any post-transplant patient we’re going to operate on, so it’s something to keep in mind,” Dr. Englesbe said.

Another take-home message was the importance of maintaining kidney function in kidney recipients presenting with aortic aneurysm, as mortality in these patients is about 10-fold higher once the kidney fails, he said. A recent study reported that AAAs are significantly more common in kidney than liver transplant recipients (29.6% vs. 11.4%; P = .02), despite a similar prevalence for any aneurysm (4%) in both groups (J Vasc Surg. 2014 Mar;59;594-8).

When kidney recipients present, preoperative imaging of the aorta from the aneurysm to the kidney allograft is mandatory, he said. Endovascular repair is preferred, whenever possible.

The renal graft is typically sewn to the external iliac artery 3 cm to 10 cm from the bifurcation of the external and internal iliac arteries. Because of this, repair is challenging when aneurysmal disease involves the iliac artery, Dr. Englesbe observed. Aneurysmal dilation is less common in the external iliac, but stenting an iliac aneurysm can still compromise inflow to the transplanted kidney.

Several surgical techniques including axillofemoral bypass, aortofemoral shunt, or extracorporeal circuit have been reported to preserve renal function during open AAA repair in renal transplant recipients. These techniques are not without their own risk of complications and should be avoided in patients with low creatinine, but are appropriate in patients with marginal or impaired renal function, according to Dr. Englesbe, who reported having no relevant disclosures.

CHICAGO – Adoption of an organized, systematic approach to ruptured abdominal aortic aneurysm has been inconsistent.

In a recent survey of vascular physicians in the western United States, 60% who accept ruptured abdominal aortic aneurysm (rAAA) transfers do not have a formal protocol for treatment and 70% do not use a transfer protocol or clinical guidelines (J Vasc Surg. 2015 Aug;62:326-30).

Guidelines for the management and transfer of patients with rAAA have been developed in the United Kingdom, but no such guidelines currently exist in the United States.

Patrice Wendling/Frontline Medical News

To address this disparity, the Western Vascular Society used the survey results, existing European guidelines, and a literature review to develop a set of 15 best practice steps for rAAA transfer. The “guidelines” were endorsed by the society members in September 2015 and are to be published early in 2016, Dr. Matthew Mell of Stanford (Calif.) University Medical Center said at a symposium on vascular surgery sponsored by Northwestern University. The guidelines identify four key components to a successful transfer: an organized inter-facility system of care including rapid triage and transport, defined clinical criteria for transfer, standard resuscitation protocols for the transport, and appropriate resources at the receiving hospital.

During transport, aim for a systolic blood pressure of 70 mm Hg to 90 mm Hg, establish peripheral intravenous access, and avoid aggressive fluid resuscitation, the guidelines advise. Blood products may delay the transfer.

Receiving hospitals should provide a simple and reliable method of referral and have formal protocols in place for the treatment of transferred patients.

Centers that receive patients should have endovascular aortic repair capabilities for ruptured aneurysms, including the ability to perform EVAR under local anesthesia, as well as appropriate facilities and expertise, Dr. Mell said. This advice is based mainly on outcomes observed in the IMPROVE trial (Br J Surg. 2014;101;216-24).

Successful programs tend to repair more than 20-25 ruptures per year, have on-site EVAR inventory, and, for the most part, have vascular surgeons able to perform dual open and endovascular repair. Hospital resources in these successful programs have a single phone number for transfer requests, electronic image transfer, immediately available blood products, hospital policy to accept all requests regardless of bed capacity, a contingency plan to create bed capacity after repair, and real-time management between the transfer center, bed control, and clinicians.

“This is really important because a lot of tertiary centers struggle with bed capacity if bottlenecked and a significant number [about one-third] of transfer requests are declined because of lack of capacity or dedicated room,” Dr. Mell said.

In a more recent study, nearly 20% of 4,439 patients who presented with rAAA in New York, California, and Florida were transferred for definitive care. Transfer rates rose yearly during the study period from 14% in 2005 to 22% in 2010 (J Vasc Surg. 2014;60:553-7).

“Transfer is increasingly utilized as a means for definitive care,” Dr. Mell said.

However, one in six of those transferred died without receiving treatment.

In adjusted analyses, inter-facility transfer was associated with significantly lower mortality when only patients receiving treatment were analyzed (adjusted odds ratio, 0.81; P = .02), but was actually associated with higher mortality when patients who died without treatment were also included (aOR, 1.30; P = .01).

“Outcomes after transfer can be improved by better patient selection and more efficient systems of care,” Dr. Mell concluded. “Guidelines may help; it’s too soon to know, but successful transfer programs require forethought, resources, and alignment of all stakeholders.”

Dr. Mell reported having no conflicts of interest.

CHICAGO – Adoption of an organized, systematic approach to ruptured abdominal aortic aneurysm has been inconsistent.

In a recent survey of vascular physicians in the western United States, 60% who accept ruptured abdominal aortic aneurysm (rAAA) transfers do not have a formal protocol for treatment and 70% do not use a transfer protocol or clinical guidelines (J Vasc Surg. 2015 Aug;62:326-30).

Guidelines for the management and transfer of patients with rAAA have been developed in the United Kingdom, but no such guidelines currently exist in the United States.

Patrice Wendling/Frontline Medical News

To address this disparity, the Western Vascular Society used the survey results, existing European guidelines, and a literature review to develop a set of 15 best practice steps for rAAA transfer. The “guidelines” were endorsed by the society members in September 2015 and are to be published early in 2016, Dr. Matthew Mell of Stanford (Calif.) University Medical Center said at a symposium on vascular surgery sponsored by Northwestern University. The guidelines identify four key components to a successful transfer: an organized inter-facility system of care including rapid triage and transport, defined clinical criteria for transfer, standard resuscitation protocols for the transport, and appropriate resources at the receiving hospital.

During transport, aim for a systolic blood pressure of 70 mm Hg to 90 mm Hg, establish peripheral intravenous access, and avoid aggressive fluid resuscitation, the guidelines advise. Blood products may delay the transfer.

Receiving hospitals should provide a simple and reliable method of referral and have formal protocols in place for the treatment of transferred patients.

Centers that receive patients should have endovascular aortic repair capabilities for ruptured aneurysms, including the ability to perform EVAR under local anesthesia, as well as appropriate facilities and expertise, Dr. Mell said. This advice is based mainly on outcomes observed in the IMPROVE trial (Br J Surg. 2014;101;216-24).

Successful programs tend to repair more than 20-25 ruptures per year, have on-site EVAR inventory, and, for the most part, have vascular surgeons able to perform dual open and endovascular repair. Hospital resources in these successful programs have a single phone number for transfer requests, electronic image transfer, immediately available blood products, hospital policy to accept all requests regardless of bed capacity, a contingency plan to create bed capacity after repair, and real-time management between the transfer center, bed control, and clinicians.

“This is really important because a lot of tertiary centers struggle with bed capacity if bottlenecked and a significant number [about one-third] of transfer requests are declined because of lack of capacity or dedicated room,” Dr. Mell said.

In a more recent study, nearly 20% of 4,439 patients who presented with rAAA in New York, California, and Florida were transferred for definitive care. Transfer rates rose yearly during the study period from 14% in 2005 to 22% in 2010 (J Vasc Surg. 2014;60:553-7).

“Transfer is increasingly utilized as a means for definitive care,” Dr. Mell said.

However, one in six of those transferred died without receiving treatment.

In adjusted analyses, inter-facility transfer was associated with significantly lower mortality when only patients receiving treatment were analyzed (adjusted odds ratio, 0.81; P = .02), but was actually associated with higher mortality when patients who died without treatment were also included (aOR, 1.30; P = .01).

“Outcomes after transfer can be improved by better patient selection and more efficient systems of care,” Dr. Mell concluded. “Guidelines may help; it’s too soon to know, but successful transfer programs require forethought, resources, and alignment of all stakeholders.”

Dr. Mell reported having no conflicts of interest.

CHICAGO – Adoption of an organized, systematic approach to ruptured abdominal aortic aneurysm has been inconsistent.

In a recent survey of vascular physicians in the western United States, 60% who accept ruptured abdominal aortic aneurysm (rAAA) transfers do not have a formal protocol for treatment and 70% do not use a transfer protocol or clinical guidelines (J Vasc Surg. 2015 Aug;62:326-30).

Guidelines for the management and transfer of patients with rAAA have been developed in the United Kingdom, but no such guidelines currently exist in the United States.

Patrice Wendling/Frontline Medical News

To address this disparity, the Western Vascular Society used the survey results, existing European guidelines, and a literature review to develop a set of 15 best practice steps for rAAA transfer. The “guidelines” were endorsed by the society members in September 2015 and are to be published early in 2016, Dr. Matthew Mell of Stanford (Calif.) University Medical Center said at a symposium on vascular surgery sponsored by Northwestern University. The guidelines identify four key components to a successful transfer: an organized inter-facility system of care including rapid triage and transport, defined clinical criteria for transfer, standard resuscitation protocols for the transport, and appropriate resources at the receiving hospital.

During transport, aim for a systolic blood pressure of 70 mm Hg to 90 mm Hg, establish peripheral intravenous access, and avoid aggressive fluid resuscitation, the guidelines advise. Blood products may delay the transfer.

Receiving hospitals should provide a simple and reliable method of referral and have formal protocols in place for the treatment of transferred patients.

Centers that receive patients should have endovascular aortic repair capabilities for ruptured aneurysms, including the ability to perform EVAR under local anesthesia, as well as appropriate facilities and expertise, Dr. Mell said. This advice is based mainly on outcomes observed in the IMPROVE trial (Br J Surg. 2014;101;216-24).

Successful programs tend to repair more than 20-25 ruptures per year, have on-site EVAR inventory, and, for the most part, have vascular surgeons able to perform dual open and endovascular repair. Hospital resources in these successful programs have a single phone number for transfer requests, electronic image transfer, immediately available blood products, hospital policy to accept all requests regardless of bed capacity, a contingency plan to create bed capacity after repair, and real-time management between the transfer center, bed control, and clinicians.

“This is really important because a lot of tertiary centers struggle with bed capacity if bottlenecked and a significant number [about one-third] of transfer requests are declined because of lack of capacity or dedicated room,” Dr. Mell said.

In a more recent study, nearly 20% of 4,439 patients who presented with rAAA in New York, California, and Florida were transferred for definitive care. Transfer rates rose yearly during the study period from 14% in 2005 to 22% in 2010 (J Vasc Surg. 2014;60:553-7).

“Transfer is increasingly utilized as a means for definitive care,” Dr. Mell said.

However, one in six of those transferred died without receiving treatment.

In adjusted analyses, inter-facility transfer was associated with significantly lower mortality when only patients receiving treatment were analyzed (adjusted odds ratio, 0.81; P = .02), but was actually associated with higher mortality when patients who died without treatment were also included (aOR, 1.30; P = .01).

“Outcomes after transfer can be improved by better patient selection and more efficient systems of care,” Dr. Mell concluded. “Guidelines may help; it’s too soon to know, but successful transfer programs require forethought, resources, and alignment of all stakeholders.”

Dr. Mell reported having no conflicts of interest.

Neurologic emergencies such as acute stroke, status epilepticus, subarachnoid hemorrhage, neuromuscular weakness, and spinal cord injury affect millions of Americans yearly.^1,2 These conditions can be difficult to diagnose, and delays in recognition and treatment can have devastating results. Consequently, it is important for nonneurologists to be able to quickly recognize these conditions and initiate timely management, often while awaiting neurologic consultation.

Here, we review how to recognize and treat these common, serious conditions.

ACUTE ISCHEMIC STROKE: TIME IS OF THE ESSENCE

Stroke is the fourth leading cause of death in the United States and is one of the most common causes of disability worldwide.^3–5 About 85% of strokes are ischemic, resulting from diminished vascular supply to the brain. Symptoms such as facial droop, unilateral weakness or numbness, aphasia, gaze deviation, and unsteadiness of gait may be seen. Time is of the essence, as all currently available interventions are safe and effective only within defined time windows.

Diagnosis and assessment

When acute ischemic stroke is suspected, the clinical history, time of onset, and basic neurologic examination should be obtained quickly.

The National Institutes of Health (NIH) stroke scale is an objective marker for assessing stroke severity as well as evolution of disease and should be obtained in all stroke patients. Scores range from 0 (best) to 42 (worst) (www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf).

Time of onset of symptoms is essential to determine, since it guides eligibility for acute therapies. Clinicians should ascertain the last time the patient was seen to be neurologically well in order to estimate this time window as closely as possible.

Laboratory tests should include a fingerstick blood glucose measurement, coagulation studies, complete blood cell count, and basic metabolic profile.

Computed tomography (CT) of the head without contrast should be obtained immediately to exclude acute hemorrhage and any alternative diagnoses that could explain the patient’s symptoms. Acute brain ischemia is often not apparent on CT during the first few hours of injury. Therefore, a patient presenting with new focal neurologic deficits and an unremarkable result on CT of the head should be treated as having had an acute ischemic stroke, and interventional therapies should be considered.

Stroke mimics should be considered and treated, as appropriate (Table 1).

Acute management of ischemic stroke

Acute treatment should not be delayed by obtaining chest radiography, inserting a Foley catheter, or obtaining an electrocardiogram. The longer the time that elapses before treatment, the worse the functional outcome, underscoring the need for rapid decision-making.^6–8

Lowering the head of the bed may provide benefit by promoting blood flow to ischemic brain tissue.⁹ However, this should not be done in patients with significantly elevated intracerebral pressure and concern for herniation.

Permissive hypertension (antihypertensive treatment only for blood pressure greater than 220/110 mm Hg) should be allowed per national guidelines to provide adequate perfusion to brain areas at risk of injury.¹⁰

Tissue plasminogen activator. Patients with ischemic stroke who present within 3 hours of symptom onset should be considered for intravenous administration of tissue plasminogen activator (tPA), a safe and effective therapy with nearly 2 decades of evidence to support its use.¹⁰ The treating physician should carefully review the risks and benefits of this therapy.

To receive tPA, the patient must have all of the following:

• Clinical diagnosis of ischemic stroke with measurable neurologic deficit
• Onset of symptoms within the past 3 hours
• Age 18 or older.

The patient must not have any of the following:

• Significant stroke within the past 3 months
• Severe traumatic head injury within the past 3 months
• History of significant intracerebral hemorrhage
• Previously ruptured arteriovenous malformation or intracranial aneurysm
• Central nervous system neoplasm
• Arterial puncture at a noncompressible site within the past 7 days
• Evidence of hemorrhage on CT of the head
• Evidence of ischemia in greater than 33% of the cerebral hemisphere on head CT
• History and symptoms strongly suggesting subarachnoid hemorrhage
• Persistent hypertension (systolic pressure ≥ 185 mm Hg or diastolic pressure ≥ 110 mm Hg)
• Evidence of acute significant bleeding (external or internal)
• Hypoglycemia—ie, serum glucose less than 50 mg/dL (< 2.8 mmol/L)
• Thrombocytopenia (platelet count < 100 × 10⁹/L)
• Significant coagulopathy (international normalized ratio > 1.7, prothrombin time > 15 seconds, or abnormally elevated activated partial thromboplastin time)
• Current use of a factor Xa inhibitor or direct thrombin inhibitor.

Relative contraindications:

• Minor or rapidly resolving symptoms
• Major surgery or trauma within the past 14 days
• Gastrointestinal or urinary tract bleeding within the past 21 days
• Myocardial infarction in the past 3 months
• Unruptured intracranial aneurysm
• Seizure occurring at stroke onset
• Pregnancy.

If these criteria are satisfied, tPA should be given at a dose of 0.9 mg/kg intravenously over 60 minutes. Ten percent  of the dose should be given as an initial bolus, followed by a constant infusion of the remaining 90% over 1 hour.

If tPA is given, the blood pressure must be kept lower than 185/110 mm Hg to minimize the risk of symptomatic intracerebral hemorrhage.

A subset of patients may benefit from receiving intravenous tPA between 3 and 4.5 hours after the onset of stroke symptoms. These include patients who are no more than 80 years old, who have not recently used oral anticoagulants, who do not have severe neurologic injury (ie, do not have NIH Stroke Scale scores > 25), and who do not have diabetes mellitus or a history of ischemic stroke.¹¹ Although many hospitals have such a protocol for tPA up to 4.5 hours after the onset of stroke symptoms, this time window is not currently approved by the US Food and Drug Administration.

Intra-arterial therapy. Based on recent trials, some patients may benefit further from intra-arterial thrombolysis or mechanical thrombectomy, both delivered during catheter-based cerebral angiography, independent of intravenous tPA administration.^12,13 These patients should be evaluated on a case-by-case basis by a neurologist and neurointerventional team. Time windows for these treatments generally extend to 6 hours from stroke onset and perhaps even longer in some situations (eg, basilar artery occlusion).

An antiplatelet agent should be started quickly in all stroke patients who do not receive tPA. Patients who receive tPA can begin receiving an antiplatelet agent 24 hours afterward.

Unfractionated heparin. There is no evidence to support the use of unfractionated heparin in most cases of acute ischemic stroke.¹⁰

Glucose control (in the range of 140–180 mg/dL) and fever control remain essential elements of post-acute stroke care to provide additional protection to the damaged brain.

For ischemic stroke due to atrial fibrillation

In ischemic stroke due to atrial fibrillation, early anticoagulation should be considered, based on the CHA₂DS₂-VASC risk of ischemic stroke vs the HAS-BLED risk of hemorrhage (calculators available at www.mdcalc.com).

In general, anticoagulation may be withheld during the first 72 hours while further stroke workup and evaluation of extent of injury are carried out, as there is an increased risk of hemorrhagic transformation of the ischemic stroke. Often, anticoagulation is resumed at a full dose between 72 hours and 2 weeks of the ischemic stroke.

ACUTE HEMORRHAGIC STROKE: BLOOD PRESSURE, COAGULATION

Approximately 15% of strokes are caused by intracerebral hemorrhage, which can be detected with noncontrast head CT with a sensitivity of 98.6% within 6 hours of the onset of bleeding.¹⁴ A common underlying cause of intracerebral hemorrhage is chronic poorly controlled hypertension, causing rupture of damaged (or “lipohyalinized”) vessels with resultant blood extravasation into the brain parenchyma. Other causes are less common (Table 2).

Treatment of acute hemorrhagic stroke

Acute treatment of intracerebral hemorrhage includes blood pressure control, reversal of underlying coagulopathy or anticoagulation, and sometimes intracranial pressure control. There is little role for surgery in most cases, based on findings of randomized trials.¹⁵

Blood pressure control. Many studies have investigated optimal blood pressure goals in acute intracerebral hemorrhage. Recent data suggest that early aggressive therapy, targeting a systolic blood pressure goal less than 140 mm Hg within the first hour, is safe and can lead to better functional outcomes than a more conservative blood-pressure-lowering target.¹⁶ Rapid-onset, short-acting antihypertensive agents in intravenous form, such as nicardipine and labetalol, are frequently used. Of note, this treatment strategy for hemorrhagic stroke is in direct contrast to the treatment of ischemic stroke, in which permissive hypertension (blood pressure goal < 220/110 mm Hg) is often pursued.

Reversal of any coagulation abnormalities should be done quickly in intracranial hemorrhage. Warfarin use has been shown to be a strong independent predictor of intracranial hemorrhage expansion, which increases the risk of death.^17,18

Increasingly, agents other than vitamin K or fresh-frozen plasma are being used to rapidly reverse anticoagulation, including prothrombin complex concentrate (available in three- and four-factor preparations) and recombinant factor VIIa. While four-factor prothrombin complex concentrate and recombinant factor VIIa have been shown to be more efficacious than fresh-frozen plasma, there are limited data directly comparing these newer reversal agents against each other.¹⁹ The use of these medications is limited by availability and practitioner familiarity.^20–22

Reversing anticoagulation due to target-specific oral anticoagulants. The acute management of intracranial hemorrhage in patients taking the new target-specific oral anticoagulants (eg, dabigatran, apixaban, rivaroxaban, edoxaban) remains challenging. Laboratory tests such as factor Xa levels are not readily available in many institutions and do not provide results in a timely fashion, and in the interim, acute hemorrhage and clinical deterioration may occur. Management strategies involve giving fresh-frozen plasma, prothrombin complex concentrate, and consideration of hemodialysis.²³ Dabigatran reversal with idarucizumab has recently been shown to have efficacy.²⁴

Vigilance for elevated intracranial pressure. Intracranial hemorrhage can occasionally cause elevated intracranial pressure, which should be treated rapidly. Any acute decline in mental status in a patient with intracranial hemorrhage requires emergency imaging to evaluate for expansion of hemorrhage.

SUBARACHNOID HEMORRHAGE

The sudden onset of a “thunderclap” headache (often described by patients as “the worst headache of my life”) suggests subarachnoid hemorrhage.

In contrast to intracranial hemorrhage, in subarachnoid hemorrhage blood collects mainly in the cerebral spinal fluid-containing spaces surrounding the brain, leading to a higher incidence of hydrocephalus from impaired drainage of cerebrospinal fluid. Nontraumatic subarachnoid hemorrhage is most often caused by rupture of an intracranial aneurysm, which can be a devastating event, with death rates approaching 50%.²⁵

Diagnosis of subarachnoid hemorrhage

Noncontrast CT of the head is the main modality for diagnosing subarachnoid hemorrhage. Blood within the subarachnoid space is demonstrable in 92% of cases if CT is performed within the first 24 hours of hemorrhage, with an initial sensitivity of about 95% within the first 6 hours of onset.^14,26,27 The longer CT is delayed, the lower the sensitivity.

Some studies suggest that a protocol of CT followed by CT angiography can safely exclude aneurysmal subarachnoid hemorrhage and obviate the need for lumbar puncture. However, further research is required to validate this approach.²⁸

Lumbar puncture. If clinical suspicion of subarachnoid hemorrhage remains strong even though initial CT is negative, lumbar puncture must be performed for cerebrospinal fluid analysis.²⁹ Xanthochromia (a yellowish pigmentation of the cerebrospinal fluid due to the degeneration of blood products that occurs within 8 to 12 hours of bleeding) should raise the alarm for subarachnoid hemorrhage; this sign may be present up to 4 weeks after the bleeding event.³⁰

If lumbar puncture is contraindicated, then aneurysmal subarachnoid hemorrhage has not been ruled out, and further neurologic consultation should be pursued.

Management of subarachnoid hemorrhage

Early management of blood pressure for a ruptured intracranial aneurysm follows strategies similar to those for intracranial hemorrhage. Further investigation is rapidly directed toward an underlying vascular malformation, with intracranial vessel imaging such as CT angiography, magnetic resonance angiography, or the gold standard test—catheter-based cerebral angiography.

Aneurysms are treated (or “secured”) either by surgical clipping or by endovascular coiling. Endovascular coiling is preferable in cases in which both can be safely attempted.³¹ If the facility lacks the resources to do these procedures, the patient should be referred to a nearby tertiary care center.

INTRACRANIAL HYPERTENSION: DANGER OF BRAIN HERNIATION

A number of conditions can cause an acute intracranial pressure elevation. The danger of brain herniation requires that therapies be implemented rapidly to prevent catastrophic neurologic injury. In many situations, nonneurologists are the first responders and therefore should be familiar with basic intracranial pressure management.

Initial symptoms of acute rise in intracranial pressure

As intracranial pressure rises, pressure is typically equally distributed throughout the cranial vault, leading to dysfunction of the ascending reticular activating system, which clinically manifests as the inability to stay alert despite varying degrees of noxious stimulation. Progressive cranial neuropathies (often starting with pupillary abnormalities) and coma are often seen in this setting as the upper brainstem begins to be compressed.

Initial assessment and treatment of elevated intracranial pressure

Noncontrast CT of the head is often obtained immediately when acutely elevated intracranial pressure is suspected. If clinical examination and radiographic findings are consistent with intracranial hypertension, prompt measures can be started at the bedside.

Elevate the head of the bed to 30 degrees to promote venous drainage and reduce intracranial pressure. (In contrast, most other hemodynamically unstable patients are placed flat or in the Trendelenburg position.)

Intubation should be done quickly in cases of airway compromise, and hyperventilation should be started with a goal Paco₂ of 30 to 35 mm Hg. This hypocarbic strategy promotes cerebral vasoconstriction and a transient decrease in intracranial pressure.

Hyperosmolar therapy allows for transient intracranial volume decompression and is the mainstay of emergency medical treatment of intracranial hypertension. Mannitol is a hyper­osmolar polysaccharide that promotes osmotic diuresis and removes excessive cerebral water. In the acute setting, it can be given as an intravenous bolus of 1 to 2 g/kg through a peripheral intravenous line, followed by a bolus every 4 to 6 hours. Hypotension can occur after diuresis, and renal function should be closely monitored since frequent mannitol use can promote acute tubular necrosis. In patients who are anuric, the medication is typically not used.

Hypertonic saline (typically 3% sodium chloride, though different concentrations are available) is an alternative that helps draw interstitial fluid into the intravascular space, decreasing cerebral edema and maintaining hemodynamic stability. Relative contraindications include congestive heart failure or renal failure leading to pulmonary edema from volume overload. Hypertonic saline can be given as a bolus or a constant infusion. Some institutions have rapid access to 23.4% saline, which can be given as a 30-mL bolus but typically requires a central venous catheter for rapid infusion.

Comatose patients with radiographic findings of hydrocephalus, epidural or subdural hematoma, or mass effect with midline shift warrant prompt neurosurgical consultation for further surgical measures of intracranial pressure control and monitoring.

The ‘blown’ pupil

The physician should be concerned about elevated intracranial pressure if a patient has mydriasis, ie, an abnormally dilated (“blown”) pupil, which is a worrisome sign in the setting of true intracranial hypertension. However, many different processes can cause mydriasis and should be kept in mind when evaluating this finding (Table 3).³² If radiographic findings do not suggest elevated intracranial pressure, further workup into these other processes should be pursued.

STATUS EPILEPTICUS: SEIZURE CONTROL IS IMPORTANT

A continuous unremitting seizure lasting longer than 5 minutes or recurrent seizure activity in a patient who does not regain consciousness between seizures should be treated as status epilepticus. All seizure types carry the risk of progressing to status epilepticus, and responsiveness to antiepileptic drug therapy is inversely related to the duration of seizures. It is imperative that seizure activity be treated early and aggressively to prevent recalcitrant seizure activity, neuronal damage, and progression to status epilepticus.³³

Once the ABCs of emergency stabilization have been performed (ie, airway, breathing, circulation), antiepileptic drug therapy should start immediately using established algorithms (Figure 1).^34–36 During the course of treatment, the reliability of the neurologic examination may be limited due to medication effects or continued status epilepticus, making continuous video electroencephalographic monitoring often necessary to guide further therapy in patients who are not rapidly recovering.^34–38

Once status epilepticus has resolved, further investigation into the underlying cause should be pursued quickly, especially in patients without a previous diagnosis of epilepsy. Head CT with contrast or magnetic resonance imaging can be used to look for any structural abnormality that may explain seizures. Basic laboratory tests including toxicology screening can identify a common trigger such as hypoglycemia or stimulant use. Fever or other possible signs of meningitis should be investigated further with cerebrospinal fluid analysis.

SPINAL CORD INJURY

Acute spinal cord injury can lead to substantial long-term neurologic impairment and should be suspected in any patient presenting with focal motor loss, sensory loss, or both with sparing of the cranial nerves and mental status. Causes of injury include compression (traumatic or nontraumatic) and inflammatory and noninflammatory myelopathies.

The location of the injury can be inferred by analyzing the symptoms, which can point to the cord level and indicate whether the anterior or posterior of the cord is involved. Anterior cord injury tends to affect the descending corticospinal and pyramidal tracts, resulting in motor deficits and weakness. Posterior cord injury involves the dorsal columns, leading to deficits of vibration sensation and proprioception. High cervical cord injuries tend to involve varying degrees of quadriparesis, sensory loss, and sometimes respiratory compromise. A clinical history of bilateral lower-extremity weakness, a “band-like” sensory complaint around the lower chest or abdomen, or both, can suggest thoracic cord involvement. Symptoms isolated to one or both lower extremities along with lower back pain and bowel or bladder involvement may point to injury of the lumbosacral cord.

Basic management of spinal cord injury includes decompression of the bladder and initial protection against further injury with a stabilizing collar or brace.

Magnetic resonance imaging with and without contrast is the ideal study to evaluate injuries to the spinal cord itself. While CT is helpful in identifying bony disease of the spinal column (eg, evaluating traumatic fractures), it is not helpful in viewing intrinsic cord pathology.

Traumatic myelopathy

Traumatic spinal cord injury is usually suggested by the clinical history and confirmed with CT. In this setting, early consultation with a neurosurgeon is required to prevent permanent cord injury.

Guidelines suggest maintaining a mean arterial pressure greater than 85 to 90 mm Hg for the first 7 days after traumatic spinal cord injury, a particular problem in the setting of hemodynamic instability, which can accompany lesions above the midthoracic level.^39,40

Patients with vertebral body misalignment should be placed in an appropriate stabilizing collar or brace until a medically trained professional deems it appropriate to discontinue the device, or until surgical stabilization is performed.

Methylprednisone is a controversial intervention for acute spinal cord trauma, lacking clear benefit in meta-analyses.⁴¹

Nontraumatic compressive myelopathy

Patients with nontraumatic compressive myelopathy tend to present with varying degrees of back pain and worsening sensorimotor function. The differential diagnosis includes epidural abscesses, hematoma, metastatic neoplasm, and osteophyte compression (Table 4). The clinical history helps to guide therapy and should involve assessment for previous spinal column injury, immunocompromised state, travel history (which provides information on risks of exposure to a variety of diseases, including infections), and constitutional symptoms such as fever and weight loss.

Epidural abscess can have devastating results if missed. Red flags such as recent illness, intravenous drug use, focal back pain, fever, worsening numbness or weakness, and bowel or bladder incontinence should raise suspicion of this disorder. Emergency magnetic resonance imaging is required to diagnose this condition, and treatment involves urgent administration of antibiotics and consideration of surgical drainage.

Noncompressive myelopathies

There are numerous causes of noncompressive spinal cord injury (Table 4), and the etiology may be inflammatory (eg, “myelitis”) or noninflammatory. The diagnostic workup may require both magnetic resonance imaging and cerebrospinal fluid analysis. Acute disease-targeted therapy is rarely indicated and can be deferred until a full diagnostic workup has been completed.

NEUROMUSCULAR DISEASE: IS VENTILATION NEEDED?

Diseases involving the motor components of the peripheral nervous system (Table 5) share the common risk of causing ventilatory failure due to weakness of the diaphragm, intercostal muscles, and upper-airway muscles. Clinicians need to be aware of this risk and view these disorders as neurologic emergencies.

Determining when these patients require mechanical intubation is a challenge. Serial measurements of maximum inspiratory force and vital capacity are important and can be accomplished quickly at the bedside by a respiratory therapist. A maximum inspiratory force less than –30 cm H₂O or a vital capacity less than 20 mL/kg, or both, are worrisome markers that raise concern for impending ventilatory failure. Serial measurements can detect changes in these values that might indicate the need for elective intubation. In any patient presenting with weakness of the limbs, these measurements are an important step in the initial evaluation.

Myasthenic crisis

Myasthenia gravis is caused by autoantibodies directed against postsynaptic acetylcholine receptors. Patients demonstrate muscle weakness, usually in a proximal pattern, with fatigue, respiratory distress, nasal speech, ophthalmoparesis, and dysphagia. Exacerbations can occur as a response to recent infection, surgery, or medications such as neuromuscular blocking agents or aminoglycosides.

Myasthenic crisis, while uncommon, is a life-threatening emergency characterized by bulbar or respiratory failure secondary to muscle weakness. It can occur in patients already diagnosed with myasthenia gravis or may be the initial manifestation of the disease.^42–49 Intubation and mechanical ventilation are frequently required. Postoperative myasthenic patients in whom extubation has been delayed more than 24 hours should be considered in crisis.⁴⁵

The diagnosis of myasthenia gravis can be made by serum autoantibody testing, electromyography, and nerve conduction studies (with repetitive stimulation) or administration of edrophonium in patients with obvious ptosis.

The mainstay of therapy for myasthenic crisis is either intravenous immunoglobulin at a dose of 2 g/kg over 2 to 5 days or plasmapheresis (5–7 exchanges over 7–14 days). Corticosteroids are not recommended in myasthenic crisis in patients who are not intubated, as they can potentiate an initial worsening of crisis. Once the patient begins to show clinical improvement, outpatient pyridostigmine and immunosuppressive medications can be resumed at a low dose and titrated as tolerated.

Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome)

Acute inflammatory demyelinating polyneuropathy is an autoimmune disorder involving autoantibodies against axons or myelin in the peripheral nervous system.

This disease should be suspected in a patient who is developing worsening muscle weakness (usually with areflexia) over the course of days to weeks. Occasionally, a recent diarrheal or other systemic infectious trigger can be identified. Blood pressure instability and cardiac arrhythmia can also be seen due to autonomic nerve involvement. Although classically described as an “ascending paralysis,” other variants of this disease have distinct clinical presentations (eg, the descending paralysis, ataxia, areflexia, ophthalmoparesis of the Miller Fisher syndrome).

Acute inflammatory demyelinating polyneuropathy is diagnosed by electromyography and nerve conduction studies. A cerebrospinal fluid profile demonstrating elevated protein and few white blood cells is typical.

Treatment, as in myasthenic crisis, involves intravenous immunoglobulin or plasmapheresis. Corticosteroids are ineffective. Anticipation of ventilatory failure and expectant intubation is essential, given the progressive nature of the disorder.⁵⁰

Neurologic emergencies such as acute stroke, status epilepticus, subarachnoid hemorrhage, neuromuscular weakness, and spinal cord injury affect millions of Americans yearly.^1,2 These conditions can be difficult to diagnose, and delays in recognition and treatment can have devastating results. Consequently, it is important for nonneurologists to be able to quickly recognize these conditions and initiate timely management, often while awaiting neurologic consultation.

Here, we review how to recognize and treat these common, serious conditions.

ACUTE ISCHEMIC STROKE: TIME IS OF THE ESSENCE

Stroke is the fourth leading cause of death in the United States and is one of the most common causes of disability worldwide.^3–5 About 85% of strokes are ischemic, resulting from diminished vascular supply to the brain. Symptoms such as facial droop, unilateral weakness or numbness, aphasia, gaze deviation, and unsteadiness of gait may be seen. Time is of the essence, as all currently available interventions are safe and effective only within defined time windows.

Diagnosis and assessment

When acute ischemic stroke is suspected, the clinical history, time of onset, and basic neurologic examination should be obtained quickly.

The National Institutes of Health (NIH) stroke scale is an objective marker for assessing stroke severity as well as evolution of disease and should be obtained in all stroke patients. Scores range from 0 (best) to 42 (worst) (www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf).

Time of onset of symptoms is essential to determine, since it guides eligibility for acute therapies. Clinicians should ascertain the last time the patient was seen to be neurologically well in order to estimate this time window as closely as possible.

Laboratory tests should include a fingerstick blood glucose measurement, coagulation studies, complete blood cell count, and basic metabolic profile.

Computed tomography (CT) of the head without contrast should be obtained immediately to exclude acute hemorrhage and any alternative diagnoses that could explain the patient’s symptoms. Acute brain ischemia is often not apparent on CT during the first few hours of injury. Therefore, a patient presenting with new focal neurologic deficits and an unremarkable result on CT of the head should be treated as having had an acute ischemic stroke, and interventional therapies should be considered.

Stroke mimics should be considered and treated, as appropriate (Table 1).

Acute management of ischemic stroke

Acute treatment should not be delayed by obtaining chest radiography, inserting a Foley catheter, or obtaining an electrocardiogram. The longer the time that elapses before treatment, the worse the functional outcome, underscoring the need for rapid decision-making.^6–8

Lowering the head of the bed may provide benefit by promoting blood flow to ischemic brain tissue.⁹ However, this should not be done in patients with significantly elevated intracerebral pressure and concern for herniation.

Permissive hypertension (antihypertensive treatment only for blood pressure greater than 220/110 mm Hg) should be allowed per national guidelines to provide adequate perfusion to brain areas at risk of injury.¹⁰

Tissue plasminogen activator. Patients with ischemic stroke who present within 3 hours of symptom onset should be considered for intravenous administration of tissue plasminogen activator (tPA), a safe and effective therapy with nearly 2 decades of evidence to support its use.¹⁰ The treating physician should carefully review the risks and benefits of this therapy.

To receive tPA, the patient must have all of the following:

• Clinical diagnosis of ischemic stroke with measurable neurologic deficit
• Onset of symptoms within the past 3 hours
• Age 18 or older.

The patient must not have any of the following:

• Significant stroke within the past 3 months
• Severe traumatic head injury within the past 3 months
• History of significant intracerebral hemorrhage
• Previously ruptured arteriovenous malformation or intracranial aneurysm
• Central nervous system neoplasm
• Arterial puncture at a noncompressible site within the past 7 days
• Evidence of hemorrhage on CT of the head
• Evidence of ischemia in greater than 33% of the cerebral hemisphere on head CT
• History and symptoms strongly suggesting subarachnoid hemorrhage
• Persistent hypertension (systolic pressure ≥ 185 mm Hg or diastolic pressure ≥ 110 mm Hg)
• Evidence of acute significant bleeding (external or internal)
• Hypoglycemia—ie, serum glucose less than 50 mg/dL (< 2.8 mmol/L)
• Thrombocytopenia (platelet count < 100 × 10⁹/L)
• Significant coagulopathy (international normalized ratio > 1.7, prothrombin time > 15 seconds, or abnormally elevated activated partial thromboplastin time)
• Current use of a factor Xa inhibitor or direct thrombin inhibitor.

Relative contraindications:

• Minor or rapidly resolving symptoms
• Major surgery or trauma within the past 14 days
• Gastrointestinal or urinary tract bleeding within the past 21 days
• Myocardial infarction in the past 3 months
• Unruptured intracranial aneurysm
• Seizure occurring at stroke onset
• Pregnancy.

If these criteria are satisfied, tPA should be given at a dose of 0.9 mg/kg intravenously over 60 minutes. Ten percent  of the dose should be given as an initial bolus, followed by a constant infusion of the remaining 90% over 1 hour.

If tPA is given, the blood pressure must be kept lower than 185/110 mm Hg to minimize the risk of symptomatic intracerebral hemorrhage.

A subset of patients may benefit from receiving intravenous tPA between 3 and 4.5 hours after the onset of stroke symptoms. These include patients who are no more than 80 years old, who have not recently used oral anticoagulants, who do not have severe neurologic injury (ie, do not have NIH Stroke Scale scores > 25), and who do not have diabetes mellitus or a history of ischemic stroke.¹¹ Although many hospitals have such a protocol for tPA up to 4.5 hours after the onset of stroke symptoms, this time window is not currently approved by the US Food and Drug Administration.

Intra-arterial therapy. Based on recent trials, some patients may benefit further from intra-arterial thrombolysis or mechanical thrombectomy, both delivered during catheter-based cerebral angiography, independent of intravenous tPA administration.^12,13 These patients should be evaluated on a case-by-case basis by a neurologist and neurointerventional team. Time windows for these treatments generally extend to 6 hours from stroke onset and perhaps even longer in some situations (eg, basilar artery occlusion).

An antiplatelet agent should be started quickly in all stroke patients who do not receive tPA. Patients who receive tPA can begin receiving an antiplatelet agent 24 hours afterward.

Unfractionated heparin. There is no evidence to support the use of unfractionated heparin in most cases of acute ischemic stroke.¹⁰

Glucose control (in the range of 140–180 mg/dL) and fever control remain essential elements of post-acute stroke care to provide additional protection to the damaged brain.

For ischemic stroke due to atrial fibrillation

In ischemic stroke due to atrial fibrillation, early anticoagulation should be considered, based on the CHA₂DS₂-VASC risk of ischemic stroke vs the HAS-BLED risk of hemorrhage (calculators available at www.mdcalc.com).

In general, anticoagulation may be withheld during the first 72 hours while further stroke workup and evaluation of extent of injury are carried out, as there is an increased risk of hemorrhagic transformation of the ischemic stroke. Often, anticoagulation is resumed at a full dose between 72 hours and 2 weeks of the ischemic stroke.

ACUTE HEMORRHAGIC STROKE: BLOOD PRESSURE, COAGULATION

Approximately 15% of strokes are caused by intracerebral hemorrhage, which can be detected with noncontrast head CT with a sensitivity of 98.6% within 6 hours of the onset of bleeding.¹⁴ A common underlying cause of intracerebral hemorrhage is chronic poorly controlled hypertension, causing rupture of damaged (or “lipohyalinized”) vessels with resultant blood extravasation into the brain parenchyma. Other causes are less common (Table 2).

Treatment of acute hemorrhagic stroke

Acute treatment of intracerebral hemorrhage includes blood pressure control, reversal of underlying coagulopathy or anticoagulation, and sometimes intracranial pressure control. There is little role for surgery in most cases, based on findings of randomized trials.¹⁵

Blood pressure control. Many studies have investigated optimal blood pressure goals in acute intracerebral hemorrhage. Recent data suggest that early aggressive therapy, targeting a systolic blood pressure goal less than 140 mm Hg within the first hour, is safe and can lead to better functional outcomes than a more conservative blood-pressure-lowering target.¹⁶ Rapid-onset, short-acting antihypertensive agents in intravenous form, such as nicardipine and labetalol, are frequently used. Of note, this treatment strategy for hemorrhagic stroke is in direct contrast to the treatment of ischemic stroke, in which permissive hypertension (blood pressure goal < 220/110 mm Hg) is often pursued.

Reversal of any coagulation abnormalities should be done quickly in intracranial hemorrhage. Warfarin use has been shown to be a strong independent predictor of intracranial hemorrhage expansion, which increases the risk of death.^17,18

Increasingly, agents other than vitamin K or fresh-frozen plasma are being used to rapidly reverse anticoagulation, including prothrombin complex concentrate (available in three- and four-factor preparations) and recombinant factor VIIa. While four-factor prothrombin complex concentrate and recombinant factor VIIa have been shown to be more efficacious than fresh-frozen plasma, there are limited data directly comparing these newer reversal agents against each other.¹⁹ The use of these medications is limited by availability and practitioner familiarity.^20–22

Reversing anticoagulation due to target-specific oral anticoagulants. The acute management of intracranial hemorrhage in patients taking the new target-specific oral anticoagulants (eg, dabigatran, apixaban, rivaroxaban, edoxaban) remains challenging. Laboratory tests such as factor Xa levels are not readily available in many institutions and do not provide results in a timely fashion, and in the interim, acute hemorrhage and clinical deterioration may occur. Management strategies involve giving fresh-frozen plasma, prothrombin complex concentrate, and consideration of hemodialysis.²³ Dabigatran reversal with idarucizumab has recently been shown to have efficacy.²⁴

Vigilance for elevated intracranial pressure. Intracranial hemorrhage can occasionally cause elevated intracranial pressure, which should be treated rapidly. Any acute decline in mental status in a patient with intracranial hemorrhage requires emergency imaging to evaluate for expansion of hemorrhage.

SUBARACHNOID HEMORRHAGE

The sudden onset of a “thunderclap” headache (often described by patients as “the worst headache of my life”) suggests subarachnoid hemorrhage.

In contrast to intracranial hemorrhage, in subarachnoid hemorrhage blood collects mainly in the cerebral spinal fluid-containing spaces surrounding the brain, leading to a higher incidence of hydrocephalus from impaired drainage of cerebrospinal fluid. Nontraumatic subarachnoid hemorrhage is most often caused by rupture of an intracranial aneurysm, which can be a devastating event, with death rates approaching 50%.²⁵

Diagnosis of subarachnoid hemorrhage

Noncontrast CT of the head is the main modality for diagnosing subarachnoid hemorrhage. Blood within the subarachnoid space is demonstrable in 92% of cases if CT is performed within the first 24 hours of hemorrhage, with an initial sensitivity of about 95% within the first 6 hours of onset.^14,26,27 The longer CT is delayed, the lower the sensitivity.

Some studies suggest that a protocol of CT followed by CT angiography can safely exclude aneurysmal subarachnoid hemorrhage and obviate the need for lumbar puncture. However, further research is required to validate this approach.²⁸

Lumbar puncture. If clinical suspicion of subarachnoid hemorrhage remains strong even though initial CT is negative, lumbar puncture must be performed for cerebrospinal fluid analysis.²⁹ Xanthochromia (a yellowish pigmentation of the cerebrospinal fluid due to the degeneration of blood products that occurs within 8 to 12 hours of bleeding) should raise the alarm for subarachnoid hemorrhage; this sign may be present up to 4 weeks after the bleeding event.³⁰

If lumbar puncture is contraindicated, then aneurysmal subarachnoid hemorrhage has not been ruled out, and further neurologic consultation should be pursued.

Management of subarachnoid hemorrhage

Early management of blood pressure for a ruptured intracranial aneurysm follows strategies similar to those for intracranial hemorrhage. Further investigation is rapidly directed toward an underlying vascular malformation, with intracranial vessel imaging such as CT angiography, magnetic resonance angiography, or the gold standard test—catheter-based cerebral angiography.

Aneurysms are treated (or “secured”) either by surgical clipping or by endovascular coiling. Endovascular coiling is preferable in cases in which both can be safely attempted.³¹ If the facility lacks the resources to do these procedures, the patient should be referred to a nearby tertiary care center.

INTRACRANIAL HYPERTENSION: DANGER OF BRAIN HERNIATION

A number of conditions can cause an acute intracranial pressure elevation. The danger of brain herniation requires that therapies be implemented rapidly to prevent catastrophic neurologic injury. In many situations, nonneurologists are the first responders and therefore should be familiar with basic intracranial pressure management.

Initial symptoms of acute rise in intracranial pressure

As intracranial pressure rises, pressure is typically equally distributed throughout the cranial vault, leading to dysfunction of the ascending reticular activating system, which clinically manifests as the inability to stay alert despite varying degrees of noxious stimulation. Progressive cranial neuropathies (often starting with pupillary abnormalities) and coma are often seen in this setting as the upper brainstem begins to be compressed.

Initial assessment and treatment of elevated intracranial pressure

Noncontrast CT of the head is often obtained immediately when acutely elevated intracranial pressure is suspected. If clinical examination and radiographic findings are consistent with intracranial hypertension, prompt measures can be started at the bedside.

Elevate the head of the bed to 30 degrees to promote venous drainage and reduce intracranial pressure. (In contrast, most other hemodynamically unstable patients are placed flat or in the Trendelenburg position.)

Intubation should be done quickly in cases of airway compromise, and hyperventilation should be started with a goal Paco₂ of 30 to 35 mm Hg. This hypocarbic strategy promotes cerebral vasoconstriction and a transient decrease in intracranial pressure.

Hyperosmolar therapy allows for transient intracranial volume decompression and is the mainstay of emergency medical treatment of intracranial hypertension. Mannitol is a hyper­osmolar polysaccharide that promotes osmotic diuresis and removes excessive cerebral water. In the acute setting, it can be given as an intravenous bolus of 1 to 2 g/kg through a peripheral intravenous line, followed by a bolus every 4 to 6 hours. Hypotension can occur after diuresis, and renal function should be closely monitored since frequent mannitol use can promote acute tubular necrosis. In patients who are anuric, the medication is typically not used.

Hypertonic saline (typically 3% sodium chloride, though different concentrations are available) is an alternative that helps draw interstitial fluid into the intravascular space, decreasing cerebral edema and maintaining hemodynamic stability. Relative contraindications include congestive heart failure or renal failure leading to pulmonary edema from volume overload. Hypertonic saline can be given as a bolus or a constant infusion. Some institutions have rapid access to 23.4% saline, which can be given as a 30-mL bolus but typically requires a central venous catheter for rapid infusion.

Comatose patients with radiographic findings of hydrocephalus, epidural or subdural hematoma, or mass effect with midline shift warrant prompt neurosurgical consultation for further surgical measures of intracranial pressure control and monitoring.

The ‘blown’ pupil

The physician should be concerned about elevated intracranial pressure if a patient has mydriasis, ie, an abnormally dilated (“blown”) pupil, which is a worrisome sign in the setting of true intracranial hypertension. However, many different processes can cause mydriasis and should be kept in mind when evaluating this finding (Table 3).³² If radiographic findings do not suggest elevated intracranial pressure, further workup into these other processes should be pursued.

STATUS EPILEPTICUS: SEIZURE CONTROL IS IMPORTANT

A continuous unremitting seizure lasting longer than 5 minutes or recurrent seizure activity in a patient who does not regain consciousness between seizures should be treated as status epilepticus. All seizure types carry the risk of progressing to status epilepticus, and responsiveness to antiepileptic drug therapy is inversely related to the duration of seizures. It is imperative that seizure activity be treated early and aggressively to prevent recalcitrant seizure activity, neuronal damage, and progression to status epilepticus.³³

Once the ABCs of emergency stabilization have been performed (ie, airway, breathing, circulation), antiepileptic drug therapy should start immediately using established algorithms (Figure 1).^34–36 During the course of treatment, the reliability of the neurologic examination may be limited due to medication effects or continued status epilepticus, making continuous video electroencephalographic monitoring often necessary to guide further therapy in patients who are not rapidly recovering.^34–38

Once status epilepticus has resolved, further investigation into the underlying cause should be pursued quickly, especially in patients without a previous diagnosis of epilepsy. Head CT with contrast or magnetic resonance imaging can be used to look for any structural abnormality that may explain seizures. Basic laboratory tests including toxicology screening can identify a common trigger such as hypoglycemia or stimulant use. Fever or other possible signs of meningitis should be investigated further with cerebrospinal fluid analysis.

SPINAL CORD INJURY

Acute spinal cord injury can lead to substantial long-term neurologic impairment and should be suspected in any patient presenting with focal motor loss, sensory loss, or both with sparing of the cranial nerves and mental status. Causes of injury include compression (traumatic or nontraumatic) and inflammatory and noninflammatory myelopathies.

The location of the injury can be inferred by analyzing the symptoms, which can point to the cord level and indicate whether the anterior or posterior of the cord is involved. Anterior cord injury tends to affect the descending corticospinal and pyramidal tracts, resulting in motor deficits and weakness. Posterior cord injury involves the dorsal columns, leading to deficits of vibration sensation and proprioception. High cervical cord injuries tend to involve varying degrees of quadriparesis, sensory loss, and sometimes respiratory compromise. A clinical history of bilateral lower-extremity weakness, a “band-like” sensory complaint around the lower chest or abdomen, or both, can suggest thoracic cord involvement. Symptoms isolated to one or both lower extremities along with lower back pain and bowel or bladder involvement may point to injury of the lumbosacral cord.

Basic management of spinal cord injury includes decompression of the bladder and initial protection against further injury with a stabilizing collar or brace.

Magnetic resonance imaging with and without contrast is the ideal study to evaluate injuries to the spinal cord itself. While CT is helpful in identifying bony disease of the spinal column (eg, evaluating traumatic fractures), it is not helpful in viewing intrinsic cord pathology.

Traumatic myelopathy

Traumatic spinal cord injury is usually suggested by the clinical history and confirmed with CT. In this setting, early consultation with a neurosurgeon is required to prevent permanent cord injury.

Guidelines suggest maintaining a mean arterial pressure greater than 85 to 90 mm Hg for the first 7 days after traumatic spinal cord injury, a particular problem in the setting of hemodynamic instability, which can accompany lesions above the midthoracic level.^39,40

Patients with vertebral body misalignment should be placed in an appropriate stabilizing collar or brace until a medically trained professional deems it appropriate to discontinue the device, or until surgical stabilization is performed.

Methylprednisone is a controversial intervention for acute spinal cord trauma, lacking clear benefit in meta-analyses.⁴¹

Nontraumatic compressive myelopathy

Patients with nontraumatic compressive myelopathy tend to present with varying degrees of back pain and worsening sensorimotor function. The differential diagnosis includes epidural abscesses, hematoma, metastatic neoplasm, and osteophyte compression (Table 4). The clinical history helps to guide therapy and should involve assessment for previous spinal column injury, immunocompromised state, travel history (which provides information on risks of exposure to a variety of diseases, including infections), and constitutional symptoms such as fever and weight loss.

Epidural abscess can have devastating results if missed. Red flags such as recent illness, intravenous drug use, focal back pain, fever, worsening numbness or weakness, and bowel or bladder incontinence should raise suspicion of this disorder. Emergency magnetic resonance imaging is required to diagnose this condition, and treatment involves urgent administration of antibiotics and consideration of surgical drainage.

Noncompressive myelopathies

There are numerous causes of noncompressive spinal cord injury (Table 4), and the etiology may be inflammatory (eg, “myelitis”) or noninflammatory. The diagnostic workup may require both magnetic resonance imaging and cerebrospinal fluid analysis. Acute disease-targeted therapy is rarely indicated and can be deferred until a full diagnostic workup has been completed.

NEUROMUSCULAR DISEASE: IS VENTILATION NEEDED?

Diseases involving the motor components of the peripheral nervous system (Table 5) share the common risk of causing ventilatory failure due to weakness of the diaphragm, intercostal muscles, and upper-airway muscles. Clinicians need to be aware of this risk and view these disorders as neurologic emergencies.

Determining when these patients require mechanical intubation is a challenge. Serial measurements of maximum inspiratory force and vital capacity are important and can be accomplished quickly at the bedside by a respiratory therapist. A maximum inspiratory force less than –30 cm H₂O or a vital capacity less than 20 mL/kg, or both, are worrisome markers that raise concern for impending ventilatory failure. Serial measurements can detect changes in these values that might indicate the need for elective intubation. In any patient presenting with weakness of the limbs, these measurements are an important step in the initial evaluation.

Myasthenic crisis

Myasthenia gravis is caused by autoantibodies directed against postsynaptic acetylcholine receptors. Patients demonstrate muscle weakness, usually in a proximal pattern, with fatigue, respiratory distress, nasal speech, ophthalmoparesis, and dysphagia. Exacerbations can occur as a response to recent infection, surgery, or medications such as neuromuscular blocking agents or aminoglycosides.

Myasthenic crisis, while uncommon, is a life-threatening emergency characterized by bulbar or respiratory failure secondary to muscle weakness. It can occur in patients already diagnosed with myasthenia gravis or may be the initial manifestation of the disease.^42–49 Intubation and mechanical ventilation are frequently required. Postoperative myasthenic patients in whom extubation has been delayed more than 24 hours should be considered in crisis.⁴⁵

The diagnosis of myasthenia gravis can be made by serum autoantibody testing, electromyography, and nerve conduction studies (with repetitive stimulation) or administration of edrophonium in patients with obvious ptosis.

The mainstay of therapy for myasthenic crisis is either intravenous immunoglobulin at a dose of 2 g/kg over 2 to 5 days or plasmapheresis (5–7 exchanges over 7–14 days). Corticosteroids are not recommended in myasthenic crisis in patients who are not intubated, as they can potentiate an initial worsening of crisis. Once the patient begins to show clinical improvement, outpatient pyridostigmine and immunosuppressive medications can be resumed at a low dose and titrated as tolerated.

Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome)

Acute inflammatory demyelinating polyneuropathy is an autoimmune disorder involving autoantibodies against axons or myelin in the peripheral nervous system.

This disease should be suspected in a patient who is developing worsening muscle weakness (usually with areflexia) over the course of days to weeks. Occasionally, a recent diarrheal or other systemic infectious trigger can be identified. Blood pressure instability and cardiac arrhythmia can also be seen due to autonomic nerve involvement. Although classically described as an “ascending paralysis,” other variants of this disease have distinct clinical presentations (eg, the descending paralysis, ataxia, areflexia, ophthalmoparesis of the Miller Fisher syndrome).

Acute inflammatory demyelinating polyneuropathy is diagnosed by electromyography and nerve conduction studies. A cerebrospinal fluid profile demonstrating elevated protein and few white blood cells is typical.

Treatment, as in myasthenic crisis, involves intravenous immunoglobulin or plasmapheresis. Corticosteroids are ineffective. Anticipation of ventilatory failure and expectant intubation is essential, given the progressive nature of the disorder.⁵⁰

Neurologic emergencies such as acute stroke, status epilepticus, subarachnoid hemorrhage, neuromuscular weakness, and spinal cord injury affect millions of Americans yearly.^1,2 These conditions can be difficult to diagnose, and delays in recognition and treatment can have devastating results. Consequently, it is important for nonneurologists to be able to quickly recognize these conditions and initiate timely management, often while awaiting neurologic consultation.

Here, we review how to recognize and treat these common, serious conditions.

ACUTE ISCHEMIC STROKE: TIME IS OF THE ESSENCE

Stroke is the fourth leading cause of death in the United States and is one of the most common causes of disability worldwide.^3–5 About 85% of strokes are ischemic, resulting from diminished vascular supply to the brain. Symptoms such as facial droop, unilateral weakness or numbness, aphasia, gaze deviation, and unsteadiness of gait may be seen. Time is of the essence, as all currently available interventions are safe and effective only within defined time windows.

Diagnosis and assessment

When acute ischemic stroke is suspected, the clinical history, time of onset, and basic neurologic examination should be obtained quickly.

The National Institutes of Health (NIH) stroke scale is an objective marker for assessing stroke severity as well as evolution of disease and should be obtained in all stroke patients. Scores range from 0 (best) to 42 (worst) (www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf).

Time of onset of symptoms is essential to determine, since it guides eligibility for acute therapies. Clinicians should ascertain the last time the patient was seen to be neurologically well in order to estimate this time window as closely as possible.

Laboratory tests should include a fingerstick blood glucose measurement, coagulation studies, complete blood cell count, and basic metabolic profile.

Computed tomography (CT) of the head without contrast should be obtained immediately to exclude acute hemorrhage and any alternative diagnoses that could explain the patient’s symptoms. Acute brain ischemia is often not apparent on CT during the first few hours of injury. Therefore, a patient presenting with new focal neurologic deficits and an unremarkable result on CT of the head should be treated as having had an acute ischemic stroke, and interventional therapies should be considered.

Stroke mimics should be considered and treated, as appropriate (Table 1).

Acute management of ischemic stroke

Acute treatment should not be delayed by obtaining chest radiography, inserting a Foley catheter, or obtaining an electrocardiogram. The longer the time that elapses before treatment, the worse the functional outcome, underscoring the need for rapid decision-making.^6–8

Lowering the head of the bed may provide benefit by promoting blood flow to ischemic brain tissue.⁹ However, this should not be done in patients with significantly elevated intracerebral pressure and concern for herniation.

Permissive hypertension (antihypertensive treatment only for blood pressure greater than 220/110 mm Hg) should be allowed per national guidelines to provide adequate perfusion to brain areas at risk of injury.¹⁰

Tissue plasminogen activator. Patients with ischemic stroke who present within 3 hours of symptom onset should be considered for intravenous administration of tissue plasminogen activator (tPA), a safe and effective therapy with nearly 2 decades of evidence to support its use.¹⁰ The treating physician should carefully review the risks and benefits of this therapy.

To receive tPA, the patient must have all of the following:

• Clinical diagnosis of ischemic stroke with measurable neurologic deficit
• Onset of symptoms within the past 3 hours
• Age 18 or older.

The patient must not have any of the following:

• Significant stroke within the past 3 months
• Severe traumatic head injury within the past 3 months
• History of significant intracerebral hemorrhage
• Previously ruptured arteriovenous malformation or intracranial aneurysm
• Central nervous system neoplasm
• Arterial puncture at a noncompressible site within the past 7 days
• Evidence of hemorrhage on CT of the head
• Evidence of ischemia in greater than 33% of the cerebral hemisphere on head CT
• History and symptoms strongly suggesting subarachnoid hemorrhage
• Persistent hypertension (systolic pressure ≥ 185 mm Hg or diastolic pressure ≥ 110 mm Hg)
• Evidence of acute significant bleeding (external or internal)
• Hypoglycemia—ie, serum glucose less than 50 mg/dL (< 2.8 mmol/L)
• Thrombocytopenia (platelet count < 100 × 10⁹/L)
• Significant coagulopathy (international normalized ratio > 1.7, prothrombin time > 15 seconds, or abnormally elevated activated partial thromboplastin time)
• Current use of a factor Xa inhibitor or direct thrombin inhibitor.

Relative contraindications:

• Minor or rapidly resolving symptoms
• Major surgery or trauma within the past 14 days
• Gastrointestinal or urinary tract bleeding within the past 21 days
• Myocardial infarction in the past 3 months
• Unruptured intracranial aneurysm
• Seizure occurring at stroke onset
• Pregnancy.

If these criteria are satisfied, tPA should be given at a dose of 0.9 mg/kg intravenously over 60 minutes. Ten percent  of the dose should be given as an initial bolus, followed by a constant infusion of the remaining 90% over 1 hour.

If tPA is given, the blood pressure must be kept lower than 185/110 mm Hg to minimize the risk of symptomatic intracerebral hemorrhage.

A subset of patients may benefit from receiving intravenous tPA between 3 and 4.5 hours after the onset of stroke symptoms. These include patients who are no more than 80 years old, who have not recently used oral anticoagulants, who do not have severe neurologic injury (ie, do not have NIH Stroke Scale scores > 25), and who do not have diabetes mellitus or a history of ischemic stroke.¹¹ Although many hospitals have such a protocol for tPA up to 4.5 hours after the onset of stroke symptoms, this time window is not currently approved by the US Food and Drug Administration.

Intra-arterial therapy. Based on recent trials, some patients may benefit further from intra-arterial thrombolysis or mechanical thrombectomy, both delivered during catheter-based cerebral angiography, independent of intravenous tPA administration.^12,13 These patients should be evaluated on a case-by-case basis by a neurologist and neurointerventional team. Time windows for these treatments generally extend to 6 hours from stroke onset and perhaps even longer in some situations (eg, basilar artery occlusion).

An antiplatelet agent should be started quickly in all stroke patients who do not receive tPA. Patients who receive tPA can begin receiving an antiplatelet agent 24 hours afterward.

Unfractionated heparin. There is no evidence to support the use of unfractionated heparin in most cases of acute ischemic stroke.¹⁰

Glucose control (in the range of 140–180 mg/dL) and fever control remain essential elements of post-acute stroke care to provide additional protection to the damaged brain.

For ischemic stroke due to atrial fibrillation

In ischemic stroke due to atrial fibrillation, early anticoagulation should be considered, based on the CHA₂DS₂-VASC risk of ischemic stroke vs the HAS-BLED risk of hemorrhage (calculators available at www.mdcalc.com).

In general, anticoagulation may be withheld during the first 72 hours while further stroke workup and evaluation of extent of injury are carried out, as there is an increased risk of hemorrhagic transformation of the ischemic stroke. Often, anticoagulation is resumed at a full dose between 72 hours and 2 weeks of the ischemic stroke.

ACUTE HEMORRHAGIC STROKE: BLOOD PRESSURE, COAGULATION

Approximately 15% of strokes are caused by intracerebral hemorrhage, which can be detected with noncontrast head CT with a sensitivity of 98.6% within 6 hours of the onset of bleeding.¹⁴ A common underlying cause of intracerebral hemorrhage is chronic poorly controlled hypertension, causing rupture of damaged (or “lipohyalinized”) vessels with resultant blood extravasation into the brain parenchyma. Other causes are less common (Table 2).

Treatment of acute hemorrhagic stroke

Acute treatment of intracerebral hemorrhage includes blood pressure control, reversal of underlying coagulopathy or anticoagulation, and sometimes intracranial pressure control. There is little role for surgery in most cases, based on findings of randomized trials.¹⁵

Blood pressure control. Many studies have investigated optimal blood pressure goals in acute intracerebral hemorrhage. Recent data suggest that early aggressive therapy, targeting a systolic blood pressure goal less than 140 mm Hg within the first hour, is safe and can lead to better functional outcomes than a more conservative blood-pressure-lowering target.¹⁶ Rapid-onset, short-acting antihypertensive agents in intravenous form, such as nicardipine and labetalol, are frequently used. Of note, this treatment strategy for hemorrhagic stroke is in direct contrast to the treatment of ischemic stroke, in which permissive hypertension (blood pressure goal < 220/110 mm Hg) is often pursued.

Reversal of any coagulation abnormalities should be done quickly in intracranial hemorrhage. Warfarin use has been shown to be a strong independent predictor of intracranial hemorrhage expansion, which increases the risk of death.^17,18

Increasingly, agents other than vitamin K or fresh-frozen plasma are being used to rapidly reverse anticoagulation, including prothrombin complex concentrate (available in three- and four-factor preparations) and recombinant factor VIIa. While four-factor prothrombin complex concentrate and recombinant factor VIIa have been shown to be more efficacious than fresh-frozen plasma, there are limited data directly comparing these newer reversal agents against each other.¹⁹ The use of these medications is limited by availability and practitioner familiarity.^20–22

Reversing anticoagulation due to target-specific oral anticoagulants. The acute management of intracranial hemorrhage in patients taking the new target-specific oral anticoagulants (eg, dabigatran, apixaban, rivaroxaban, edoxaban) remains challenging. Laboratory tests such as factor Xa levels are not readily available in many institutions and do not provide results in a timely fashion, and in the interim, acute hemorrhage and clinical deterioration may occur. Management strategies involve giving fresh-frozen plasma, prothrombin complex concentrate, and consideration of hemodialysis.²³ Dabigatran reversal with idarucizumab has recently been shown to have efficacy.²⁴

Vigilance for elevated intracranial pressure. Intracranial hemorrhage can occasionally cause elevated intracranial pressure, which should be treated rapidly. Any acute decline in mental status in a patient with intracranial hemorrhage requires emergency imaging to evaluate for expansion of hemorrhage.

SUBARACHNOID HEMORRHAGE

The sudden onset of a “thunderclap” headache (often described by patients as “the worst headache of my life”) suggests subarachnoid hemorrhage.

In contrast to intracranial hemorrhage, in subarachnoid hemorrhage blood collects mainly in the cerebral spinal fluid-containing spaces surrounding the brain, leading to a higher incidence of hydrocephalus from impaired drainage of cerebrospinal fluid. Nontraumatic subarachnoid hemorrhage is most often caused by rupture of an intracranial aneurysm, which can be a devastating event, with death rates approaching 50%.²⁵

Diagnosis of subarachnoid hemorrhage

Noncontrast CT of the head is the main modality for diagnosing subarachnoid hemorrhage. Blood within the subarachnoid space is demonstrable in 92% of cases if CT is performed within the first 24 hours of hemorrhage, with an initial sensitivity of about 95% within the first 6 hours of onset.^14,26,27 The longer CT is delayed, the lower the sensitivity.

Some studies suggest that a protocol of CT followed by CT angiography can safely exclude aneurysmal subarachnoid hemorrhage and obviate the need for lumbar puncture. However, further research is required to validate this approach.²⁸

Lumbar puncture. If clinical suspicion of subarachnoid hemorrhage remains strong even though initial CT is negative, lumbar puncture must be performed for cerebrospinal fluid analysis.²⁹ Xanthochromia (a yellowish pigmentation of the cerebrospinal fluid due to the degeneration of blood products that occurs within 8 to 12 hours of bleeding) should raise the alarm for subarachnoid hemorrhage; this sign may be present up to 4 weeks after the bleeding event.³⁰

If lumbar puncture is contraindicated, then aneurysmal subarachnoid hemorrhage has not been ruled out, and further neurologic consultation should be pursued.

Management of subarachnoid hemorrhage

Early management of blood pressure for a ruptured intracranial aneurysm follows strategies similar to those for intracranial hemorrhage. Further investigation is rapidly directed toward an underlying vascular malformation, with intracranial vessel imaging such as CT angiography, magnetic resonance angiography, or the gold standard test—catheter-based cerebral angiography.

Aneurysms are treated (or “secured”) either by surgical clipping or by endovascular coiling. Endovascular coiling is preferable in cases in which both can be safely attempted.³¹ If the facility lacks the resources to do these procedures, the patient should be referred to a nearby tertiary care center.

INTRACRANIAL HYPERTENSION: DANGER OF BRAIN HERNIATION

A number of conditions can cause an acute intracranial pressure elevation. The danger of brain herniation requires that therapies be implemented rapidly to prevent catastrophic neurologic injury. In many situations, nonneurologists are the first responders and therefore should be familiar with basic intracranial pressure management.

Initial symptoms of acute rise in intracranial pressure

As intracranial pressure rises, pressure is typically equally distributed throughout the cranial vault, leading to dysfunction of the ascending reticular activating system, which clinically manifests as the inability to stay alert despite varying degrees of noxious stimulation. Progressive cranial neuropathies (often starting with pupillary abnormalities) and coma are often seen in this setting as the upper brainstem begins to be compressed.

Initial assessment and treatment of elevated intracranial pressure

Noncontrast CT of the head is often obtained immediately when acutely elevated intracranial pressure is suspected. If clinical examination and radiographic findings are consistent with intracranial hypertension, prompt measures can be started at the bedside.

Elevate the head of the bed to 30 degrees to promote venous drainage and reduce intracranial pressure. (In contrast, most other hemodynamically unstable patients are placed flat or in the Trendelenburg position.)

Intubation should be done quickly in cases of airway compromise, and hyperventilation should be started with a goal Paco₂ of 30 to 35 mm Hg. This hypocarbic strategy promotes cerebral vasoconstriction and a transient decrease in intracranial pressure.

Hyperosmolar therapy allows for transient intracranial volume decompression and is the mainstay of emergency medical treatment of intracranial hypertension. Mannitol is a hyper­osmolar polysaccharide that promotes osmotic diuresis and removes excessive cerebral water. In the acute setting, it can be given as an intravenous bolus of 1 to 2 g/kg through a peripheral intravenous line, followed by a bolus every 4 to 6 hours. Hypotension can occur after diuresis, and renal function should be closely monitored since frequent mannitol use can promote acute tubular necrosis. In patients who are anuric, the medication is typically not used.

Hypertonic saline (typically 3% sodium chloride, though different concentrations are available) is an alternative that helps draw interstitial fluid into the intravascular space, decreasing cerebral edema and maintaining hemodynamic stability. Relative contraindications include congestive heart failure or renal failure leading to pulmonary edema from volume overload. Hypertonic saline can be given as a bolus or a constant infusion. Some institutions have rapid access to 23.4% saline, which can be given as a 30-mL bolus but typically requires a central venous catheter for rapid infusion.

Comatose patients with radiographic findings of hydrocephalus, epidural or subdural hematoma, or mass effect with midline shift warrant prompt neurosurgical consultation for further surgical measures of intracranial pressure control and monitoring.

The ‘blown’ pupil

The physician should be concerned about elevated intracranial pressure if a patient has mydriasis, ie, an abnormally dilated (“blown”) pupil, which is a worrisome sign in the setting of true intracranial hypertension. However, many different processes can cause mydriasis and should be kept in mind when evaluating this finding (Table 3).³² If radiographic findings do not suggest elevated intracranial pressure, further workup into these other processes should be pursued.

STATUS EPILEPTICUS: SEIZURE CONTROL IS IMPORTANT

A continuous unremitting seizure lasting longer than 5 minutes or recurrent seizure activity in a patient who does not regain consciousness between seizures should be treated as status epilepticus. All seizure types carry the risk of progressing to status epilepticus, and responsiveness to antiepileptic drug therapy is inversely related to the duration of seizures. It is imperative that seizure activity be treated early and aggressively to prevent recalcitrant seizure activity, neuronal damage, and progression to status epilepticus.³³

Once the ABCs of emergency stabilization have been performed (ie, airway, breathing, circulation), antiepileptic drug therapy should start immediately using established algorithms (Figure 1).^34–36 During the course of treatment, the reliability of the neurologic examination may be limited due to medication effects or continued status epilepticus, making continuous video electroencephalographic monitoring often necessary to guide further therapy in patients who are not rapidly recovering.^34–38

Once status epilepticus has resolved, further investigation into the underlying cause should be pursued quickly, especially in patients without a previous diagnosis of epilepsy. Head CT with contrast or magnetic resonance imaging can be used to look for any structural abnormality that may explain seizures. Basic laboratory tests including toxicology screening can identify a common trigger such as hypoglycemia or stimulant use. Fever or other possible signs of meningitis should be investigated further with cerebrospinal fluid analysis.

SPINAL CORD INJURY

Acute spinal cord injury can lead to substantial long-term neurologic impairment and should be suspected in any patient presenting with focal motor loss, sensory loss, or both with sparing of the cranial nerves and mental status. Causes of injury include compression (traumatic or nontraumatic) and inflammatory and noninflammatory myelopathies.

The location of the injury can be inferred by analyzing the symptoms, which can point to the cord level and indicate whether the anterior or posterior of the cord is involved. Anterior cord injury tends to affect the descending corticospinal and pyramidal tracts, resulting in motor deficits and weakness. Posterior cord injury involves the dorsal columns, leading to deficits of vibration sensation and proprioception. High cervical cord injuries tend to involve varying degrees of quadriparesis, sensory loss, and sometimes respiratory compromise. A clinical history of bilateral lower-extremity weakness, a “band-like” sensory complaint around the lower chest or abdomen, or both, can suggest thoracic cord involvement. Symptoms isolated to one or both lower extremities along with lower back pain and bowel or bladder involvement may point to injury of the lumbosacral cord.

Basic management of spinal cord injury includes decompression of the bladder and initial protection against further injury with a stabilizing collar or brace.

Magnetic resonance imaging with and without contrast is the ideal study to evaluate injuries to the spinal cord itself. While CT is helpful in identifying bony disease of the spinal column (eg, evaluating traumatic fractures), it is not helpful in viewing intrinsic cord pathology.

Traumatic myelopathy

Traumatic spinal cord injury is usually suggested by the clinical history and confirmed with CT. In this setting, early consultation with a neurosurgeon is required to prevent permanent cord injury.

Guidelines suggest maintaining a mean arterial pressure greater than 85 to 90 mm Hg for the first 7 days after traumatic spinal cord injury, a particular problem in the setting of hemodynamic instability, which can accompany lesions above the midthoracic level.^39,40

Patients with vertebral body misalignment should be placed in an appropriate stabilizing collar or brace until a medically trained professional deems it appropriate to discontinue the device, or until surgical stabilization is performed.

Methylprednisone is a controversial intervention for acute spinal cord trauma, lacking clear benefit in meta-analyses.⁴¹

Nontraumatic compressive myelopathy

Patients with nontraumatic compressive myelopathy tend to present with varying degrees of back pain and worsening sensorimotor function. The differential diagnosis includes epidural abscesses, hematoma, metastatic neoplasm, and osteophyte compression (Table 4). The clinical history helps to guide therapy and should involve assessment for previous spinal column injury, immunocompromised state, travel history (which provides information on risks of exposure to a variety of diseases, including infections), and constitutional symptoms such as fever and weight loss.

Epidural abscess can have devastating results if missed. Red flags such as recent illness, intravenous drug use, focal back pain, fever, worsening numbness or weakness, and bowel or bladder incontinence should raise suspicion of this disorder. Emergency magnetic resonance imaging is required to diagnose this condition, and treatment involves urgent administration of antibiotics and consideration of surgical drainage.

Noncompressive myelopathies

There are numerous causes of noncompressive spinal cord injury (Table 4), and the etiology may be inflammatory (eg, “myelitis”) or noninflammatory. The diagnostic workup may require both magnetic resonance imaging and cerebrospinal fluid analysis. Acute disease-targeted therapy is rarely indicated and can be deferred until a full diagnostic workup has been completed.

NEUROMUSCULAR DISEASE: IS VENTILATION NEEDED?

Diseases involving the motor components of the peripheral nervous system (Table 5) share the common risk of causing ventilatory failure due to weakness of the diaphragm, intercostal muscles, and upper-airway muscles. Clinicians need to be aware of this risk and view these disorders as neurologic emergencies.

Determining when these patients require mechanical intubation is a challenge. Serial measurements of maximum inspiratory force and vital capacity are important and can be accomplished quickly at the bedside by a respiratory therapist. A maximum inspiratory force less than –30 cm H₂O or a vital capacity less than 20 mL/kg, or both, are worrisome markers that raise concern for impending ventilatory failure. Serial measurements can detect changes in these values that might indicate the need for elective intubation. In any patient presenting with weakness of the limbs, these measurements are an important step in the initial evaluation.

Myasthenic crisis

Myasthenia gravis is caused by autoantibodies directed against postsynaptic acetylcholine receptors. Patients demonstrate muscle weakness, usually in a proximal pattern, with fatigue, respiratory distress, nasal speech, ophthalmoparesis, and dysphagia. Exacerbations can occur as a response to recent infection, surgery, or medications such as neuromuscular blocking agents or aminoglycosides.

Myasthenic crisis, while uncommon, is a life-threatening emergency characterized by bulbar or respiratory failure secondary to muscle weakness. It can occur in patients already diagnosed with myasthenia gravis or may be the initial manifestation of the disease.^42–49 Intubation and mechanical ventilation are frequently required. Postoperative myasthenic patients in whom extubation has been delayed more than 24 hours should be considered in crisis.⁴⁵

The diagnosis of myasthenia gravis can be made by serum autoantibody testing, electromyography, and nerve conduction studies (with repetitive stimulation) or administration of edrophonium in patients with obvious ptosis.

The mainstay of therapy for myasthenic crisis is either intravenous immunoglobulin at a dose of 2 g/kg over 2 to 5 days or plasmapheresis (5–7 exchanges over 7–14 days). Corticosteroids are not recommended in myasthenic crisis in patients who are not intubated, as they can potentiate an initial worsening of crisis. Once the patient begins to show clinical improvement, outpatient pyridostigmine and immunosuppressive medications can be resumed at a low dose and titrated as tolerated.

Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome)

Acute inflammatory demyelinating polyneuropathy is an autoimmune disorder involving autoantibodies against axons or myelin in the peripheral nervous system.

This disease should be suspected in a patient who is developing worsening muscle weakness (usually with areflexia) over the course of days to weeks. Occasionally, a recent diarrheal or other systemic infectious trigger can be identified. Blood pressure instability and cardiac arrhythmia can also be seen due to autonomic nerve involvement. Although classically described as an “ascending paralysis,” other variants of this disease have distinct clinical presentations (eg, the descending paralysis, ataxia, areflexia, ophthalmoparesis of the Miller Fisher syndrome).

Acute inflammatory demyelinating polyneuropathy is diagnosed by electromyography and nerve conduction studies. A cerebrospinal fluid profile demonstrating elevated protein and few white blood cells is typical.

Treatment, as in myasthenic crisis, involves intravenous immunoglobulin or plasmapheresis. Corticosteroids are ineffective. Anticipation of ventilatory failure and expectant intubation is essential, given the progressive nature of the disorder.⁵⁰

SNOWMASS, COLO. – A clear message from the first-ever randomized trial of surgical mitral valve repair versus replacement for patients with severe ischemic mitral regurgitation is that replacement should be utilized more liberally, Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

The results of prosthetic valve implantation proved far more durable than repair. At 2 years of follow-up in this 251-patient multicenter trial conducted by the Cardiothoracic Surgical Trials Network (CSTN), the incidence of recurrent moderate or severe mitral regurgitation was just 3.8% in the valve replacement group, compared with 58.8% with repair via restrictive annuloplasty. As a result, the repair group had significantly more heart failure–related adverse events and cardiovascular hospitalizations and a lower rate of clinically meaningful improvement in quality of life scores, noted Dr. Mack, an investigator in the trial and medical director of the Baylor Health Care System in Plano, Tex.

“I think surgical mitral valve replacement has had a bad name over the years, and one of the reasons is because of the worse left ventricular function afterwards. However, that was a casualty of excising the mitral valve and the subvalvular apparatus, causing atrial-ventricular disconnection. We’ve gotten smarter about this. The techniques we now use are valve sparing,” the cardiothoracic surgeon said.

He was quick to add, however, that the CSTN study results are by no means the death knell for restrictive mitral annuloplasty. Indeed, participants in the mitral valve repair group who didn’t develop recurrent regurgitation actually experienced significant positive reverse remodeling as reflected by improvement in their left ventricular end-systolic volume index, the primary endpoint of the study (N Engl J Med. 2016;374:344-35).

The key to successful outcomes in mitral valve repair is to save the procedure for patients who are unlikely to develop recurrent regurgitation. And a substudy of the CTSN trial led by Dr. Irving L. Kron, professor of surgery at the University of Virginia, Charlottesville, provides practical guidance on that score. The investigators conducted a logistic regression analysis of the mitral valve repair group’s baseline echocardiographic and clinical characteristics and identified a collection of strong predictors of recurrent regurgitation within 2 years (J Thorac Cardiovasc Surg. 2015 Mar;149[3]:752-61).

“The bottom line is, the more tethering you have of the mitral valve leaflets, the more likely you are to have recurrent mitral regurgitation after mitral valve annuloplasty,” Dr. Mack said.

The predictors of recurrent regurgitation included a coaptation depth greater than 10 mm, a posterior leaflet angle in excess of 45 degrees, a distal anterior leaflet angle greater than 25 degrees, inferior basal aneurysm, mitral annular calcification, and a left ventricular end diastolic diameter greater than 65 mm, as well as other indices of advanced left ventricular remodeling.

No or only mild annular dilation, as occurs, for example, in patients whose mitral regurgitation is caused by atrial fibrillation, is another independent predictor of recurrent regurgitation post repair.

“Shrinking the annulus isn’t going to make a difference if the annulus wasn’t dilated to begin with,” the surgeon observed. “If surgery is performed, we now know those patients who are most likely to recur – and they should have mitral valve replacement. If those factors are not present, then repair is still a viable option,” according to Dr. Mack.

That being said, it’s still not known whether correcting severe ischemic mitral regurgitation prolongs life or improves quality of life long term, compared with guideline-directed medical therapy, he stressed.

“Secondary mitral regurgitation is a disease of the left ventricle, not the mitral valve. So it’s possible that mitral regurgitation reduction has no benefit because the regurgitation is a surrogate marker not causally related to outcome. I don’t think so, but it is a possibility,” Dr. Mack conceded.

This is a clinically important unresolved question because secondary mitral regurgitation is extremely common. In a retrospective echocardiographic study of 558 heart failure patients with a left ventricular ejection fraction of 35% or less and class III-IV symptoms, 90% of them had some degree of mitral regurgitation (J Card Fail. 2004 Aug;10[4]:285-91).

Together with Columbia University cardiologist Dr. Gregg W. Stone, Dr. Mack is coprincipal investigator of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, which is expected to provide an answer to this key question. The multicenter U.S. study involves a planned 420 patients with severely symptomatic secondary mitral regurgitation who are deemed at prohibitive risk for surgery. They are to be randomized to guideline-directed medical therapy with or without transcatheter mitral valve repair using the MitraClip device. Enrollment should be completed by May, with initial results available in late 2017.

Dr. Mack reported receiving research grants from Abbott Vascular, which is sponsoring the COAPT trial, as well as from Edwards Lifesciences.

[email protected]

SNOWMASS, COLO. – A clear message from the first-ever randomized trial of surgical mitral valve repair versus replacement for patients with severe ischemic mitral regurgitation is that replacement should be utilized more liberally, Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

The results of prosthetic valve implantation proved far more durable than repair. At 2 years of follow-up in this 251-patient multicenter trial conducted by the Cardiothoracic Surgical Trials Network (CSTN), the incidence of recurrent moderate or severe mitral regurgitation was just 3.8% in the valve replacement group, compared with 58.8% with repair via restrictive annuloplasty. As a result, the repair group had significantly more heart failure–related adverse events and cardiovascular hospitalizations and a lower rate of clinically meaningful improvement in quality of life scores, noted Dr. Mack, an investigator in the trial and medical director of the Baylor Health Care System in Plano, Tex.

“I think surgical mitral valve replacement has had a bad name over the years, and one of the reasons is because of the worse left ventricular function afterwards. However, that was a casualty of excising the mitral valve and the subvalvular apparatus, causing atrial-ventricular disconnection. We’ve gotten smarter about this. The techniques we now use are valve sparing,” the cardiothoracic surgeon said.

He was quick to add, however, that the CSTN study results are by no means the death knell for restrictive mitral annuloplasty. Indeed, participants in the mitral valve repair group who didn’t develop recurrent regurgitation actually experienced significant positive reverse remodeling as reflected by improvement in their left ventricular end-systolic volume index, the primary endpoint of the study (N Engl J Med. 2016;374:344-35).

The key to successful outcomes in mitral valve repair is to save the procedure for patients who are unlikely to develop recurrent regurgitation. And a substudy of the CTSN trial led by Dr. Irving L. Kron, professor of surgery at the University of Virginia, Charlottesville, provides practical guidance on that score. The investigators conducted a logistic regression analysis of the mitral valve repair group’s baseline echocardiographic and clinical characteristics and identified a collection of strong predictors of recurrent regurgitation within 2 years (J Thorac Cardiovasc Surg. 2015 Mar;149[3]:752-61).

“The bottom line is, the more tethering you have of the mitral valve leaflets, the more likely you are to have recurrent mitral regurgitation after mitral valve annuloplasty,” Dr. Mack said.

The predictors of recurrent regurgitation included a coaptation depth greater than 10 mm, a posterior leaflet angle in excess of 45 degrees, a distal anterior leaflet angle greater than 25 degrees, inferior basal aneurysm, mitral annular calcification, and a left ventricular end diastolic diameter greater than 65 mm, as well as other indices of advanced left ventricular remodeling.

No or only mild annular dilation, as occurs, for example, in patients whose mitral regurgitation is caused by atrial fibrillation, is another independent predictor of recurrent regurgitation post repair.

“Shrinking the annulus isn’t going to make a difference if the annulus wasn’t dilated to begin with,” the surgeon observed. “If surgery is performed, we now know those patients who are most likely to recur – and they should have mitral valve replacement. If those factors are not present, then repair is still a viable option,” according to Dr. Mack.

That being said, it’s still not known whether correcting severe ischemic mitral regurgitation prolongs life or improves quality of life long term, compared with guideline-directed medical therapy, he stressed.

“Secondary mitral regurgitation is a disease of the left ventricle, not the mitral valve. So it’s possible that mitral regurgitation reduction has no benefit because the regurgitation is a surrogate marker not causally related to outcome. I don’t think so, but it is a possibility,” Dr. Mack conceded.

This is a clinically important unresolved question because secondary mitral regurgitation is extremely common. In a retrospective echocardiographic study of 558 heart failure patients with a left ventricular ejection fraction of 35% or less and class III-IV symptoms, 90% of them had some degree of mitral regurgitation (J Card Fail. 2004 Aug;10[4]:285-91).

Together with Columbia University cardiologist Dr. Gregg W. Stone, Dr. Mack is coprincipal investigator of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, which is expected to provide an answer to this key question. The multicenter U.S. study involves a planned 420 patients with severely symptomatic secondary mitral regurgitation who are deemed at prohibitive risk for surgery. They are to be randomized to guideline-directed medical therapy with or without transcatheter mitral valve repair using the MitraClip device. Enrollment should be completed by May, with initial results available in late 2017.

Dr. Mack reported receiving research grants from Abbott Vascular, which is sponsoring the COAPT trial, as well as from Edwards Lifesciences.

[email protected]

SNOWMASS, COLO. – A clear message from the first-ever randomized trial of surgical mitral valve repair versus replacement for patients with severe ischemic mitral regurgitation is that replacement should be utilized more liberally, Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

The results of prosthetic valve implantation proved far more durable than repair. At 2 years of follow-up in this 251-patient multicenter trial conducted by the Cardiothoracic Surgical Trials Network (CSTN), the incidence of recurrent moderate or severe mitral regurgitation was just 3.8% in the valve replacement group, compared with 58.8% with repair via restrictive annuloplasty. As a result, the repair group had significantly more heart failure–related adverse events and cardiovascular hospitalizations and a lower rate of clinically meaningful improvement in quality of life scores, noted Dr. Mack, an investigator in the trial and medical director of the Baylor Health Care System in Plano, Tex.

“I think surgical mitral valve replacement has had a bad name over the years, and one of the reasons is because of the worse left ventricular function afterwards. However, that was a casualty of excising the mitral valve and the subvalvular apparatus, causing atrial-ventricular disconnection. We’ve gotten smarter about this. The techniques we now use are valve sparing,” the cardiothoracic surgeon said.

He was quick to add, however, that the CSTN study results are by no means the death knell for restrictive mitral annuloplasty. Indeed, participants in the mitral valve repair group who didn’t develop recurrent regurgitation actually experienced significant positive reverse remodeling as reflected by improvement in their left ventricular end-systolic volume index, the primary endpoint of the study (N Engl J Med. 2016;374:344-35).

The key to successful outcomes in mitral valve repair is to save the procedure for patients who are unlikely to develop recurrent regurgitation. And a substudy of the CTSN trial led by Dr. Irving L. Kron, professor of surgery at the University of Virginia, Charlottesville, provides practical guidance on that score. The investigators conducted a logistic regression analysis of the mitral valve repair group’s baseline echocardiographic and clinical characteristics and identified a collection of strong predictors of recurrent regurgitation within 2 years (J Thorac Cardiovasc Surg. 2015 Mar;149[3]:752-61).

“The bottom line is, the more tethering you have of the mitral valve leaflets, the more likely you are to have recurrent mitral regurgitation after mitral valve annuloplasty,” Dr. Mack said.

The predictors of recurrent regurgitation included a coaptation depth greater than 10 mm, a posterior leaflet angle in excess of 45 degrees, a distal anterior leaflet angle greater than 25 degrees, inferior basal aneurysm, mitral annular calcification, and a left ventricular end diastolic diameter greater than 65 mm, as well as other indices of advanced left ventricular remodeling.

No or only mild annular dilation, as occurs, for example, in patients whose mitral regurgitation is caused by atrial fibrillation, is another independent predictor of recurrent regurgitation post repair.

“Shrinking the annulus isn’t going to make a difference if the annulus wasn’t dilated to begin with,” the surgeon observed. “If surgery is performed, we now know those patients who are most likely to recur – and they should have mitral valve replacement. If those factors are not present, then repair is still a viable option,” according to Dr. Mack.

That being said, it’s still not known whether correcting severe ischemic mitral regurgitation prolongs life or improves quality of life long term, compared with guideline-directed medical therapy, he stressed.

“Secondary mitral regurgitation is a disease of the left ventricle, not the mitral valve. So it’s possible that mitral regurgitation reduction has no benefit because the regurgitation is a surrogate marker not causally related to outcome. I don’t think so, but it is a possibility,” Dr. Mack conceded.

This is a clinically important unresolved question because secondary mitral regurgitation is extremely common. In a retrospective echocardiographic study of 558 heart failure patients with a left ventricular ejection fraction of 35% or less and class III-IV symptoms, 90% of them had some degree of mitral regurgitation (J Card Fail. 2004 Aug;10[4]:285-91).

Together with Columbia University cardiologist Dr. Gregg W. Stone, Dr. Mack is coprincipal investigator of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, which is expected to provide an answer to this key question. The multicenter U.S. study involves a planned 420 patients with severely symptomatic secondary mitral regurgitation who are deemed at prohibitive risk for surgery. They are to be randomized to guideline-directed medical therapy with or without transcatheter mitral valve repair using the MitraClip device. Enrollment should be completed by May, with initial results available in late 2017.

Dr. Mack reported receiving research grants from Abbott Vascular, which is sponsoring the COAPT trial, as well as from Edwards Lifesciences.

[email protected]

CHICAGO – Microsurgery does not cure lymphedema, in most cases. But, in most cases, it does improve the severity of lymphedema and reduce the complications of this chronic and debilitating disease. And “it certainly improves patients’ quality of life,” lymphedema treatment pioneer Dr. David W. Chang said at the 40th annual Northwestern Vascular Symposium.

Surgical treatment for limb lymphedema has come into its own since a lymphovenous shunt was first used in a dog model in 1962, with Dr. Chang and others now anastomosing subdermal lymphatics to subdermal venules less than 0.8 mm in diameter. The rationale behind “super-microsurgery” is that venous pressure is low in the subdermal venules and has minimal back flow, he said.

Patrice Wendling/Frontline Medical News

One of the big problems early on was knowing exactly where the lymphatic vessels were, but newer technology like indocyanine green (ICG) lymphangiography helps visualize functioning lymphatic channels for potential bypass and determine the severity of the disease. Understanding the disease stage is key to selecting the appropriate surgical procedure.

Lymphovenous bypass (LVB) is best in patients with stage 1 or 2 upper extremity lymphedema, while lymph node transfer (LNT) works for patients who are poor candidates for LVB or require combined breast reconstruction, said Dr. Chang, a plastic surgeon with the University of Chicago.

More recently, Dr. Chang has begun combining LVB and LNT, particularly for the more severe cases with stage 3 or 4 upper or lower extremity disease.

In Dr. Chang’s first 100 consecutive LVB cases while at the M.D. Anderson Cancer Center in Houston, quantitative improvement occurred in 74% of patients, symptom improvement in 96%, and the average volume differential reduction was 42% at 12 months (Plast Reconstr Surg. 2013 Nov;132:1305-14). The reduction was significantly larger in patients with earlier stage 1 or 2 vs. later stage 3 or 4 disease (61% vs. 17%).

Images courtesy of Dr. David W. Chang

During lymphovenous bypass, ICG is injected into the dermis of the web space and the superficial lymphatics evaluated with near-infrared fluorescence. It is easy to identify discrete functioning lymphatic channels in early-stage disease, but in late-stage disease significant dermal back flow is present, Dr. Chang said.

Dissection is performed under the microscope in the superficial subcutaneous plane to locate a good venule and lymph channel. Lymphatics are confirmed with isosulfan blue and ICG, and once the bypass site is determined, the lymphatic is anastomosed to the venule using 11-0 or 12-0 nylon, preferably in an end-to-side fashion. It’s thought this creates a more favorable flow pattern for the lymph to empty into the venule than an end-to-end anastomosis, he observed.

After the anastomosis is complete, patency is confirmed with isosulfan blue and ICG and the incision is closed under the microscope to ensure that the delicate anastomosis isn’t damaged. To avoid shear injury to the anastomosis, the limb is wrapped postoperatively for about a month without use of compression garments, he said.

Lymph node transfer (LNT) is increasingly being offered at centers to provide relief from lymphedema, although the mechanism by which it works is yet unclear; either the healthy lymph nodes act as a sponge to absorb lymphatic fluid or they induce lymphangiogenesis. Experience has shown, however, that rather than just grafting the lymph nodes, they need to be harvested with a vascular pedicle before transfer and anastomosed to the recipient artery and vein, although reconnecting the actual lymphatics may not be necessary, Dr. Chang observed.

Despite its popularity as a donor site, Dr. Chang said he is reluctant to use the groin because of the potential for iatrogenic lymphedema and prefers to harvest the supraclavicular nodes based off the transverse cervical artery. The external jugular vein can be harvested with the nodes if adequate venae comitantes are not present with the artery. Dissection of this flap can be difficult and care should be taken not to injure the lymphatic ducts, he noted.

It is also important to excise all scar tissue in the recipient site as this can impair lymphatic flow and inhibits lymphangiogenesis. If it is difficult to access or remove the scar, the vascularized lymph nodes are best placed just distal on the limb to the site of lymphatic obstruction, he added.

A recent meta-analysis (Plast Reconstr Surg. 2014 Apr;133:905-13) in five LNT studies reported that 91% of patients had a quantitative improvement, 78% discontinued compression garments, and complications were infection (8%), lymphorrhea (15%), and need for additional procedures (36%). There was great heterogeneity between studies, so the results should be interpreted with caution, Dr. Chang advised.

LNT is frequently combined with autologous breast reconstruction in patients with breast cancer, who comprise a significant percentage of Dr. Chang’s practice. The overall incidence of arm lymphedema after breast cancer can range from 8% to 56% at 2 years’ post-surgery, with the risk higher among women undergoing axillary lymph node dissection and/or axillary radiation.

Outcomes with combined LNT and breast reconstruction have been favorable, with one series reporting evidence of improved lymphatic flow on lymphoscintigraphy in five of six cases and one-third of patients no longer needing compression therapy (Ann Surg. 2012 Mar;255:468-73).

In cases where the patient requires a large skin paddle or seeks breast reconstruction after a previous mastectomy, lateral superficial groin lymph nodes can be harvested for transfer, leaving the deeper lymph nodes that drain the leg behind, Dr. Chang said. The nodes are usually clustered at the junction of the superior inferior epigastric and superficial circumflex iliac veins.

When combining LNT with breast reconstruction, this tissue is harvested together with the free abdominal flap used to reconstruct the breast. The superficial circumflex iliac vein is anastomosed in the axilla in addition to the arterial and venous anastomosis of the deep inferior epigastric vessels to the internal mammary vessels for the breast reconstruction. Reverse lymphatic mapping with technetium and ICG is used to decrease the risk of donor site lymphedema.

An algorithmic approach to simultaneous LNT with microvascular breast reconstruction proposed by Dr. Chang resulted in a 47% reduction in mean volume differential 12 months after reconstruction in 29 consecutive patients with refractory lymphedema following breast cancer treatment. These early results also showed no flap losses or donor-site lymphedema and donor-site wound complications in six patients (21%) that resolved with conservative measures (Ann Surg Oncol. 2015 Sep;22:2919-24).

The holy grail may be to strike lymphedema before it develops. To that end, Italian surgeons have proposed the Lymphatic Microsurgical Preventing Healing Approach (LYMPHA), which involves anastomosing arm lymphatics to a collateral branch of the axillary vein at the time of nodal dissection.

Over more than 4 years’ follow-up, only 3 of 74 breast cancer patients who underwent axillary nodal dissection with LYMPHA developed lymphedema, translating into a an exceptionally low 4% risk of lymphedema (Microsurgery. 2014 Sep;34:421-4). However, this approach is controversial because of unknown oncological risk and the uncertainty of its effectiveness in patients who may receive radiation after the surgery, Dr. Chang said in an interview.

Although these techniques show promise, currently no optimal solution exists and more research is needed to better understand lymphatic anatomy and physiology and the pathophysiology of lymphedema, concluded Dr. Chang, who reported no relevant conflicts of interest.

[email protected]

CHICAGO – Microsurgery does not cure lymphedema, in most cases. But, in most cases, it does improve the severity of lymphedema and reduce the complications of this chronic and debilitating disease. And “it certainly improves patients’ quality of life,” lymphedema treatment pioneer Dr. David W. Chang said at the 40th annual Northwestern Vascular Symposium.

Surgical treatment for limb lymphedema has come into its own since a lymphovenous shunt was first used in a dog model in 1962, with Dr. Chang and others now anastomosing subdermal lymphatics to subdermal venules less than 0.8 mm in diameter. The rationale behind “super-microsurgery” is that venous pressure is low in the subdermal venules and has minimal back flow, he said.

Patrice Wendling/Frontline Medical News

One of the big problems early on was knowing exactly where the lymphatic vessels were, but newer technology like indocyanine green (ICG) lymphangiography helps visualize functioning lymphatic channels for potential bypass and determine the severity of the disease. Understanding the disease stage is key to selecting the appropriate surgical procedure.

Lymphovenous bypass (LVB) is best in patients with stage 1 or 2 upper extremity lymphedema, while lymph node transfer (LNT) works for patients who are poor candidates for LVB or require combined breast reconstruction, said Dr. Chang, a plastic surgeon with the University of Chicago.

More recently, Dr. Chang has begun combining LVB and LNT, particularly for the more severe cases with stage 3 or 4 upper or lower extremity disease.

In Dr. Chang’s first 100 consecutive LVB cases while at the M.D. Anderson Cancer Center in Houston, quantitative improvement occurred in 74% of patients, symptom improvement in 96%, and the average volume differential reduction was 42% at 12 months (Plast Reconstr Surg. 2013 Nov;132:1305-14). The reduction was significantly larger in patients with earlier stage 1 or 2 vs. later stage 3 or 4 disease (61% vs. 17%).

Images courtesy of Dr. David W. Chang

During lymphovenous bypass, ICG is injected into the dermis of the web space and the superficial lymphatics evaluated with near-infrared fluorescence. It is easy to identify discrete functioning lymphatic channels in early-stage disease, but in late-stage disease significant dermal back flow is present, Dr. Chang said.

Dissection is performed under the microscope in the superficial subcutaneous plane to locate a good venule and lymph channel. Lymphatics are confirmed with isosulfan blue and ICG, and once the bypass site is determined, the lymphatic is anastomosed to the venule using 11-0 or 12-0 nylon, preferably in an end-to-side fashion. It’s thought this creates a more favorable flow pattern for the lymph to empty into the venule than an end-to-end anastomosis, he observed.

After the anastomosis is complete, patency is confirmed with isosulfan blue and ICG and the incision is closed under the microscope to ensure that the delicate anastomosis isn’t damaged. To avoid shear injury to the anastomosis, the limb is wrapped postoperatively for about a month without use of compression garments, he said.

Lymph node transfer (LNT) is increasingly being offered at centers to provide relief from lymphedema, although the mechanism by which it works is yet unclear; either the healthy lymph nodes act as a sponge to absorb lymphatic fluid or they induce lymphangiogenesis. Experience has shown, however, that rather than just grafting the lymph nodes, they need to be harvested with a vascular pedicle before transfer and anastomosed to the recipient artery and vein, although reconnecting the actual lymphatics may not be necessary, Dr. Chang observed.

Despite its popularity as a donor site, Dr. Chang said he is reluctant to use the groin because of the potential for iatrogenic lymphedema and prefers to harvest the supraclavicular nodes based off the transverse cervical artery. The external jugular vein can be harvested with the nodes if adequate venae comitantes are not present with the artery. Dissection of this flap can be difficult and care should be taken not to injure the lymphatic ducts, he noted.

It is also important to excise all scar tissue in the recipient site as this can impair lymphatic flow and inhibits lymphangiogenesis. If it is difficult to access or remove the scar, the vascularized lymph nodes are best placed just distal on the limb to the site of lymphatic obstruction, he added.

A recent meta-analysis (Plast Reconstr Surg. 2014 Apr;133:905-13) in five LNT studies reported that 91% of patients had a quantitative improvement, 78% discontinued compression garments, and complications were infection (8%), lymphorrhea (15%), and need for additional procedures (36%). There was great heterogeneity between studies, so the results should be interpreted with caution, Dr. Chang advised.

LNT is frequently combined with autologous breast reconstruction in patients with breast cancer, who comprise a significant percentage of Dr. Chang’s practice. The overall incidence of arm lymphedema after breast cancer can range from 8% to 56% at 2 years’ post-surgery, with the risk higher among women undergoing axillary lymph node dissection and/or axillary radiation.

Outcomes with combined LNT and breast reconstruction have been favorable, with one series reporting evidence of improved lymphatic flow on lymphoscintigraphy in five of six cases and one-third of patients no longer needing compression therapy (Ann Surg. 2012 Mar;255:468-73).

In cases where the patient requires a large skin paddle or seeks breast reconstruction after a previous mastectomy, lateral superficial groin lymph nodes can be harvested for transfer, leaving the deeper lymph nodes that drain the leg behind, Dr. Chang said. The nodes are usually clustered at the junction of the superior inferior epigastric and superficial circumflex iliac veins.

When combining LNT with breast reconstruction, this tissue is harvested together with the free abdominal flap used to reconstruct the breast. The superficial circumflex iliac vein is anastomosed in the axilla in addition to the arterial and venous anastomosis of the deep inferior epigastric vessels to the internal mammary vessels for the breast reconstruction. Reverse lymphatic mapping with technetium and ICG is used to decrease the risk of donor site lymphedema.

An algorithmic approach to simultaneous LNT with microvascular breast reconstruction proposed by Dr. Chang resulted in a 47% reduction in mean volume differential 12 months after reconstruction in 29 consecutive patients with refractory lymphedema following breast cancer treatment. These early results also showed no flap losses or donor-site lymphedema and donor-site wound complications in six patients (21%) that resolved with conservative measures (Ann Surg Oncol. 2015 Sep;22:2919-24).

The holy grail may be to strike lymphedema before it develops. To that end, Italian surgeons have proposed the Lymphatic Microsurgical Preventing Healing Approach (LYMPHA), which involves anastomosing arm lymphatics to a collateral branch of the axillary vein at the time of nodal dissection.

Over more than 4 years’ follow-up, only 3 of 74 breast cancer patients who underwent axillary nodal dissection with LYMPHA developed lymphedema, translating into a an exceptionally low 4% risk of lymphedema (Microsurgery. 2014 Sep;34:421-4). However, this approach is controversial because of unknown oncological risk and the uncertainty of its effectiveness in patients who may receive radiation after the surgery, Dr. Chang said in an interview.

Although these techniques show promise, currently no optimal solution exists and more research is needed to better understand lymphatic anatomy and physiology and the pathophysiology of lymphedema, concluded Dr. Chang, who reported no relevant conflicts of interest.

[email protected]

CHICAGO – Microsurgery does not cure lymphedema, in most cases. But, in most cases, it does improve the severity of lymphedema and reduce the complications of this chronic and debilitating disease. And “it certainly improves patients’ quality of life,” lymphedema treatment pioneer Dr. David W. Chang said at the 40th annual Northwestern Vascular Symposium.

Surgical treatment for limb lymphedema has come into its own since a lymphovenous shunt was first used in a dog model in 1962, with Dr. Chang and others now anastomosing subdermal lymphatics to subdermal venules less than 0.8 mm in diameter. The rationale behind “super-microsurgery” is that venous pressure is low in the subdermal venules and has minimal back flow, he said.

Patrice Wendling/Frontline Medical News

One of the big problems early on was knowing exactly where the lymphatic vessels were, but newer technology like indocyanine green (ICG) lymphangiography helps visualize functioning lymphatic channels for potential bypass and determine the severity of the disease. Understanding the disease stage is key to selecting the appropriate surgical procedure.

Lymphovenous bypass (LVB) is best in patients with stage 1 or 2 upper extremity lymphedema, while lymph node transfer (LNT) works for patients who are poor candidates for LVB or require combined breast reconstruction, said Dr. Chang, a plastic surgeon with the University of Chicago.

More recently, Dr. Chang has begun combining LVB and LNT, particularly for the more severe cases with stage 3 or 4 upper or lower extremity disease.

In Dr. Chang’s first 100 consecutive LVB cases while at the M.D. Anderson Cancer Center in Houston, quantitative improvement occurred in 74% of patients, symptom improvement in 96%, and the average volume differential reduction was 42% at 12 months (Plast Reconstr Surg. 2013 Nov;132:1305-14). The reduction was significantly larger in patients with earlier stage 1 or 2 vs. later stage 3 or 4 disease (61% vs. 17%).

Images courtesy of Dr. David W. Chang

During lymphovenous bypass, ICG is injected into the dermis of the web space and the superficial lymphatics evaluated with near-infrared fluorescence. It is easy to identify discrete functioning lymphatic channels in early-stage disease, but in late-stage disease significant dermal back flow is present, Dr. Chang said.

Dissection is performed under the microscope in the superficial subcutaneous plane to locate a good venule and lymph channel. Lymphatics are confirmed with isosulfan blue and ICG, and once the bypass site is determined, the lymphatic is anastomosed to the venule using 11-0 or 12-0 nylon, preferably in an end-to-side fashion. It’s thought this creates a more favorable flow pattern for the lymph to empty into the venule than an end-to-end anastomosis, he observed.

After the anastomosis is complete, patency is confirmed with isosulfan blue and ICG and the incision is closed under the microscope to ensure that the delicate anastomosis isn’t damaged. To avoid shear injury to the anastomosis, the limb is wrapped postoperatively for about a month without use of compression garments, he said.

Lymph node transfer (LNT) is increasingly being offered at centers to provide relief from lymphedema, although the mechanism by which it works is yet unclear; either the healthy lymph nodes act as a sponge to absorb lymphatic fluid or they induce lymphangiogenesis. Experience has shown, however, that rather than just grafting the lymph nodes, they need to be harvested with a vascular pedicle before transfer and anastomosed to the recipient artery and vein, although reconnecting the actual lymphatics may not be necessary, Dr. Chang observed.

Despite its popularity as a donor site, Dr. Chang said he is reluctant to use the groin because of the potential for iatrogenic lymphedema and prefers to harvest the supraclavicular nodes based off the transverse cervical artery. The external jugular vein can be harvested with the nodes if adequate venae comitantes are not present with the artery. Dissection of this flap can be difficult and care should be taken not to injure the lymphatic ducts, he noted.

It is also important to excise all scar tissue in the recipient site as this can impair lymphatic flow and inhibits lymphangiogenesis. If it is difficult to access or remove the scar, the vascularized lymph nodes are best placed just distal on the limb to the site of lymphatic obstruction, he added.

A recent meta-analysis (Plast Reconstr Surg. 2014 Apr;133:905-13) in five LNT studies reported that 91% of patients had a quantitative improvement, 78% discontinued compression garments, and complications were infection (8%), lymphorrhea (15%), and need for additional procedures (36%). There was great heterogeneity between studies, so the results should be interpreted with caution, Dr. Chang advised.

LNT is frequently combined with autologous breast reconstruction in patients with breast cancer, who comprise a significant percentage of Dr. Chang’s practice. The overall incidence of arm lymphedema after breast cancer can range from 8% to 56% at 2 years’ post-surgery, with the risk higher among women undergoing axillary lymph node dissection and/or axillary radiation.

Outcomes with combined LNT and breast reconstruction have been favorable, with one series reporting evidence of improved lymphatic flow on lymphoscintigraphy in five of six cases and one-third of patients no longer needing compression therapy (Ann Surg. 2012 Mar;255:468-73).

In cases where the patient requires a large skin paddle or seeks breast reconstruction after a previous mastectomy, lateral superficial groin lymph nodes can be harvested for transfer, leaving the deeper lymph nodes that drain the leg behind, Dr. Chang said. The nodes are usually clustered at the junction of the superior inferior epigastric and superficial circumflex iliac veins.

When combining LNT with breast reconstruction, this tissue is harvested together with the free abdominal flap used to reconstruct the breast. The superficial circumflex iliac vein is anastomosed in the axilla in addition to the arterial and venous anastomosis of the deep inferior epigastric vessels to the internal mammary vessels for the breast reconstruction. Reverse lymphatic mapping with technetium and ICG is used to decrease the risk of donor site lymphedema.

An algorithmic approach to simultaneous LNT with microvascular breast reconstruction proposed by Dr. Chang resulted in a 47% reduction in mean volume differential 12 months after reconstruction in 29 consecutive patients with refractory lymphedema following breast cancer treatment. These early results also showed no flap losses or donor-site lymphedema and donor-site wound complications in six patients (21%) that resolved with conservative measures (Ann Surg Oncol. 2015 Sep;22:2919-24).

The holy grail may be to strike lymphedema before it develops. To that end, Italian surgeons have proposed the Lymphatic Microsurgical Preventing Healing Approach (LYMPHA), which involves anastomosing arm lymphatics to a collateral branch of the axillary vein at the time of nodal dissection.

Over more than 4 years’ follow-up, only 3 of 74 breast cancer patients who underwent axillary nodal dissection with LYMPHA developed lymphedema, translating into a an exceptionally low 4% risk of lymphedema (Microsurgery. 2014 Sep;34:421-4). However, this approach is controversial because of unknown oncological risk and the uncertainty of its effectiveness in patients who may receive radiation after the surgery, Dr. Chang said in an interview.

Although these techniques show promise, currently no optimal solution exists and more research is needed to better understand lymphatic anatomy and physiology and the pathophysiology of lymphedema, concluded Dr. Chang, who reported no relevant conflicts of interest.

[email protected]

A bilayer matrix used for dermal regeneration and first approved in 1996 as a treatment for third-degree burns is now approved as a treatment for diabetic foot ulcers.

The Integra Dermal Regeneration Template was approved for the new indication based on a study that showed that the matrix device “improved ulcer healing compared to standard diabetic foot ulcer care,” according to a Food and Drug Administration statement announcing the approval on Jan. 7. Specifically, the new indication is for treating “partial and full-thickness neuropathic diabetic foot ulcers that are greater than 6 weeks in duration, with no capsule, tendon or bone exposed, when used in conjunction with standard diabetic ulcer care.”

The product is a dermal-replacement layer that “consists of a porous, three-dimensional matrix, comprised of bovine collagen and chondroitin-6-sulfate,” with a temporary epidermal silicone layer “to provide immediate wound coverage and control moisture loss. … [It] provides an environment for new skin and tissue to regenerate and heal the wound,” according to the agency’s approval summary.

In a multicenter, randomized controlled study, 307 patients were first treated with 0.9% sodium chloride gel, a secondary dressing, and an offloading device for 2 weeks and were then randomized to a treatment or a control group that received continued treatment with the gel. After 16 weeks, 51% of those treated with the device and 32% of those in the control group had healed completely (P = .001). Among those whose wounds healed, the median time to healing was 43 days in the treatment group and 78 days in the control group.

More patients in the control group had severe adverse events (26.8% vs. 15.6%) and moderate adverse events (42.5% vs. 31.8%).The results of the study, funded and sponsored by the manufacturer, were recently published (Wound Repair Regen. 2015;23[6]:891-900).

The product is contraindicated in patients with bovine or chondroitin allergies and in patients with infected wounds.

The manufacturer, Integra LifeSciences, is marketing the device as Integra Omnigraft Dermal Regeneration Matrix for the diabetic foot ulcer indication.

[email protected]

A bilayer matrix used for dermal regeneration and first approved in 1996 as a treatment for third-degree burns is now approved as a treatment for diabetic foot ulcers.

The Integra Dermal Regeneration Template was approved for the new indication based on a study that showed that the matrix device “improved ulcer healing compared to standard diabetic foot ulcer care,” according to a Food and Drug Administration statement announcing the approval on Jan. 7. Specifically, the new indication is for treating “partial and full-thickness neuropathic diabetic foot ulcers that are greater than 6 weeks in duration, with no capsule, tendon or bone exposed, when used in conjunction with standard diabetic ulcer care.”

The product is a dermal-replacement layer that “consists of a porous, three-dimensional matrix, comprised of bovine collagen and chondroitin-6-sulfate,” with a temporary epidermal silicone layer “to provide immediate wound coverage and control moisture loss. … [It] provides an environment for new skin and tissue to regenerate and heal the wound,” according to the agency’s approval summary.

In a multicenter, randomized controlled study, 307 patients were first treated with 0.9% sodium chloride gel, a secondary dressing, and an offloading device for 2 weeks and were then randomized to a treatment or a control group that received continued treatment with the gel. After 16 weeks, 51% of those treated with the device and 32% of those in the control group had healed completely (P = .001). Among those whose wounds healed, the median time to healing was 43 days in the treatment group and 78 days in the control group.

More patients in the control group had severe adverse events (26.8% vs. 15.6%) and moderate adverse events (42.5% vs. 31.8%).The results of the study, funded and sponsored by the manufacturer, were recently published (Wound Repair Regen. 2015;23[6]:891-900).

The product is contraindicated in patients with bovine or chondroitin allergies and in patients with infected wounds.

The manufacturer, Integra LifeSciences, is marketing the device as Integra Omnigraft Dermal Regeneration Matrix for the diabetic foot ulcer indication.

[email protected]

A bilayer matrix used for dermal regeneration and first approved in 1996 as a treatment for third-degree burns is now approved as a treatment for diabetic foot ulcers.

The Integra Dermal Regeneration Template was approved for the new indication based on a study that showed that the matrix device “improved ulcer healing compared to standard diabetic foot ulcer care,” according to a Food and Drug Administration statement announcing the approval on Jan. 7. Specifically, the new indication is for treating “partial and full-thickness neuropathic diabetic foot ulcers that are greater than 6 weeks in duration, with no capsule, tendon or bone exposed, when used in conjunction with standard diabetic ulcer care.”

The product is a dermal-replacement layer that “consists of a porous, three-dimensional matrix, comprised of bovine collagen and chondroitin-6-sulfate,” with a temporary epidermal silicone layer “to provide immediate wound coverage and control moisture loss. … [It] provides an environment for new skin and tissue to regenerate and heal the wound,” according to the agency’s approval summary.

In a multicenter, randomized controlled study, 307 patients were first treated with 0.9% sodium chloride gel, a secondary dressing, and an offloading device for 2 weeks and were then randomized to a treatment or a control group that received continued treatment with the gel. After 16 weeks, 51% of those treated with the device and 32% of those in the control group had healed completely (P = .001). Among those whose wounds healed, the median time to healing was 43 days in the treatment group and 78 days in the control group.

More patients in the control group had severe adverse events (26.8% vs. 15.6%) and moderate adverse events (42.5% vs. 31.8%).The results of the study, funded and sponsored by the manufacturer, were recently published (Wound Repair Regen. 2015;23[6]:891-900).

The product is contraindicated in patients with bovine or chondroitin allergies and in patients with infected wounds.

The manufacturer, Integra LifeSciences, is marketing the device as Integra Omnigraft Dermal Regeneration Matrix for the diabetic foot ulcer indication.

[email protected]

In his physician-coming-of-age novel House of God, published in 1978, Dr. Steven Bergman (aka Sam Shem) presented rules for an intern’s survival devised by the senior resident, the Fat Man. Rule X was that there is no fever if you don’t check the patient’s temperature, implying that if the physician is unaware of an elevated temperature, no “fever workup” is warranted. A fever workup back then was not just a few keystrokes to order a chest x-ray, complete blood cell count, and blood cultures. The intern had to go to the bedside, awaken and examine the patient, draw the blood, perhaps transport the blood samples to the lab, do a urinalysis, and take the patient to the radiology department to get the chest x-ray. There was often little thought to the intern’s action; a fever in the hospital automatically meant there needed to be a fever workup.

A covering senior resident might have gotten the same notification of a fever, quickly reviewed the chart, gone to the bedside, and assessed whether a bacterial infection was likely enough to warrant the time and annoyance of a full fever workup. As supervising faculty, I will accept that assessment from a senior resident in June more willingly than from an intern in July. Tests and physical findings must be evaluated in context, taking into consideration the patient as well as the skill and experience of the physician.

So how should we react to guidelines that seem to be based on the premise that a positive finding will result in reflexive ordering of additional tests or initiating a therapeutic intervention, and thus should be avoided by all of us—young intern and senior cardiologist alike?

In this issue of the Journal, Dr. Aldo Schenone et al discuss the management of the asymptomatic patient who has carotid artery stenosis. They put into perspective the risks and benefits of medical or surgical intervention as initially defined by several landmark trials, noting how those conclusions should now be modified by knowledge of the efficacy of current medical therapy.

The US Preventive Services Task Force (USPSTF)¹ has recommended against screening for asymptomatic carotid artery stenosis in the general population, noting the limited sensitivity (71%) and specificity (98%) of auscultation to diagnose significant stenosis and lumping it with other ineffective screening tests. In other words, we should not examine asymptomatic patients for carotid bruits, just as we should not look for the fever because finding it could lead to additional testing and potentially unnecessary therapy.

But there are broader implications when a bruit is discovered, beyond simply trodding the algorithmic path toward stenting or endarterectomy. A bruit can suggest occult atherosclerotic disease that warrants medical attention, even if traditional risk factors for atherosclerosis are not prominent. Its discovery can be a wake-up call to the patient (and physician) that the hackneyed admonitions to eat healthy, lose weight, and exercise are actually relevant. Its discovery may lead to medical intervention with a potent statin or with a more aggressive target for blood pressure control. It may color the interpretation of the patient’s described vague arm tingling when bowling.

I may well be misleading myself, but I am more comfortable in dealing with whatever oddities I discover on a physical examination than not doing the examination at all. I’d rather know about the bruit (or the fever) and then think about our options. The stethoscope indeed has limited test reliability, but the real action takes place between its earpieces; the bruit is merely the catalyst for thought. There must be a guideline somewhere that says that a thoughtful, informed, commonsense evaluation is a useful contributor to patient care.

In his physician-coming-of-age novel House of God, published in 1978, Dr. Steven Bergman (aka Sam Shem) presented rules for an intern’s survival devised by the senior resident, the Fat Man. Rule X was that there is no fever if you don’t check the patient’s temperature, implying that if the physician is unaware of an elevated temperature, no “fever workup” is warranted. A fever workup back then was not just a few keystrokes to order a chest x-ray, complete blood cell count, and blood cultures. The intern had to go to the bedside, awaken and examine the patient, draw the blood, perhaps transport the blood samples to the lab, do a urinalysis, and take the patient to the radiology department to get the chest x-ray. There was often little thought to the intern’s action; a fever in the hospital automatically meant there needed to be a fever workup.

A covering senior resident might have gotten the same notification of a fever, quickly reviewed the chart, gone to the bedside, and assessed whether a bacterial infection was likely enough to warrant the time and annoyance of a full fever workup. As supervising faculty, I will accept that assessment from a senior resident in June more willingly than from an intern in July. Tests and physical findings must be evaluated in context, taking into consideration the patient as well as the skill and experience of the physician.

So how should we react to guidelines that seem to be based on the premise that a positive finding will result in reflexive ordering of additional tests or initiating a therapeutic intervention, and thus should be avoided by all of us—young intern and senior cardiologist alike?

In this issue of the Journal, Dr. Aldo Schenone et al discuss the management of the asymptomatic patient who has carotid artery stenosis. They put into perspective the risks and benefits of medical or surgical intervention as initially defined by several landmark trials, noting how those conclusions should now be modified by knowledge of the efficacy of current medical therapy.

The US Preventive Services Task Force (USPSTF)¹ has recommended against screening for asymptomatic carotid artery stenosis in the general population, noting the limited sensitivity (71%) and specificity (98%) of auscultation to diagnose significant stenosis and lumping it with other ineffective screening tests. In other words, we should not examine asymptomatic patients for carotid bruits, just as we should not look for the fever because finding it could lead to additional testing and potentially unnecessary therapy.

But there are broader implications when a bruit is discovered, beyond simply trodding the algorithmic path toward stenting or endarterectomy. A bruit can suggest occult atherosclerotic disease that warrants medical attention, even if traditional risk factors for atherosclerosis are not prominent. Its discovery can be a wake-up call to the patient (and physician) that the hackneyed admonitions to eat healthy, lose weight, and exercise are actually relevant. Its discovery may lead to medical intervention with a potent statin or with a more aggressive target for blood pressure control. It may color the interpretation of the patient’s described vague arm tingling when bowling.

I may well be misleading myself, but I am more comfortable in dealing with whatever oddities I discover on a physical examination than not doing the examination at all. I’d rather know about the bruit (or the fever) and then think about our options. The stethoscope indeed has limited test reliability, but the real action takes place between its earpieces; the bruit is merely the catalyst for thought. There must be a guideline somewhere that says that a thoughtful, informed, commonsense evaluation is a useful contributor to patient care.

In his physician-coming-of-age novel House of God, published in 1978, Dr. Steven Bergman (aka Sam Shem) presented rules for an intern’s survival devised by the senior resident, the Fat Man. Rule X was that there is no fever if you don’t check the patient’s temperature, implying that if the physician is unaware of an elevated temperature, no “fever workup” is warranted. A fever workup back then was not just a few keystrokes to order a chest x-ray, complete blood cell count, and blood cultures. The intern had to go to the bedside, awaken and examine the patient, draw the blood, perhaps transport the blood samples to the lab, do a urinalysis, and take the patient to the radiology department to get the chest x-ray. There was often little thought to the intern’s action; a fever in the hospital automatically meant there needed to be a fever workup.

A covering senior resident might have gotten the same notification of a fever, quickly reviewed the chart, gone to the bedside, and assessed whether a bacterial infection was likely enough to warrant the time and annoyance of a full fever workup. As supervising faculty, I will accept that assessment from a senior resident in June more willingly than from an intern in July. Tests and physical findings must be evaluated in context, taking into consideration the patient as well as the skill and experience of the physician.

So how should we react to guidelines that seem to be based on the premise that a positive finding will result in reflexive ordering of additional tests or initiating a therapeutic intervention, and thus should be avoided by all of us—young intern and senior cardiologist alike?

In this issue of the Journal, Dr. Aldo Schenone et al discuss the management of the asymptomatic patient who has carotid artery stenosis. They put into perspective the risks and benefits of medical or surgical intervention as initially defined by several landmark trials, noting how those conclusions should now be modified by knowledge of the efficacy of current medical therapy.

The US Preventive Services Task Force (USPSTF)¹ has recommended against screening for asymptomatic carotid artery stenosis in the general population, noting the limited sensitivity (71%) and specificity (98%) of auscultation to diagnose significant stenosis and lumping it with other ineffective screening tests. In other words, we should not examine asymptomatic patients for carotid bruits, just as we should not look for the fever because finding it could lead to additional testing and potentially unnecessary therapy.

But there are broader implications when a bruit is discovered, beyond simply trodding the algorithmic path toward stenting or endarterectomy. A bruit can suggest occult atherosclerotic disease that warrants medical attention, even if traditional risk factors for atherosclerosis are not prominent. Its discovery can be a wake-up call to the patient (and physician) that the hackneyed admonitions to eat healthy, lose weight, and exercise are actually relevant. Its discovery may lead to medical intervention with a potent statin or with a more aggressive target for blood pressure control. It may color the interpretation of the patient’s described vague arm tingling when bowling.

I may well be misleading myself, but I am more comfortable in dealing with whatever oddities I discover on a physical examination than not doing the examination at all. I’d rather know about the bruit (or the fever) and then think about our options. The stethoscope indeed has limited test reliability, but the real action takes place between its earpieces; the bruit is merely the catalyst for thought. There must be a guideline somewhere that says that a thoughtful, informed, commonsense evaluation is a useful contributor to patient care.